International Conference on
Nuclear Medicine and Radiation Therapy
Scientific Program
Keynote Session:
Title: The power of precision oncology using PSMA radioligand therapy of metastatic prostate cancer: Theranostics experience in over 800 treatments since 2013
Biography:
Richard Baum is the Chairman and Clinical Director at the Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Germany. He is a renowned Professor of Nuclear Medicine, with several accolades to his credit. He has won numerous awards for his contribution to the field of Nuclear Medicine. He has published over 150 articles in reputed journals and is actively associated with major Nuclear Medicine societies around the world. He was the past president (2013) of the World Association of Radionuclide and Molecular Therapy (WARMTH). His work focusses on Prostate Cancer, Neuroendocrine Tumors, Theranostics and Personalized Medicine.
Abstract:
Navigating the revolution of PSMA radioligand therapy of metastatic prostate cancer: Theranostics experience in over 800 treatments since 2013
Richard P. Baum, Harshad R. Kulkarni, Aviral Singh, Thomas Langbein, Christiane Schuchardt, Jingjing Zhang and Coline Lehmann
Theranostics Center for Molecular Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Zentralklinik Bad Berka, Germany
177Lu-DOTAGA PSMA I & T
Based on the principles of targeted radionuclide therapy, 177Lu labeled ligands binding specific to PSMA were developed using DOTAGA as chelator (Weineisen M et al. 2015). PSMA radioligand therapy (PRLT) with 177Lu-DOTAGA PSMA ligands was performed in 56 progressive, metastasized, castrate-resistant prostate cancer (mCRPC) patients (Baum et al. 2016). Ga-68 PSMA PET/CT was used for patient selection and follow-up after PRLT. Hematological status, renal function and serum prostate specific antigen (PSA) levels were documented before and after therapy. Dosimetry was performed in 30 patients. 177Lu DOTAGA PSMA small molecule demonstrated very high tumor uptake, rapid blood clearance and fast renal washout resulting in high absorbed tumor doses (median, 3.3 mGy/MBq) as compared to normal organs. All patients tolerated the therapy without any acute adverse effects. Except mild reversible xerostomia in two patients, no long-term side effect was observed. No relevant hematotoxicity or renal impairment occurred. Decrease in PSA was noted in 45/56 (80%) and pain significantly reduced in 33% of patients. In 25 patients, followed up at least 6 months after ≥2 PSMA-RLT cycles, molecular response evaluation (68Ga-PSMA PET/CT) revealed partial remission (PR) in 14, stable disease (SD) in 2 and progressive disease (PD) in 9 patients. Contrast-enhanced CT exhibited PR in 5, SD in 13, and PD in 7 patients. The median progression-free survival was 13.7 months, and the median overall survival was not reached at follow-up of 28 months.
177Lu-PSMA-617
Between April 2013 and June 2018, intention-to-treat analysis was performed in 274 patients (mean age 71 years, mean Gleason score 8) with mCRPC. They received 1 to 11 PRLT cycles (total 824 courses) using 3.5 - 11.7 GBq (mean 6.7 GBq) of Lu-177 labeled PSMA ligand. Previous treatments included surgery, external beam radiation, chemotherapy , androgen deprivation and Ra-223 chloride. The most frequent sites of metastases were bone (n=228 patients), lymph node (209), liver (34) and lungs (36). Ga-68 PSMA PET/CT was used for initial evaluation and therapy response assessment (THERANOSTICS concept). Laboratory parameters included complete blood count, renal and liver function, electrolytes etc. PSA levels were documented before and regularly after therapy.
Any PSA decline was observed in 72 % of all patients, the best response was biochemical complete remission (PSA=0.0 ng/ml). Decrease in PSA by >50% was seen in 53% of cases. Median progression-free survival (according to RECIST 1.1) was 9.8 months. Median overall survival (at 61 months follow-up) was 30.9 months (96 patients deceased). G3-4 hematolo-gical toxicity was observed in <5% of patients and was more frequently associated with previous chemotherapy or Ra-223 treatment. Nephrotoxicity was not observed in any of the 274 patients treated, even if there was only a single functioning kidney present (n=17).
Pain reduced dramatically and the quality of life improved significantly in symptomatic patients (EORTC questionnaire).
In general, the patients tolerated the treatment very well with no severe acute or long-term side effects (observation period 64 months). The most common adverse effect was mild fatigue lasting for a few days after therapy. Radiation effect on salivary gland function was assessed using dynamic salivary gland scintigraphy before and after PRLT. Using a standardized questionnaire, <5% of patients reported mild dryness of mouth, which was mostly reversible.
First line (de novo) Lu-177 PSMA radioligand therapy was effective in 11 non-castrate metastatic prostate cancer, offering a significant survival benefit. Patients demonstrating a PSA decline of more than 50% after at least two PRLT cycles, lived significantly longer.
Additional treatment with newer antiandrogen agents (Abiraterone or Enzalutamide) in combination with 177Lu PRLT also prolonged survival.
Targeted Alpha radioligand therapy (ART)
The feasibility, toxicity and efficacy of targeted alpha radioligand therapy (ART) in end-stage, metastatic, treatment-resistant prostate cancer, having progressed under Lu-177 PSMA radioligand therapy, were evaluated in a pilot study in 10 patients with Bismuth-213 PSMA-617 (1-2 cycles, 2-4 applications per cycle). Bi-213 (t1/2 46 minutes) was obtained from an Ac-225/ Bi-213 generator (provided by Isotope Technologies Garching (ITM), Munich Germany). The median administered activity of Bi-213 PSMA per cycle was 390 MBq (155 – 623 MBq). All patients tolerated the therapy very well without any acute adverse effects. Decrease in PSA was noted in 43 % of patients. With the administered radioactivities mentioned, no significant acute / subacute toxicity was noted and minor responses could be demonstrated.
