Current Radiopharmaceuticals - Volume 10, Issue 3, 2017

Background and Objective: The use of amiodarone for the treatment of ventricular and supraventricular dysrhythmias brings in organism an increased amount of iodine, interfering with thyroid function. If the treatment needs to be interrupted, iodine remains at abnormal levels for months or even years. The aim of the study was to review the literature regarding the optimal tests for early diagnostic and to analyze the role of nuclear medicine tests in the differential and correct assessment of the amiodarone-induced thyroid pathology. Methods: We made a review of available publications in PUBMED referring the amiodaroneinduced thyroid pathology, focusing on the differential diagnosis, made by nuclear medicine tests, of hypothyroidism (AIH) and hyperthyroidism expressed as: type I amiodarone induced thyrotoxicosis (AIT I), type II amiodarone induced thyrotoxicosis (AIT II), and less frequently as a mixt form, type III amiodarone induced thyrotoxicosis (AIT III). We presented cases from the database of a tertiary center in Cluj-Napoca, Romania. Results: Despite the frequent complication of thyroid function, this pathology is underestimated and diagnosed. There is a limited number of studies and clear protocols, especially in the mixed forms cases. This increase in iodine uptake interferes seriously with thyroid hormone production and release. The nuclear medicine tests are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The destruction of the follicular cells can result in the release of excessive thyroid hormone into the circulation, with potential development of atrial fibrillation, worsening the cardiac disease, so any benefic therapeutic procedure should be known; the use of radioiodine as therapy alternative, despite the known limitations induced by blockade was clear benefic in the case presented. A special attention needs to be addressed to those patients with differentiated thyroid cancer, which will be submitted to radioiodine therapy and are under chronic therapy with amiodarone. Conclusion: The nuclear medicine procedures are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The radioiodine is not recommended in AIT, due to stunning effect induced by iodine excess, but in some special, lifethreatening condition, radioiodine I-131 might be a treatment option.

The chemical effects of radioactive decay arise from (1) transmutation, (2) formation of charged daughter nuclei, (3) recoil of the daughter nuclei, (4) electron “shakeoff” phenomenon and (5) vacancy cascade in decays via electron capture and internal conversion. This review aims to reiterate what has been known for a long time regarding the chemical consequences of radioactive decay and gives a historical perspective to the observations that led to their elucidation. The energetics of the recoil process in each decay mode is discussed in relation to the chemical bond between the decaying nucleus and the parent molecule. Special attention is given to the biological effects of the Auger process following decay by electron capture and internal conversion because of their possible utility in internal radiotherapy.

Background & Objectives: There are many challenges in the execution of targeted therapy in cancer due to tumor heterogeneity between individuals. In case of solid tumors this is one of the reasons as to why genomic analysis from single tumor biopsy specimens underestimate the mutational burdens in such heterogeneous tumors thus contributing to treatment failure and drug resistance. Molecular characteristics redefine tumor classification for molecular targeted therapies ensuring the best patient specific therapies with better specificity and cost effective ratio. Functional imaging like Positron Emission Tomography & Computed Tomography (PET-CT) with 18-F Fluorodeoxyglucose (FDG) has been extensively used in oncology to assess the glucose metabolism in tumor cells since long. It has been further redefined to use other radiopharmaceutical targets capable of tumor characterization, microenvironment, angiogenesis, proliferation, apoptosis, receptor expression and few others. Among these the receptor expression in tumors have been studied in detail and specific imaging probes have been developed for imaging with either Single Photon Emission Computed Tomography (SPECT-CT) or PET-CT. Combination of these diagnostic tool with the same vector has permitted an easy switch from diagnosis to therapy using a therapeutic radionuclide when such expression is documented. Thus in Nuclear Medicine the concept of Theranostics have been utilized with ease and successfully implemented the theranostic concept and has become a valid example of personalized and precision medicine. Imaging and therapy of thyroid cancer, neuroendocrine tumors and castration resistant prostate cancer are current examples of this concept. Conclusion: Molecular imaging has high potential to link target identification with therapy and thus to personalize it. It also has a very high potential for in-vivo tissue characterization, to improve prediction, prognostication, road map for biopsy and monitoring of therapy.

