Hospital Radiopharmacy Research Articles

Formulation of patient dose of [177Lu]Lu-Trastuzumab using in-house developed freeze-dried kit: A path forward for clinical translation.

Trastuzumab is a US-FDA-approved humanized monoclonal antibody used for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The aim of the present work is to optimize a freeze-dried formulation of DOTA-Trastuzumab conjugate for the preparation of patient doses of [177Lu]Lu-Trastuzumab for radioimmunotherapy of breast cancer. The formulation of [177Lu]Lu-Trastuzumab usually takes a long time, and thus, such a process is not suitable for the routine preparation of this agent in hospital radiopharmacies. To circumvent this, a pre-synthesized DOTA-Trastuzumab conjugate as a freeze-dried formulation is proposed. In the present work, DOTA-Trastuzumab conjugate was subjected to a freeze-drying process after the addition of optimized amounts of radioprotectant and cryoprotectant. [177Lu]Lu-DOTA-Trastuzumab was prepared by incubating the lyophilized powder of the kit vial with medium-specific activity 177LuCl3. The final radiochemical purity of [177Lu]Lu-DOTA-Trastuzumab, prepared using freeze-dried kit, was determined to be >95%. To ascertain the reproducibility of the procedure, six consecutive batches of the freeze-dried formulation were prepared, radiolabeled, and evaluated by carrying out both in vitro and ex vivo studies. The consistency of the results of all the six consecutive batches confirmed the robustness and utility of the in-house optimized freeze-dried formulation for the preparation of patient doses of [177Lu]Lu-Trastuzumab at hospital radiopharmacies.

Radiosynthesis Standardization and Preclinical Assessment of the [68Ga]Ga-DOTA-Ubiquicidin29-41: A Translational Study Targeting Differential Diagnosis of Infectious Processes.

Human bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies. However, radiopharmaceuticals that are available for routine assessments are not specific to differentiating infectious from aseptic inflammatory processes. In this context, [68Ga]Ga-DOTA-Ubiquicidin29-41 was synthesized using an automated module and radiochemical; in vivo and in vitro studies were performed. The radiopharmaceutical remained stable in saline (up to 180 min) and in rodent serum (up to 120 min) with radiochemical purities > 99 and 95%, respectively. Partition coefficient and serum protein binding at 60 min were determined (-3.63 ± 0.17 and 44.06 ± 1.88%, respectively). Ex vivo biodistribution, as well as in vivo microPET/CT images in mice, showed rapid blood clearance with renal excretion and reduced uptake in other organs in Staphylococcus aureus-infected animals. Higher uptake was observed in the target as compared to the non-target tissue (p < 0.0001) at 60 min post administration. The presented in-human clinical case demonstrates uptake of the radiopharmaceutical by Staphyloccocus aureus bacteria. These results indicate the potential of [68Ga]Ga-DOTA-Ubiquicidin29-41 as a radiopharmaceutical that can be obtained in a hospital radiopharmacy for the diagnosis of infectious processes using PET/CT.

188 Re-N-DEDC Lipiodol for Treatment of Hepatocellular Carcinoma (HCC)-A Clinical and Prospective Study to Assess In-Vivo Distribution in Patients and Clinical Feasibility of Therapy.