Since February 2018, 22 patients have been treated with Actinium-225 PSMA-617 or with a combination of Lu-177 / Ac-225 PSMA (TANDEM-ART). The results are extremely promising and will be presented in more detail.
Conclusions
PSMA Radioligand Therapy with 177Lu-PSMA has been performed since April 2013 in 274 patients (total number of 824 administered treatment cycles). PRLT of mCRPC is feasible, safe (especially no nephrotoxicity as noted without renal protection) and effective with appropriate selection and follow-up of patients by 68Ga-PSMA PET/CT applying the concept of Theranostics (Baum et al. 2015, Kulkarni et al. 2016).
Targeted alpha radioligand therapy using Ac-225 PSMA or TANDEM-ART appears to be extremely promising for Precision Oncology of end-stage metastatic treatment-resistant prostate cancer, progressing after castration, newer hormonal agents, chemotherapy as well as after progression under Lu-177 PRLT.
Randomized clinical trials have now started to confirm the results of this extremely promising new concept of molecular targeted radiotherapy.
Title: Theranostic approach: The present and the future
Biography:
Charl Rafael Macedo da Silva received the MD, PhD in Medicine from OPORTO Medical University. Director of the Nuclear Medicine Department, Health Service of the Autonomous Region of Madeira, E.P.E. (SESARAM, E.P.E.), Madeira, Portugal, Responsible for the construction and licensing of the Nuclear Medicine Unit of SESARAM, EPE, between January 2, 20 and April 4, 205 - Installation financed by the Genhymape Project belonging to the Research Nucleus of Cardiology of SESARAM, EPE, financed 85% the EU. He is the Directorate General of Health, Ministry of Health, Portugal; *Coordinator of Public Unit of Nuclear Medicine - SESARAM, E.PE. - Funchal, Portugal. He has presented 80+ oral and poster presentations in International, National and Regional Nuclear Medicine Meetings.
Abstract:
Theranostic approach: The present and the future
R Macedo, C Rodrigues, F Drumond, M Ferreira and F Rodrigues
Health Public Service, Portugal
Personalized medicine is having an increasingly wide-ranging discussion today. For this, nuclear medicine has played its fundamental role in the diagnosis and decision in the treatment of diverse oncological pathologies, in a perspective increasingly focused on the individual. Taking into account that we are witnessing an increase in cancer prevalence on a global scale, we must also focus on an economistic view, both due to the costs involved in all procedures currently underway for the entire follow-up process, without prejudice to the quality of the diagnosis / treatment. Thus, the purpose of this presentation is based on the description of the means of diagnosis and therapy currently performed by the personalized nuclear / molecular medicine and on the signaling of possible pathways to follow, with the most current diagnostic means such as pet / MRI, as form of diagnostic evaluation and assessment of response to therapy, integrated. What if we could move to the investment of new positron-emitting radiopharmaceuticals with paramagnetic properties ideal for MRI imaging? Simultaneous acquisition may provide new perspectives for imaging diagnosis, a possible better evaluation of response to therapy with cost reduction and less exposure to ionizing radiation. This presentation aims to promote the discussion about the development of this possibility of functional / molecular and structural / macroscopic assessment of oncological cases in an integrated and personalized perspective. What is the current state of the art about these possible new radiopharmaceuticals and what is the perspective of their use in the short and medium term?
Oral Session 1:
- Nuclear Medicine: Current Research, Innovation and Application | Neurology: Brain and CNS research | Molecular Imaging, Functional Imaging and Integrated Therapy
Chair
Rafael Macedo
Health Public Service, Madeira, Portugal
Co-Chair
Hashim Ahmed
SudRad Consulting, UK
Title: The role of deep learning in future of nuclear medicine and molecular imaging
Biography:
Hashim Ahmed is a Medical Physicist and the Co-founder of SudRad Consulting Ltd, UK. In the past, he has worked as a Medical Physicist at Hammersmith Hospital, London Mount Vernon Hospital, St Thomas & Guy’s Hospital at UK. He is a member of the Institute of Physics, Graduate Member of Institute of Physics and Engineering in Medicine, Former secretary of Sudanese Medical Physicist Association (SMPA). His research interests are in are in multimodality imaging, image quantification, image registration, quality control and dosimetry as well machine learning in medical imaging.
Abstract:
Recent developments in deep learning machine, a subfield of artificial intelligence, which is based on experience and learning, has shown promising perspective and potential due its accuracy and efficiency in addressing challenges faced in real life. It exploits the available big data in other sectors as well as nuclear medicine and molecular imaging with a valuable and robust outcome. Despite significant advances following the introduction of deep learning in radiology and drug delivery, nuclear medicine has been slow in adapting the revolutionary technology. This has affected the possibility of improving dose reduction, automated image analysis and quantification, dosimetry and integrating other clinical data to enhance personalized and precise medicine and image reporting. Emerging technologies have provided nuclear medicine with immense clinical data that remains under-utilized. Introducing deep learning into nuclear medicine, molecular imaging and dosimetry can improve clinical outcomes; which allow for cost effective care services and better patient quality of life. This paper aims to highlight the significant role that the learning machine could play in improving the quality of nuclear medicine and molecular imaging services and it addresses the challenges facing nuclear medicine and the expanding molecular imaging field. It also reviews the current state of art of deep learning and its applications in nuclear medicine and molecular imaging. In addition the article highlights the importance of the future role of this technology in enhancing clinical knowledge and decision making. Finally, the issues of data ownership and security will be discussed.