Background and Objectives: We are witnessing an era of increased clinical interest in metastatic castration-resistant prostate cancer, both in terms of treatment and also in terms of imaging options. This surge of interest is attributed to the recent developments in treatments for metastatic prostate cancer that are able to confer a significant survival advantage. We are therefore, anticipating an increase in the number of patients that we need to treat at this disease stage. Imaging is undoubtedly crucial in monitoring disease response to treatment and progression. Methods: We have reviewed the recent literature using the following search terms: “metastatic prostate cancer”, “castration-resistant”, “bone metastases”, “bone scan”, “abiraterone”, “enzalutamide”. Results: Bone scintigraphy has evolved recently with new and more sensitive tracers that can accurately diagnose even low volume disease progression. MRI has an established role in the diagnosis of spinal cord compression. Conclusion: Metastatic, castration-resistant prostate cancer is a discrete and different phase of prostate cancer with newer agents that have shown great promise in controlling the disease and offering a survival benefit for patients. Recommendations regarding the choice of imaging, trigger points for repeating imaging and intervals between imaging are still under development for this phase of the disease especially for patients treated with new androgen targeted agents.

Background: Due to the spread of mammographic screening programs, a constant increase of clinically-occult breast cancer diagnosis has been registered. A correct approach to nonpalpable breast lesions requires an accurate intra-operative localization in order to achieve a complete surgical resection. The aim of this paper is to describe the state of the art of the US-guided procedures such as Radio-guided Occult Lesion Localization (ROLL) and Radio-guided Seed Localization (RSL) in comparison to the most widely adopted Wire-Guided Localization (WGL). Methods: Links to full text papers and abstracts published in the last 25 years regarding localization of non-palpable breast lesions were researched using PubMed service of US National Library of Medicine. Using the term “non-palpable breast lesions localization”, different localization techniques were considered and analyzed. Human studies, published in English, French, German, Italian, and Spanish in journals with an impact factor index, were taken into account, independently of the type of article (clinical trial, review, editorial, etc.) or radiopharmaceutical used. Since the aim was to assess the clinical value of the procedures, a higher relevance was assigned to studies with significantly high number of patients and to those comparing at least two localization techniques. The reliability of each technique was evaluated taking into account several parameters such as correlation index between two localization procedures, risk of complications, lesion margin involvement and rate re-operation. Conclusions: Since their introduction in clinical practice, several randomized clinical trials and meta-analyses showed the accuracy and reliability of radio-guided procedures performed under ultrasonographic guidance. ROLL and RSL offer a practical approach to the management of clinically-occult breast lesions.

Background and Objective: In the last decade, an increasing number of positron emission tomography / magnetic resonance (PET/MR) tomographs were installed and many clinical studies were performed in the neurological field. Methods: Although PET/MR has many favorable properties to support the application in brain imaging, attenuation correction, and therefore accurate quantification, is a problem that still requires optimal solution. Results: In this review we have summarized the three main methods that are currently used to correct attenuation in PET/MR, namely atlas- or template-based methods, segmentation-based methods, and reconstruction-based methods. There is currently active ongoing research to refine available methods and improvements are reasonably expected in the next years. Clinical studies using PET/MR focused mainly on neurodegenerative and neurooncological disorders. PET/MR hybrids tomographs provided promising scientific results and were logistically more convenient for patients. Additionally, in order to explore all potential clinical benefits of this hybrid technology, the design and development of multimodal contrast agents has constantly increased the attention of radiochemists. Many PET/MR dual probes have been already devised, particularly in the nanotechnology field, sometimes preceding the identification of a clear diagnostic application in medicine. Conclusion: In the near future, we predict more clinical studies as the availability of PET/MR will further increase and new tracers for neurodegenerative disorders will accept broader clinical acceptance.