Objective The incidence of inoperable hepatocellular carcinoma (HCC) with/without malignant portal vein thrombosis (PVT) is increasing in India for the last decade; thus, Bhabha Atomic Research Centre (BARC), Mumbai, India, developed diethydithiocarbamate (DEDC), a new transarterial radionuclide therapy (TART) agent. 188 Re-N-DEDC lipiodol is an emerging radiotherapeutic agent for inoperable HCC treatment due to its simple and onsite labeling procedure, cost-effectiveness, and least radiation-induced side effects. This study aimed to evaluate in-vivo biodistribution and clinical feasibility of 188 Re-N-DEDC lipiodol TART in HCC and optimization of labeling procedure to assess post-labeling stability and radiochemical yield of labeled lipiodol with 188 Re-N-DEDC complex. Materials and Methods DEDC kits were obtained as gift from BARC, Mumbai. Therapy was given to 31 HCC patients. Post-therapy planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging were performed to see tumor uptake and biodistribution. Clinical feasibility and toxicity were decided by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0). Statistical Analysis Descriptive statistics was done for data using SPSS v22. Values was expressed as mean ± standard deviation or median with range. Results Post-therapy planar and SPECT/CT imaging showed radiotracer localization in hepatic lesions. Few patients showed lungs uptake due to hepato-pulmonary shunt (lung shunt < 10%). Maximum clearance was observed through urinary tract with very less elimination through hepatobiliary route due to slow rate of leaching of tracer. No patient showed myelosuppression or any other long-term toxicity over median follow-up of 6 months. Mean overall % radiochemical yield of 188 Re-N-DEDC lipiodol was 86.04 ± 2.35%. The complex 188 Re-N-DEDC was found to be stable at 37°C under sterile condition over a period of 1 hour without any significant change on the % radiochemical purity (90.83 ± 3.24%, 89.78 ± 3.67%, 89.22 ± 3.77% at 0, 0.5, 1 hours, respectively). Conclusion Human biodistribution showed very high retention of radiotracer in hepatic lesions with no long-term toxicity with this therapy. The kit preparation procedure is ideally suited for a busy hospital radio-pharmacy. By this procedure, 188 Re-N-DEDC lipiodol can be prepared in high radiochemical yield within a short time (∼45 minutes). Thus, 188 Re-N-DEDC lipiodol can be considered for TART in advanced and/or intermediate HCC.

Development of the 99mTc-Labelled SST2 Antagonist TECANT-1 for a First-in-Man Multicentre Clinical Study

Broad availability and cost-effectiveness of 99Mo/99mTc generators worldwide support the use, and thus the development, of novel 99mTc-labelled radiopharmaceuticals. In recent years, preclinical and clinical developments for neuroendocrine neoplasms patient management focused on somatostatin receptor subtype 2 (SST2) antagonists, mainly due to their superiority in SST2-tumour targeting and improved diagnostic sensitivity over agonists. The goal of this work was to provide a reliable method for facile preparation of a 99mTc-labelled SST2 antagonist, [99mTc]Tc-TECANT-1, in a hospital radiopharmacy setting, suitable for a multi-centre clinical trial. To ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration, a freeze-dried three-vial kit was developed. The final composition of the kit was established based on the radiolabelling results obtained during the optimisation process, in which variables such as precursor content, pH and buffer, as well as kit formulations, were tested. Finally, the prepared GMP-grade batches met all predefined specification parameters together with long-term kit stability and stability of the product [99mTc]Tc-TECANT-1. Furthermore, the selected precursor content complies with micro-dosing, based on an extended single-dose toxicity study, where histopathology NOEL was established at 0.5 mg/kg BW, being more than 1000 times higher than the planned human dose of 20 µg. In conclusion, [99mTc]Tc-TECANT-1 is suitable to be advanced into a first-in-human clinical trial.

A robust lyophilized kit for convenient one-step formulation of [68Ga]Ga-DOTA-E−[c(RGDfK)]2 in hospital radiopharmacy for clinical PET imaging

The present article describes the development of robust lyophilized kit for convenient formulation of [68Ga]Ga-DOTA-E−[c(RGDfK)]2 (E = glutamic acid, R = arginine, G = glycine, D = aspartic acid, f = phenylalanine, K = lysine) radiopharmaceutical for clinical use in non-invasive monitoring of malignancies overexpressing integrin αvβ3 receptors. Five batches of the kit were prepared with optimized kit contents, all of which showed high 68Ga-radiolabeling yield (>98%). Pre-clinical evaluation of the [68Ga]Ga-radiotracer in SCID mice bearing FTC133 tumour exhibited significant accumulation in the tumor xenograft. Preliminary human clinical investigation carried out in a 60 year old male patient with metastatic lung cancer revealed high radiotracer uptake in the tumor along with satisfactory target to non-target contrast. The developed kit formulation also showed a long shelf-life of at least 12 months on storage at 0 °C. All these results point towards the promising attributes of the developed kit formulation for convenient preparation of [68Ga]Ga-DOTA-E−[c(RGDfK)]2 for routine clinical use.