Title: Imaging the dopaminergic system: Analyzing the pre and postsynaptic pathways and its clinical relevance in Parkinson’s disease
Biography:
Belén Rivera Bravo has completed the General Medicine Degree in 2004 at the Faculty of Medicine of the National Autonomous University of Mexico (UNAM). She is working as Nuclear Medicine Specialist (2007), and as a Fellow in Oncologic Nuclear Medicine (2008), both in UNAM. She is the Head of the PET/CT Unit of the Faculty of Medicine (FM) of UNAM. She is currently appointed as the Professor of the Faculty of Medicine of UNAM since 2015 and is the Head of research projects in molecular imaging, with indexed publications related to Nuclear Medicine and Molecular Imaging.
Abstract:
The aim of this study is to introduce the radiopharmaceuticals for imaging the dopaminergic system at pre and postsynaptic levels: 18F-FDOPA, 11C-DTBZ and 11C-Raclopride, describing its mechanism of uptake and biodistribution of each one. The utility of these radiopharmaceuticals involved in the PET/CT study of the patient with Parkinson´s Disease (PD) for the differential diagnosis of PD versus Parkinsonian syndromes (progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration). These images have clinical relevance as they image the dopaminergic system at pre and postsynaptic pathways, reflecting the molecular alteration site of dopamine metabolism. It is especially useful for differential diagnosis of patients diagnosed and treated as Parkinson´s disease, but not responding to levodopa medication. At our center we are realizing quantitative analysis of the images with parametric analysis, heterogeneity characterization of the alterations and determining the receptor binding potential of the radiopharmaceuticals.
Conclusion: Imaging of the alterations of the dopaminergic pathway at molecular level provides relevant information for clinical decision making in PD patients. Quantitative imaging analysis may provide more specific and precise data of metabolic alterations regarding the severity of the disease and treatment response that may establish newer parameters for understanding PD, resulting in personalized and precise medicine.
Title: PET/CT in gynaecological cancer with special focus on cervical cancer
Biography:
Paulina Cegla has graduated from the University of Medical Science in 2013 with Master of Electroradiology degree. Currently she is pursuing PhD at the same University. Since 2011 she works as a Nuclear Medicine Radiographer at Department of Nuclear Medicine in Greater Poland Cancer Centre. She presented over 20 scientific works in European and world conferences of nuclear medicine and several articles in reputed journals.
Abstract:
Gynaecological cancers are staging by FIGO classification however more often nuclear medicine techniques are used to complete FIGO stage and determine the appropriate stage of disease. Nuclear medicine techniques has advantages over conventional imaging methods cause they gives us information not only about anatomical changes taking place in the body, but more important about functional changes which usually occurs earlier than anatomical changes. The most common radiotracer 18F-FDG is used in gynaecological malignancy for diagnosis, staging and treatment planning in endometrial cancer, ovarian cancer and cervical cancer. PET/CT provides whole-body imaging including primary tumor, lymph nodes and distant metastasis.The assessment of metabolic activity and the extent of the tumor mass has an increasing importance for radiotherapy planning. In cervical cancer FDG-PET/CT has a special application. Based on our preliminary results in over 30% PET/CT examination changed radically the treatment method. Recently, more and more interest has been generated focused on more specific radiotracers that do not accumulate in the inflammatory process and might be helpful in radiotherapy planning like the thymidine analog - 3’-deoxy-3’-[18F]fluorothymidine (FLT). The aim of this presentation is to discuss the potential role of PET/CT with different radiotracer in gynaecological malignancy with special focus of cervical cancer.
Title: L-Carnitine: A hepatoprotective agent against radioiodine toxicity in rats
Biography:
Aziz Mutlu Barlas has graduated from Gazi University Medical Faculty in Ankara/Turkey in 1997. He started General Surgery education at University of Health Sciences, Ankara Training and Research Hospital. He is still working as General Surgery specialist at the same hospital. He has published more than 20 papers in reputed journals.
Abstract:
Objective: Radioactive iodine (RAI), which has much hematological and non-hematological toxicity, is a well-known and widely-used radionuclide for the treatment of metastases in differentiated thyroid carcinomas. Cell death caused by the ionizing radiation is related to free radical formation. L-carnitine is an essential nutrient that the body uses to convert fat into energy. L-carnitine has effective free radical scavenging, superoxide anion radical scavenging, and hydrogen peroxide scavenging activities. In the present study, the hepatoprotective effect of L-Carnitine against RAI toxicity was evaluated.
Materials and methods: Thirty-six rats were randomly divided into three groups as untreated control (Group 1); oral radioiodine administrated rats (Group 2), and Group 3 (oral RAI and daily intraperitoneal injection of 200 mg/rat L-carnitine). In the third group, L-carnitine administration was started 2 days before and continued for five days after RAI administration. Twenty-four hours after the administration of the last dose of L-carnitine, liver samples were taken for biochemical and histopathological evaluation.
Results: The histopathological damage in the L-carnitine group was significantly less than the RAI group (p<0.05 for all pathological parameters). The levels of the tissue malondialdehyde and fluorescent oxidation products levels were lower, and the total sulphydryl levels were higher in L-carnitine group when compared with RAI group. The differences were statistically significant between these groups for all parameters (p<0.05).