Background: To evaluate the efficacy of 11C-choline PET/CT (CHO-PET/CT) based helical tomotherapy (HTT) as a therapeutic approach for bone metastases in recurrent prostate cancer (PCa) patients. Methods: This retrospective study includes 20 PCa patients (median age: 67; range: 51-80 years) presenting biochemical relapse after primary treatment who underwent CHO-PET/CT based HTT on positive bone metastases from December 2007 to June 2014. The effectiveness of HTT has been assessed with biochemical response at 3/6/12 months, biochemical relapse free survival (bRFS) and overall survival (OS) at 2 years. Toxicity has also been considered and assessed according to Common Terminology Criteria for Adverse Events (CTCAE). Results: All patients presented a relapse at the time of CHO-PET/CT at bone level. In addition 15/20 (75%) also at lymph nodes (LNs) level (total lesions= 54). All patients underwent HTT on bone metastases and 19/20 concomitantly on prostatic bed and LNs. The median follow-up from CHO-PET/CT was 2 years (range: 1-7 years). At 3 months after the beginning of HTT treatment complete or partial biochemical response occurred in 79% of patients, at 6 months in 82% and at 12 months in 63% of patients. bRFS and OS at 2 years were 50% and 55% of patients, respectively. Patients presented mostly grade 1 or 2 toxicity according to CTCAE. The only grade 3 late toxicity has been observed in one patient. Conclusion: CHO-PET/CT based HTT is a suitable therapeutic approach in patients with recurrent PCa presenting bone metastases with a medium-low toxicity.

Background: Glycine N-methyltransferase is an enzyme overexpressed in some neoplastic tissues. It catalyses the methylation of glycine using S-adenosyl methionine (SAM or AdoMet) as substrate. SAM is involved in a great variety of biochemical processes, including transmethylation reactions. Thus, [11C]SAM could be used to evaluate transmethylation activity in tumours. The only method reported for [11C]SAM synthesis is an enzymatic process with several limitations. We propose a new chemical method to obtain [11C]SAM, through a one-pot synthesis. Method: The optimization of [11C]SAM synthesis was carried out in the automated TRACERlab® FX C Pro module. Different labelling conditions were performed varying methylating agent, precursor amount, temperature and reaction time. The compound was purified using a semipreparative HPLC. Radiochemical stability, lipophilicity and plasma protein binding were evaluated. Results: The optimum labelling conditions were [11C]CH3OTf as the methylating agent, 5 mg of precursor dissolved in formic acid at 60 °C for 1 minute. [11C]SAM was obtained as a diastereomeric mixture. Three batches were produced and quality control was performed according to specifications. [11C]SAM was stable in final formulation and in plasma. Log POCT obtained for [11C]SAM was (-2,01 ± 0,07) (n=4), and its value for plasma protein binding was low. Conclusion: A new chemical method to produce [11C]SAM was optimized. The radiotracer was obtained as a diastereomeric mixture with a 53:47 [(R,S)-isomer: (S,S)-isomer] ratio. The compound was within the quality control specifications. In vitro stability was verified. This compound is suitable to perform preclinical and clinical evaluations.

Background: The red fluorescent dye Sulforhodamine 101 (SR101) has been used in neuroscience research as a useful tool for staining of astrocytes, since it has been reported as a marker of astroglia in the neocortex of rodents in vivo. The aim of this work is to label SR101 with positron emission radionuclides, in order to provide a radiotracer to study its biological behavior. This is the first attempt to label SR101 by [18F], using a chemical derivatization via a sulfonamidelinker and a commercially available platform. Methods: The synthesis of SR101 N-(3-Bromopropyl) sulfonamide and SR101 N-(3- Fluoropropyl) sulfonamide (2B-SRF101) was carried out. The radiosynthesis of SR101 N-(3- [18F]Fluoropropyl) sulfonamide ([18F]2B-SRF101) was performed in a TRACERlab® FX-FN. Different labeling conditions were tested. Three pilot batches were produced and quality control was performed. Lipophilicity, plasma protein binding and radiochemical stability of [18F]2BSRF101 in final formulation and in plasma were determined. Results: SR101 N-(3-Bromopropyl) sulfonamide was synthetized as a precursor for radiolabeling with [18F]. 2B-SRF101 was prepared for analytical purpose. [18F]2B-SRF101 was obtained with radiochemical purity of (97.0 ± 0.6%). The yield of the whole synthesis was (11.9 ± 1.7 %), nondecay corrected. [18F]2B-SRF101 was found to be stable in final formulation and in plasma. The octanol-water partition coefficient was (Log POCT = 1.88 ± 0.14). The product showed a high percentage of plasma protein binding. Conclusions: The derivatization of SR101 via sulfonamide-linker and the first radiosynthesis of [18 F]2B-SRF101 were performed. It was obtained in accordance with quality control specifications. In vitro stability studies verified that [18F]2B-SRF101 was suitable for preclinical evaluations.