Preparation of Patient Doses of [177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA-617 with Carrier Added (CA) and No Carrier Added (NCA) 177Lu.

[177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA-617 used for targeted radionuclide therapy are very often prepared in the hospital radiopharmacy. The preparation parameters vary depending upon the specific activity of the 177Lu used. The aim of this study was to develop optimized protocols to be used in the nuclear medicine department for the preparation of patient doses of the above radiopharmaceuticals. 177Lu (CA and NCA) were used for radiolabeling DOTATATE and PSMA-617. Parameters studied are 177Lu of different specific activity and different peptide concentrations and two different buffer systems. Paper and thin layer chromatography systems were used for estimating the radiochemical yield as well as radiochemical purity. Solid-phase extraction was used for the purification of the labeled tracers. [177Lu]Lu-DOTATATE was prepared with CA 177Lu (n = 13) and NCA177Lu (n = 6). Four batches each of [177Lu]Lu-PSMA-617 were prepared using CA and NCA 177Lu. Radiochemical yields > 80% and final product with less than < 1% radiochemical impurity could be obtained in all batches which were used for therapy. Robust protocols for the preparation of clinical doses of [177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA-617 were developed and used for the preparation of clinical doses. The quality of the SPECT images of both the tracers are consistent with the expected uptake in respective diseases.

QUALITY ASSURANCE AND QUALITY CONTROL OF RADIOPHARMACEUTICALS: AN OVERVIEW

Objective: Radiopharmacy is a special field of pharmacy that examines, develops, conducts quality controls, deals with distribution and application of pharmaceutical forms called radiopharmaceuticals that are used for diagnostic and therapeutic purposes, carrying pharmaceutical and radioactive properties together. Radiopharmaceuticals contain radionuclides. This is the most important difference that distinguishes radiopharmaceuticals from other conventional drugs. Since radiopharmaceuticals are administered to humans, they must be sterile, pyrogen-free, isotonic, isohydric, and subject to all quality control tests required for conventional drug. Also, additional quality control tests are required due to radionuclide they contain. In this review, quality control tests applied to radiopharmaceuticals, hospital radiopharmacy laboratory types and Good Radiopharmacy Practices (GRP) will be discussed. Result and Discussion: Radiopharmaceuticals should be prepared in accordance with standards specified in relevant sections of pharmacopoeias. For each series of radiopharmaceuticals, tests prescribed in the pharmacopoeias and records must be kept. Production and preparation of radiopharmaceuticals should be carried out in accordance with Good Manufacturing Practices for sterile preparations and GRP for radioactive products. However, radiopharmaceuticals that pass quality control tests can be administered to patients after dose measurements are made in dose calibrators. Thus, the patient's safety and benefit are maximized, while the risk is minimized. Some radiopharmaceuticals with a short half-life are used before quality control tests are completed. In this case, the effectiveness and continuation of the quality assurance system should be tested at appropriate intervals. According to procedures performed by hospital radiopharmacy laboratories, international standards are determined as Level IA/B, Level IIA/B and Level IIIA/B/C. Quality assurance of radiopharmaceuticals is provided by a sufficient number of trained personnel within the scope of GRP, devices that have been calibrated and controlled, appropriate substances and a working order in which tests determined at each stage are made and results are recorded accurately and regularly.

Radiopharmaceutical good practices: Regulation between hospital and industry.

Radiopharmaceutical practices are divided into large-scale industrial manufacturing and small-scale "in-house" hospital radiopharmacy unit. The recent evolution of nuclear medicine involves deep consequences in this ever-present regulatory state, and hospital radiopharmacy units cannot be considered as contract manufacturing organizations (CMO). This review provides an updated status report of the official (and non-official) guidelines supporting the regulations required to meet hospital and industry common radiopharmaceutical manufacturing standards to facilitate the current and future innovative radiopharmaceutical development.