Conclusion: L-carnitine administration significantly decreased RAI-induced histopathological damage, which might be due to its antioxidant effects.
Title: Is VCUG really necessary for children older than two years with recurrent urinary tract infection?
Biography:
Fikri Selcuk Simsek is currently working at the Nuclear Medicine department of Firat University Medical Faculty, Turkey. He has many publications in reputed international journals and is an eminent researcher, representing his institution in many international conferences as well.
fselcuksimsek@gmail.com
Abstract:
Purpose: VUR incidence is around 1.0% in general population, but it occurs as high as 25.0-50.0% among children with UTI. Presence of VUR and UTI together is considered a very important risk factor in development of renal scar. After the first UTI urinary system imaging generally not recommended. If patients are of age between 2-24 months with recurrent UTI, guidelines suggests VCUG. For children >24 months with recurrent UTI, a large number of clinical and biochemical parameters evaluated for VCUG. However this modality could cause high gonadal radiation exposure, increased infection risk, in addition to higher costs and increased morbidity. Our aim is to investigate, is there any chance to discriminate High Grade VUR from others via 99mTc-DMSA scintigraphy in children >24 months with recurrent UTI.
Material-Methods: Patients whom >24 months, underwent 99mTc-DMSA scintigraphy and VCUG for recurrent UTI between 2010 and 2016 were retrospectively evaluated in our database. Among them, if patients have normal scintigraphy, they included in the study. We calculated the possibility of high grade VUR in scintigraphy negative patients. VCUG accepted as gold standart for grading VUR.
Findings: There wasn’t any high grade VUR in 42/44 kidney and 20/22 patients with scintigraphy negative patients. Both children with reflux were female with six and nine years old. Both refluxes were Grade 4 and 99mTc-DMSA scintigraphy had 95.5% NPV for high grade VUR.
Conclusion: Tc-99mTc-DMSA scintigraphy in >24 months children with recurrent UTI has high NPV for High Grade VUR. When it is remembered that, Grade 4 VUR can be removed with appropriate treatment and follow-up without surgery, 99mTc-DMSA scintigraphy is an logical alternative for this group of patients. Thus, much lower gonadal radiation exposure, decreased infection risk, much lower costs for medicare system and decreased morbidity can be achieved.
Title: Molecular imaging in prostate cancer: Theranostics approach
Biography:
Fahad Marafi is a consultant Nuclear Medicine Physician and is the Director of Jaber Al-Ahmad Molecular Imaging Center, Kuwait as well as President of Kuwait Society of Nuclear Medicine and Molecular Imaging. His main Interests are in PET/CT non-FDG Imaging and Radionuclide Therapy.
Abstract:
The lecture goes through a journey from basics of diagnostics imaging to new advances in Molecular Imaging and radionuclide therapy. The approach focuses on functional imaging and how it is utilized to come up with a new era in medical practice called Theranostics “Therapy and Diagnosis”.
Title: Utility of bone scan quantitative parameters for the evaluation of prostate cancer patients
Biography:
Nayab Mustansar is currently working as Nuclear Physician Consultant in CENAR Quetta. She did her specialization in Nuclear Medicine from PIEAS University Islamabad in 2014. She had served in different well recognized institute of national importance including "NORI Islamabad, Shaukat Khanum Research Cebttre Lahore, Nuclear Medicine Centre Rawalpindi and INOR Lahore.
She has made publications in the Journal of Oncology. Her research areas are bone scans, physiology and quantification of metastasis via bone scans.
dr.m.nayab@gmail.com
Abstract:
Prostate Cancer is one of the common cancers in the world. It could primarily disseminate to the bone and can lead to death. In order to address its life threatening distant metastasis it is important to diagnose it earlier for timely treatment. Bone metastasis is usually diagnosed deploying bone scan imaging. However interpretation of the bone scans is a tedious procedure for the physicians and often leads to misinterpretation either as overestimation or underestimation of the metastasis. To minimize the risk of misinterpretation, one of the accurate methods is quantitative analysis of the bone scans in order to ascertain, whether a metastatic lesion is present or not. There are several methods to-date which can be used to analyze the extent of such lesions. (For example, quantitation of the bone scan using quantitation methods i-e % BSI (Bone scan index), % PAB (Positive area on bone scans), EOD (extent of disease) and BLS (Bone lesion scoring)). These methods are used for prognostication of survival and response to treatment on serial scans. The extent of fidelity of these all available quantitatation methods is not clear when used altogether in a single baseline bone scan. Therefore, the aim of this study is to use all available bone scan quantitative parameters on a baseline bone scans and to compare them all. Moreover, an improved methodology is introduced by comparing the results with the individual methods reported in literature and with PSA levels.
141 patients with histopathologically proved prostate cancer were chosen to implement all the four quantitative parameters on individual baseline bone scans. After which, for the calculation of risk of progression or regression of disease and survival rate, 40 patients were chosen from the same dataset. A serial follow up scan was performed to calculate 2-years survival rate.
Keynote Session:
Title: 177Lu-PSMA-617 radioligand therapy for lymph node metastatic prostate cancer
Biography:
Finn Edler von Eyben is specialist in internal medicine and oncology. He defended a thesis in Sweden 1983 and in Denmark 2005 He has worked as chief consultant for a department of Internal Medicine in Nuuk, Greenland, and as consultant in oncology at department of oncology, Tawam hospital, Abu Dhabi, the United Arab Emirates. He has published 145 research articles, and also published two books. According to Researchgate, he has had 2950 reads and 1641 citations of his publications.