Experience with radiopharmacy information system

BackgroundThe efficient management of hospital radiopharmacy is very important for a good workflow in nuclear medicine and essential to ensure the correct traceability of the radiopharmaceuticals administered to patients. In the hospital radiopharmacy of our nuclear medicine department, it was developed and implemented a radiopharmacy information system (Radiolab).ResultsFrom its implementation, important additional functionalities have been added to this software application, according to our requirements and according as well to some of the specific requirements proposed in a recently published consensual tool for validating radiopharmacy software. After more than ten years from the implementation of this software application, it has been analysed its contribution to our hospital radiopharmacy and nuclear medicine department.ConclusionsAs a result, this radiopharmacy information system provides comprehensive management of our hospital radiopharmacy in an efficient way, and reliable traceability of every dose of radiopharmaceutical administered in our nuclear medicine department.

Implementation of the failure modes and effects analysis in a Hospital Radiopharmacy Unit

AimThe aim of this study is the implementation in a Hospital Radiopharmacy Unit of a risk analysis methodology in order to proactively identify possible failure modes and prioritize corrective measures. Materials and methodsBy means of the failure modes and effects analysis (FMEA), the possible failure modes of each of the stages of the processes of prescription, preparation, and administration of radiopharmaceuticals for diagnostic and therapy were identified. From the variables of severity, probability and detectability, the risk was quantified using the Risk Priority Number (RPN) for each failure mode, sub-process, and type of radiopharmaceutical. Improvement measures were established and the reduction in the RPN value was calculated. ResultsA total of 96 failure modes were identified (58 for diagnostic radiopharmaceuticals and 38 for therapy). Biunivocal identification of the patient with the radiopharmaceutical is the failure mode with the highest RPN (60) and the radiolabeling cell sub-process the one that has the highest risk (RPN 286). As a result of the improvement measures, the overall RPN was reduced by 22% for diagnostic radiopharmaceuticals and 20% for therapy. This reduction would be 46% and 31% respectively if radiopharmacy software and a barcode technology in the administration were implemented. ConclusionsThe application of the FMEA methodology as a risk analysis tool allows to identify the critical points of the processes related to radiopharmaceuticals and prioritize measures to reduce the risk.

Clinical Dose Preparation of [177Lu]Lu-DOTA-Pertuzumab Using Medium Specific Activity [177Lu]LuCl3 for Radioimmunotherapy of Breast and Epithelial Ovarian Cancers, with HER2 Receptor Overexpression.

Background: The overexpression of human epidermal growth factor receptor 2 (HER2) is commonly associated with metastatic breast cancer and epithelial ovarian cancer. The U.S. Food and Drug Administration (FDA) has approved Trastuzumab as an anti-HER2 agent for the metastatic breast and epithelial ovarian cancer. However, Trastuzumab has severe limitations in the treatment of metastatic breast cancer associated with ligand-dependent dimerization of HER2 receptor at the extracellular domain-II (ECD-II) region. The therapeutic approach in combination of pertuzumab and trastuzumab is found to be effective in preventing HER2 dimerization at the ECD-II region. The radioimmunotherapeutic approach, utilizing both these anti-HER2 agents (trastuzumab/pertuzumab), radiolabeled with [177Lu]Lu3+, has proved to be clinically efficacious with promising potential. Toward this, the formulation for clinical doses of [177Lu]Lu-DOTA-pertuzumab has been optimized using medium specific activity (0.81 GBq/μg) [177Lu]LuCl3. Materials and Methods: Preconcentrated pertuzumab was conjugated with p-NCS-benzyl-DOTA. Purified DOTA-benzyl-pertuzumab conjugate was radiolabeled with carrier-added [177Lu]LuCl3. Quality control parameters were evaluated for the [177Lu]Lu-DOTA-pertuzumab. In vivo biodistribution was carried out at different time points postadministration. Specific cell binding, immunoreactivity, and internalization were investigated by using SKOV3 and SKBR3 cells. Results: In this study, the authors reported a consistent and reproducible protocol for clinical dose formulations of [177Lu]Lu-DOTA-pertuzumab, with a radiochemical yield of 86.67% ± 1.03% and radiochemical purity (RCP) of 99.36% ± 0.36% (n = 10). Preclinical cell binding studies of [177Lu]Lu-DOTA-pertuzumab revealed specific binding with SKOV3 and SKBR3 cells up to 24.4% ± 1.4% and 23.2% ± 0.8%, respectively. The uptakes in SKOV3- and SKBR3-xenografted tumor in severe combined immunodeficiency mice were observed to be 25.9% ± 0.8% and 25.2% ± 1.2% ID/g at 48 and 120 h postinjection, respectively. Conclusions: A protocol was optimized for the preparation of ready-to-use clinical dose of [177Lu]Lu-DOTA-pertuzumab, in hospital radiopharmacy settings. The retention of RCP of the radiopharmaceutical, on storage in saline and serum, at -20°C, up to 120 h postradiolabeling, confirmed its in vitro stability.

Implementación del análisis modal de fallos y efectos en una Unidad de Radiofarmacia Hospitalaria

AimThe aim of this study is the implementation in a Hospital Radiopharmacy Unit of a risk analysis methodology in order to proactively identify possible failure modes and prioritize corrective measures. Materials and methodsBy means of the failure modes and effects analysis (FMEA), the possible failure modes of each of the stages of the processes of prescription, preparation, and administration of radiopharmaceuticals for diagnostic and therapy were identified. From the variables of severity, probability and detectability, the risk was quantified using the Risk Priority Number (RPN) for each failure mode, sub-process, and type of radiopharmaceutical. Improvement measures were established and the reduction in the RPN value was calculated. ResultsA total of 96 failure modes were identified (58 for diagnostic radiopharmaceuticals and 38 for therapy). Biunivocal identification of the patient with the radiopharmaceutical is the failure mode with the highest RPN (60) and the radiolabeling cell sub-process the one that has the highest risk (RPN 286). As a result of the improvement measures, the overall RPN was reduced by 22% for diagnostic radiopharmaceuticals and 20% for therapy. This reduction would be 46% and 31% respectively if radiopharmacy software and a barcode technology in the administration were implemented. ConclusionsThe application of the FMEA methodology as a risk analysis tool allows to identify the critical points of the processes related to radiopharmaceuticals and prioritize measures to reduce the risk.

Performance and long-term consistency of five Galliform 68Ge/68Ga generators used for clinical Ga-68 preparations over a 4 year period.

Gallium-68 is a positron emitter for PET applications that can be produced without cyclotron by a germanium (Ge-68) chloride/gallium (Ga-68) chloride generator. Short half-life (67.71 min) of Ga-68, matching pharmacokinetic properties of small biomolecules, facilitates isotope utilization in compounding radiopharmaceuticals for PET imaging. The increasing cost of good manufacturing practice-compliant generators has strengthened the need for radionuclide efficient use by planning specific radiopharmaceutical sessions during the week, careful maintenance of the generator and achievement of high labeling yield and radiochemical purity (RCP) of the radiolabeled molecules. The aim of this study was to evaluate the annual performance of five consecutive 68Ge/68Ga generators used for small-scale preparations of 68Ga-radiopharmaceuticals. To assess the long-term efficiency of isotope production we measured the weekly elution yield. To assess process efficiency we measured elution yield, labeling yield and RCP of four radiopharmaceutical preparations (68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68Ga-PENTIXAFOR and 68Ga-DOTATATE). The annual mean elution yield of the generators was 74.7%, higher than that indicated by the manufacturer, and it never went below 65%. The Ge-68 level in the final products was under the detection limits in all the produced batches (mean value 0.0000048%). The RCP of radiopharmaceuticals determined by high-performance liquid chromatography was 98 ± 0.22%. The mean yield of radiolabelling was 64.68, 68.71, 57 and 63.68% for 68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68GaPENTIXAFOR and 68Ga-DOTATATE. The ability to prepare in the hospital radiopharmacy high-purity and pharmaceutically acceptable 68Ga-radiolabeled probes on a routine basis facilitates patient access to precision imaging for clinical and research aims.