Abstract:
177Lu-PSMA-617 radioligand therapy for lymph node metastatic prostate cancer
Finn Edler von Eyben
Center of Tobacco Control Research, Denmark
Patients with lymph node metastases of prostate cancer (LNM) appear to respond better to 177Lu-prostate specific membrane antigen (PSMA)-617 radioligand therapy (RLT) than patients with end-stage prostate cancer. The present study aimed to analyze the outcome with 177Lu-PSMA-617 RLT for a group of patients with LNM. In this multicenter study, we evaluated the antitumor effect and the safety of using 177Lu-PSMA-617 RLT for 36 patients with LNM and 10 patients with LNM together with one or two bone metastases. Cumulative 177Lu activity of 177Lu-PSMA-617 RLT was median 14∙8 GBq (IQR 12∙0-20∙4). The largest lowering of PSA was median 86% (IQR 68-99). The patients did not develop grade 3-4 myelosuppression. During follow-up, 25 (54%) patients had PSA progression. 23 (50%) patients developed new metastases and one (2%) patient died of prostate cancer during follow-up. Patients with LNM and PSA before treatment <4 µg/L had a lower PSA after treatment with 177Lu-PSMA-617 RLT than patients with PSA before the treatment >4 µg/L (p=0∙001). Patients with Gleason score ≤8 had a better PSA progression-free survival than patients with Gleason score 9 (p=0∙027). Patients with LNM had a better PSA progression-free survival than patients with LNM combined with one and two bone metastases (p=0∙0003). In conclusion, the outcome with 177Lu-PSMA-617 RLT for patients with recurrent LNM was markedly better for patients with Gleason score ≤8 and with LNM than for patients with Gleason score 9 and with LNM combined with one or two bone metastases.
Title: Female-to-male differences in CAD, imaging microvascular dysfunction with 13N-Ammonia PET/CT
Biography:
Fred Verzijlbergen is Professor and the Head of the Department of Nuclear Medicine at Radboud Medical Centre, Netherlands. He has made over 140 publications in reputed journals. He is Advisor of the Board of EANM (European Association of Nuclear Medicine) and also a past president (2013-2014) for the EANM.
Abstract:
Female-to-Male differences in CAD, imaging microvascular dysfunction with
13N-Ammonia PET/CT
Fred Verzijlbergen
Radboud University Medical Centre, The Netherlands
Evidence gained during the last decades indicates that the full spectrum of CAD in women extends beyond atherosclerotic stenoses in the epicardial coronary arteries and may include dysfunction of the coronary microvasculature and endothelium. These concepts create a diagnostic challenge since the coronary microvasculature cannot be imaged. Additional investigations beyond standard stress tests are necessary to define the etiology of symptoms in women. This is relevant since it has been demonstrated that microvascular dysfunction in the smaller coronary arterioles may cause chronic ischemia, acute myocardial infarction and stress-induced cardiomyopathy. The 2014 American Heart Association Consensus Statement on non-invasive diagnostic testing in women with suspected Ischemic Heart Disease highlighted the development of novel diagnostic tools that have an expanded role in the evaluation of symptomatic female patients to detect not only epicardial coronary stenosis, but also identification of ischemia resulting from microvascular dysfunction. In this presentation we will give an overview of recent functional and physiologic assessments of endothelial and microvascular function and demonstrate the results of 13N-ammonia PET/CT studies in 32 patients without significant epicardial CAD who were suspected of micro vascular coronary dysfunction.
Oral Session 1:
- Radionuclide Therapy | Radiobiology and Radiochemistry | Radiation Dosimetry | Endocrine Theranostics
Chair
Finn Edler von Eyben
Center for Tobacco Control Research, Denmark
Co-Chair
Fred Verzijlbergen
Radboud University Medical Centre, Netherlands
Title: Radiobiology of targeted radionuclide therapy to improve treatment effects
Biography:
Julie Nonnekens completed her PhD in molecular oncology at the University of Toulouse, France in 2013. She pursued Postdoctoral studies at the Hubrecht Institute and Erasmus MC in the Netherlands and is now an assistant professor at the Erasmus MC. Her research focusses on the radiobiology of targeted radionuclide therapy and is published in high-ranking journals. Furthermore, Julie was awarded two young investigator awards and obtained various grants to continue her research.