Fully Automated Synthesis of Nitrogen-13-NH3 by SHIs HM-18 Cyclotron and Dedicated Module for Routine Clinical Studies

Aims:The production of nitrogen-13 (13N)-NH3 by ethanol method using automated synthesizer and accessing the production yield, quality control for clinical application.Context:13N, together with 18F, 15O, and 11C, is one of the positron emitters that can be produced on the multi-gigabecquerel scale in biomedical cyclotrons. (13N)-ammonia is frequently used for cardiac PET studies. It is widely applied for the evaluation of myocardial perfusion in the clinical assessment of cardiac disorders. Simple, fast, and reliable preparation methods have contributed to the routine application of this tracer. Although only two methods are available, a challenge remains to adopt a more efficient and consistent approach to its production. For clinical application, routine production of this tracer is mandatory in compliance with regulatory guidelines. Being at hospital radiopharmacy it is our responsibility to support the clinical service with uninterrupted production and supply of (13N)-NH3.Materials and Methods: The chemicals were used commercially available from Sigma Aldrich, India, Ltd., and Fisher Scientific, India, Ltd. (Mumbai, India), Sep-Pak CM cartridges (Waters India, Pvt., Ltd.,). Radio-thin layer chromatography was carried out using aluminum sheets precoated with silica gel 60 F254 (E. Merck, India).Results:The protocol developed with MPS-100 synthesizer yield (13N)-NH395–97% (EOB) with a synthesis time of around 7 min.Conclusions:With the installation of HM-18 cyclotron at our hospital, center is capable to produce (13N)-NH3 of good yield and purity through the ethanol method, for mycocardial perfusion studies. Our protocol is simple, reproducible, and robust.

Therapeutic Multidose Preparation of a Ready-to-Use 177Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy.

Introduction: [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 has emerged as a promising radiopharmaceutical for targeting PSMA in metastatic castrate-resistant prostate carcinoma (mCRPC). We have optimized the radiolabeling protocol for a multidose formulation (27-28.8 GBq equivalent to 6-7 patient-doses) of [177Lu]Lu-PSMA-617 using [177Lu]Lu3+ produced via 176Lu(n,γ)177Lu route with moderate specific activity (0.66-0.81 GBq/μg). Methods: [177Lu]Lu-PSMA-617 was synthesized using moderate specific activity [177Lu]LuCl3 (0.74 GBq/μg) with PSMA-617 having metal-to-ligand molar ratio ∼1: 2.5 in CH3COONH4 buffer (0.1 M) containing gentisic acid at pH 4.0-4.5. Human prostate carcinoma cell line LNCaP cell (high PSMA expression) was used for in vitro cell-binding studies and generating tumor xenograft models in nude mice for tissue biodistribution studies. Several batches of the present formulation have been clinically administered in mCRPC patients (single patient dose: 4.44-5.55 GBq per cycle). Results: In this study we report a consistent and reproducible protocol for multidose formulations of [177Lu]Lu-PSMA-617 for adopting in a hospital radiopharmacy setting. Although the radiochemical yield of [177Lu]Lu-PSMA-617 was found to be 97.30% ± 1.03%, the radiochemical purity was 98.24% ± 0.50% (n = 19). In vitro and serum stability of [177Lu]Lu-PSMA-617 was retained up to 72 and 120 h after radiolabeling and upon storage at -20°C with a radioactive concentration between 0.37 and 0.74 GBq/mL upon using stabilizer concentration as low as 43-48 μg/mCi. Preclinical cell-binding studies of [177Lu]Lu-PSMA-617 revealed specific binding with LNCaP cells of 17.4% ± 2.4%. The uptake in LnCaP xenografted tumor (nude mice) was 7.5 ± 2.6% ID/g for ∼1.5-2.0 cm3 tumor volume at 24-h post-injection. Post-therapy (24 h) SPECT image of mCRPC patients with prior orchidectomy and various hormone therapy showed specific localization of [177Lu]Lu-PSMA-617 in the tumor region. Conclusions: Formulation of a ready-to-use multidose formulation of [177Lu]Lu-PSMA-617 was successfully achieved and the procedure was optimized for routine preparation at a hospital radiopharmacy set-up. High degree of localization of [177Lu]Lu-PSMA-617 in post-therapy SPECT scan and the post-therapeutic response confirms its therapeutic efficacy. Clinical Trials.gov ID: RPC/51/Minutes/Final dated 16th October, 2019.