j.nonnekens@erasmusmc.nl
Abstract:
Radiobiological principles of external beam- and brachy radiotherapy have been studied for decades, while the radiobiology of radionuclide therapy is still in its infancy. During peptide receptor radionuclide therapy (PRRT) of metastasized neuroendocrine tumors (NETs) with overexpression of somatostatin receptors (SSTR2), Lutetium-177 is targeted to the tumor via coupling to the somatostatin analogue DOTA-[Tyr3]octreotate (177Lu-DOTA-TATE), that has high affinity to SSTR2. Lutetium-177’s β-particles (mean energy 0.133MeV) will induce DNA damage leading to tumor cell death with limited harm to healthy tissues. Patient treatment strongly increases progression-free survival and life quality. There is nevertheless still room for improvement, as very few patients are cured at this stage of disease. For possible future therapy optimizations, it is essential to have a better understanding of local treatment effects, both in tumor and healthy tissues. To gain insight in the underlying radiobiological principles, we characterized the PRRT-induced DNA damage response (DDR) in cell lines, ex vivo cultured human NET slices and xenografted mice. PRRT induces DNA double strand break (DSBs) which are repaired over time. Our results show that DDR inhibitors (PARPi, DNA-PKi and ATMi) differentially impair DNA repair (radiosensitizers) and vastly increase cell death in SSTR2-positive cells and NET slices, while SSTR-negative cells are not sensitized to PRRT. Furthermore, xenografted mice were followed for 14 days post PRRT and scanned with SPECT/MRI. Dosimetric calculations were performed based on both in vivo imaging and ex vivo biodistribution data. Our analyses show that PRRT produced DSBs in the tumor and dose limiting organs; the kidneys and bone marrow. DSBs in the tumor (dose 10.5Gy over 14days) were observed until at least 14days post treatment (also massive apoptosis induction), while DSBs in the bone marrow and kidneys (dose 3.7Gy over 14days) were only observed transiently until 2 days after treatment, illustrating the window of opportunity for combination therapy with DDR inhibitors.
Title: The efficacy of leukotriene receptor antagonist on radioiodine-induced lung fibrosis
Biography:
Aylin Akbulut has completed her fellowship on Nuclear Medicine at the age of 30 years from Gazi University and she had postdoctoral studies at Geneva University, Switzerland with Prof O. Ratib. Prof Korkmaz, M.D., PhD is the founding director of Nuclear Medicine Department in University of Health Sciences, Ankara Training and Research Hospital. After her fellowship on Nuclear Medicine, she had her postdoctoral studies on radio-peptides at University of Texas MD Anderson Cancer Center, USA. She has published more than 50 papers in reputed journals and has been serving as an editorial board member of repute.
aylin0257@yahoo.com
Abstract:
Objective: Radioiodine therapy (RAI) is a standard treatment for the treatment of metastases after total thyroidectomy in differentiated thyroid carcinomas. However, the side effects of RAI are well known. Montelukast is an antagonist of the leukotriene receptor that inhibits the binding of cysteinyl leukotrienes to the CysLT1 receptor. Anti-fibrotic effect of montelukastin in induced lung fibrosis with bleomycin was evaluated. We examined the immunohistopathological effect of montelukast on in rat lungs after RAI.
Materials and methods: 30 Wistar albino rats were randomly divided into 3 groups each containing 10 rats. In Group 1 (control group) only total thyroidectomy was performed; Group 2 had RAI after total thyroidectomy; and Group 3 had total thyroidectomy and montelukast before and after RAI treatment. All rats were sacrified after 12 weeks. By immunohistochemical (IHC) methods TNF-Alpha and TGF-beta tissue expression were evaluated to determine the degree of fibrosis in the lungs.
Results: TNF-Alpha and TGF-beta tissue expression in Group 2 was significantly higher than Group 1 (p<0.01). However, no significant difference was found between Group 3 and group 1 in terms of TNF-alpha and TGF-beta tissue expression (p>0.01). TNF-alpha and TGF-beta tissue expression was significantly less observed in Group 3 compared to Group 2 (p<0.05).
Conclusion: Co-administration of montelukast significantly prevented RAI-induced immunohistopathological alterations, which can be associated with the radioprotective effects of montelukast.
Title: Aylin Akbulut
Biography:
Aylin Akbulut has completed her fellowship on Nuclear Medicine at the age of 30 years from Gazi University and she had postdoctoral studies at Geneva University, Switzerland with Prof O Ratib, Prof Korkmaz, MD, PhD is the founding director of Nuclear Medicine Department in University of Health Sciences, Ankara Training and Research Hospital. After her fellowship on Nuclear Medicine, she had her Postdoctoral studies on radio-peptides at University of Texas MD Anderson Cancer Center, USA. She has published more than 50 papers in reputed journals and has been serving as an editorial board member of repute.
aylin0257@yahoo.com
Abstract:
Objective: Radioactive iodine-131 (RAI) related damage is well recognised in several tissues including liver. Coenzyme Q10, is a distinguished anti-oxidant, and very recent studies have shown the hepatoprotective effect of coenzyme Q10 in different hepatotoxicities. Our aim was to evaluate the radioprotective effects of coenzyme Q10 in RAI-induced liver toxicity, which has not been evaluated in English literature yet.
Materials and methods: Thirty-six rats were divided into three groups. Group 1 was the control group, Group 2 was administered 111 MBq/kg of RAI and Group 3 was administered coenzyme Q10 together with RAI. After the administration of the last dose of coenzyme Q10, the animals were decapitated and liver tissue samples were evaluated by histopathology and for oxidative stress parameters.
Results: Group 2 rats showed significantly elevated values of malondialdehyde (MDA) and fluorescent oxidation products (FOP) in liver tissues; however, the total sulphydryl (total-SH) level was decreased compared to Group 1 and Group 3. In addition, the histopathological damage scores in Group 2 were significantly higher compared to other groups (p<0.05 for all histopathological parameters). The total tissue MDA, and FOP levels of Group 3 were lower than Group 2 (p < 0.05) and total-SH level was higher than Group 2 (p < 0.05). Liver MDA and FOP levels of Group 3 were higher than Group 1. However, the difference was not statistically significant (p > 0.05). The histopathological damage in Group 3 was significantly less than the damage in Group 2 (p<0.05 for all pathological parameters). Conclusion: We conclude that depletion of total-SH levels, and increased levels of PFOP and liver MDA are the results of RAI-induced liver damage concordant with histopathology. Moreover, the radioprotective effect of coenzyme Q10 on the liver after RAI therapy was presented in this study and antioxidant activities are likely to be involved in the mechanism underlying the radioprotective effects of coenzyme Q10.
Title: Imaging in the dopaminergic pathway using three different positron emission tomography radiotracers in Parkinson’s disease
Biography:
Abstract:
Introduction: It is well known that the dopaminergic system plays an important role in neurodegenerative disorders such as Parkinson's, Alzheimer's and Huntington's diseases. Nowadays, technological advances in molecular imaging have made it possible to obtain, in vivo and non-invasively, information on alterations in dopamine synthesis, integrity of dopaminergic terminals and receptor densities, invaluable information to understand the mechanisms underlying pathogenesis and efficacy of treatments for these diseases Positron emission tomography (PET) provides these characteristics, provided that adequate tracers are available to investigate presynaptic and postsynaptic function. The objective of this research is to evaluate the utility of the combined use of presynaptic and post-synaptic PET radiopharmaceuticals to evaluate Parkinson's disease (PD) and correlate the analysis of the simple uptake rate in striatal subregions (SSR) with the unified qualification scale of Parkinson's disease (mUPDRS
Methods: The radiopharmaceuticals evaluated were 6- [18F] Fluoro-L-DOPA (FDOPA), [11C] Raclopride (RAC) and (+) - alpha- [11C] Dihydrotetrabenazine (DTBZ). We included eight patients diagnosed with PD (2f, 6m, 43-74y, mean 56y) and 4 healthy voluntary male controls (30-72y, mean 53.8y). All patients underwent DTBZ-PET scans and an additional study with FDOPA or RAC, at least a week apart. The controls were studied with a single tracer. The scans were acquired in a Siemens Biograph 64 PET / CT after the intravenous administration of radiopharmaceuticals (185-370 MBq). Brain emission scans of 30 minutes 20 minutes after the DTBZ and RAC injection were obtained, while scans of 15 minutes were acquired after 75 minutes after the injection for FDOPA. All subjects studied with FDOPA received 150 mg of carbidopa to block peripheral decarboxylation. The images were reconstructed using an OSEM-2D algorithm and analyzed with OsiriX v. 6.0 of 32 bits. The regions of interest (0.5 cm2) were drawn in caudate, putamen (anterior, medial and posterior), and the occipital cortex was used as a reference region. Striatal to occipital relationships (SOR) were obtained for each Ssr and correlated with the mUPDRS score. Statistical analysis (Pearson correlation, α = 0.05) was performed with GraphPad Prism 5.
Results: The typical images of PET for controls and patients with PD with each radiopharmaceutical are shown in Fig. 1 and Fig. 2. FDOPA measures the synthesis of dopamine through the expression of DDC, DTBZ is a marker of activity of VMAT2 and RAC evaluates the density of D2 receptors. Note the coincidence between the images with DTBZ and FDOPA (reduced uptake in the putamen) and the corresponding lack of coincidence with the RAC images (increased absorption in the putamen) in patients with PD.
Conclusions: To our knowledge, this is the first report that uses 3 different radiopharmaceuticals in a single study in humans. The trackers studied in this investigation showed all the tools for evaluating PD and the information obtained with each radiopharmaceutical is complementary as a key final measure of the efficacy of clinical treatments. The correlations between the mUPDRS score and the SOR values for the different Ssr for DTBZ were all statistically significant (α = 0.05), specifically for the putamen subregions, suggesting that this method could be useful for staging, following the evolution and compare intrasubjects and, in addition, intersubjects in the evaluation of PD. Given that FDOPA and DTBZ show similar information, a combination of RAC-DTBZ or RAC-FDOPA could be the best option if it is necessary to choose two radiopharmaceuticals.
Title: Doses during lymphoscintigraphy in gyneacological cancer - Sentinel lymph node localization procedure
Biography:
Patrycja Mantaj has graduated from the University Adam Mickiewicz University in Poznan in 2006 with Master of Medical Physics. In 2010, she earned IOR certificate. Since 2006 she works as Radiation Protection Officer in Greater Poland Cancer Centre.
patrycja.mantaj@wp.pl
Abstract:
Lymphoscintigraphy is a method of imaging the lymphatic pathways and the lymph nodes using radiopharmaceuticals (AlbuminColloid-Tc99m) that are absorbed and transported in the lymphatic system. This method is widely used in the localization of sentinel lymph node in various diseases; mainly breast cancer nut also plays an important role in gyneacological cancers. Lymphoscintigraphy is also a part of a multidisciplinary procedure of the localization and examination of the sentinel lymph node that involve multiple professionals including nuclear medicine staff, nurses, surgeons, operating room staff and the pathologists. Aim of this study was to compare the doses between NMT, Surgeons and other doctors included in lymphoscintigraphy in gyneacological cancer. The highest exposure is noted in the nuclear medicine technologist preparing the radiopharmaceuticals and the nuclear medicine specialist/nurse/surgeon injecting the tracer. Radiation exposure to the surgeon in the operating room, other operating room personnel and pathologists is much smaller and with the exception of a ‘one-day-procedure’ this method can be safely used without special restrictions.
Title: Performance of neutron detector 6LiF+ZnS(Ag)
Biography:
Abderrahim El Yazzaoui is a PhD student in Medical Physics under the guidance of Professor Amina Kharchaf at the Faculty of Sciences Kenitra, University Ibn Tofail, Morocco. He holds a master's degree in Nuclear Techniques and Radiation Protection. In his research, he is interested in protecting patients and workers against ionizing radiation; he has completed internship in the National Centre for Nuclear Energy, Sciences and Technology Techniques, and research laboratories.
abderrahimphy@gmail.com
Abstract:
This work presents a study on technological advances in nuclear instrumentation, specifically neutron detection and counting, for applications in radiation protection and nuclear security risk prevention. Currently the majority of security monitoring systems use proportional counters filled with 3He helium gas to detect neutron sources. Due to the severe global shortage of 3He, a replacement technology for neutron detection is needed in the near future. Several alternative replacement detectors are available now, among these detectors is the 6LiF+ZnS (Ag) scintillation neutron detector having a large cross section of neutron interaction. In this work we have shown that the 6LiF+ZnS(Ag) scintillator meet the following requirements: a very good sensitivity, excellent stability during counting time, and a quick response from the associated electronic module. These features are sufficient for it to be used in the detection of nuclear and radioactive materials nuclear material and radioactive material that may be used in a criminal or unauthorized act, to ensure nuclear security in the national and international territory.
Title: Clinical Translation and First In-Human Use of [44Sc] Sc-PSMA-617 for PET Imaging of Metastasized Castrate-Resistant Prostate Cancer
Biography:
Dr. Elisabeth Eppard is Radiochemist at the Department of Nuclear Medicine of the University Hospital Bonn. After obtaining her diploma in chemistry from the Johannes Gutenberg University Mainz in 2009, she started her Ph.D. at the Institute of Nuclear Chemistry at the group of Prof. Frank Roesch where she worked on radiometal based radiopharmaceuticals obtaining her Ph.D. in 2013. In 2014 she moved to the Department of Nuclear Medicine of the University Hospital Bonn. There Dr. Eppard continued to work with radiometal based radiopharmaceuticals for clinical application. As Junior Research Group Leader she is focusing on the application of scandium-44 for pre-therapeutic dosimetry in clinical routine.
elisabeth.eppard@ukbonn.de
Abstract:
PSMA-617 has proven high potential in PSMA radioligand therapy of prostate cancer as well as PET imaging. Considering the relatively short physical half-life of gallium-68 this positron emitter precludes prolonged acquisition periods, as required for e.g. for pre-therapeutic dosimetry. In this context, the positron emitter scandium-44 is an attractive alternative for PET imaging. We report the synthesis and in vitro characterization of [44Sc]Sc-PSMA-617 as radiopharmaceutical and clinical translation as part of a first in-human study.
PSMA-617 was labeled with scandium-44 obtained from a 44Ti/44Sc radionuclide generator and evaluated in vitro and in cell studies using PSMA+ LNCaP cells. A first-in-human investigation was subsequently carried out in a cohort of 4 patients registered for 177Lu-therapy. [44Sc]Sc-PSMA-617 were applied via intravenous injection (i.v.), respectively. A Siemens Biograph 2 PET/CT system was used to acquire initial dynamic PET data in list mode followed by static PET/CT data. Dynamic images were reconstructed as 6 data sets of 300 s each. SUV values in different organs and lesions were measured and compared to [68Ga]Ga-PSMA-11 data of the same patients. Residence times and organ absorbed doses were calculated using OLINDA/EXM software.
Quantitative radiochemical yields of ≥98 % were achieved with apparent molar activity of 6.69±0.78 MBq/nmol. [44Sc]Sc-PSMA-617 showed high stability (>95 %) in serum for 24 h. The binding affinity and internalization were determined in PSMA+ LNCaP cells and compared to [68Ga]Ga-PSMA-11. SUV values were significantly lower in the kidneys compared to [68Ga]Ga-PSMA-11. All other measured SUV values did not show a statistically significant difference. The tumor to liver ratios were higher than for [68Ga]Ga-PSMA-11 and no statistically significant differences were observed. Total and % activity were highest in liver followed by kidneys, spleen, small intestine and salivary glands. Kidneys received the highest radiation absorbed dose.
In conclusion [44Sc]Sc-PSMA-617 is suitable for PET imaging of prostate cancer tissue enabling pre-therapeutic dosimetry in clinical settings.
Oral Session 2:
- Workshop
Title: A practical workshop about four software applications of nuclear medicine and radiopharmacy
Biography:
Jesus Luis Gomez Perales has completed degree in Chemistry at the University of Murcia, Spain in 1992.
He also accomplished radiopharmacy speciality at “Son Dureta” University Hospital, Palma de Mallorca, Spain in 1997. And he received PhD from the Faculty of Medicine of Cádiz, Spain in 2006. He is the Head of Radiopharmacy in the Nuclear Medicine Service of "Puerta del Mar" University Hospital, Cádiz, Spain since 1998. He has published 11 papers in reputed journals and more than 40 communications to national and international congresses.
jesusl.gomez.sspa@juntadeandalucia.es
Abstract:
This workshop will explain how to use four software applications on nuclear medicine and radiopharmacy. Nucleolab is a shareware application for performing calculations of nuclear medicine and radiopharmacy. Radiolab is a shareware designed for comprehensive management of hospital radiopharmacies and institutes that prepare radiopharmaceuticals within their own facilities only for in-house use. Dosisrad is a freeware program for automatic calculation of the radiation dosimetry of radiopharmaceuticals administered to patients. Datinrad is a freeware database with information on interactions of drugs with radiopharmaceuticals and adverse effects of radiopharmaceuticals.