Transferability of a two-strip method for the quality control of technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3)

ObjectivesTechnetium-99m mercapto-acetyl-triglycine ([99mTc]Tc-MAG3) is a radiopharmaceutical diagnostic agent used in nuclear medicine intended for the exploration of nephrological and urological disorders. Patient safety and reliability of this imaging procedure especially...

Preparation of Rhenium-188-Lipiodol Using Freeze-Dried Kits for Transarterial Radioembolization: An Overview and Experience in a Hospital Radiopharmacy.

Background: Rhenium-188(188Re)-lipiodol is a clinically effective, economically viable radiopharmaceutical for Selective Internal Radiation Therapy of liver cancer. Present study evaluates the performance of three freeze-dried kits with respect to the radiochemistry, quality control, and overall "ease of preparation" aspects in a hospital radiopharmacy. Materials and Methods: Freeze-dried kits of acetylated 4-hexadecyl-4,7-diaza-1,10-decanedithiol (AHDD), super six sulfur (SSS), and diethyl dithiocarbamate (DEDC), obtained commercially or received as gift, were used for the preparation of 188Re-lipiodol using freshly eluted 188Re-sodium perrhenate from commercial Tungsten-188/188Re generator following recommended procedures. Results: The overall yield of 188Re-lipiodol prepared using AHDD Kit, SSS Kit, and DEDC Kit was 74.82% ± 3.3%, 87.55% ± 4.8%, and 76.38% ± 4.6%, respectively. Observed radiochemical purity (RCP) of 188Re-lipiodol prepared using these kits was 88.65% ± 2.8%, 92.92% ± 3.0%, and 91.38% ± 3.0%, respectively. Using a modified version of the DEDC Kits, overall yield of 87.17% ± 2.7% and RCP of 95.43% ± 2.3% could be achieved. Conclusions: While all three freeze-dried kits can be used for the preparation of 188Re-lipiodol in >70% overall yield, the modified version of DEDC Kits has some advantages in terms of preparation time and volume of Rhenium-188 activity that can be added to the kit vial. The latter feature of the DEDC Kit is particularly useful for patient dose preparation with 188Re activity of low radioactive concentration.

Establishing the [18F]-FDG Production via Two Different Automated Synthesizers for Routine Clinical Studies: Our Institutional Experiences of 4 years.

Introduction:[18F]-Fluorodeoxyglucose ([18F]-FDG) is the most widely used positron-emission tomography tracer used for imaging in clinical studies such as early detection of cancer or its malignancies, quantifications, staging, and restaging of several malignancies. For clinical application, routine production of this tracer is mandatory in compliance to regulatory guidelines. Several dedicated commercial synthesizers are currently used for producing[18F]-FDG for clinical usage. Being at hospital radiopharmacy, it is our responsibility and duty to support the clinical service with uninterrupted production and supply of [18F]-FDG. This document describes the production of [18F]-FDG using two different automated synthesizers in terms of its production yield, time of synthesis, and analyze the quality control (QC) of the produced [18F]-FDG.Materials and Methods:The precursor, mannose triflate ultra-pure, authentic nonradioactive standard FDG and [18O]-water were obtained from ABX, Germany. Solvents and reagents were purchased from Sigma Aldrich India Ltd. and Fisher Scientific India Ltd., (Mumbai, Maharashtra, India).Results:The protocol developed for the synthesis with MPS-100 synthesizer yield of [18F]-FDG is approximate about 45% End of Bombardment (EOB) with synthesis time of around 35 min, whereas with F300E synthesizer it is around 60% with synthesis time of 25 min. The quality of the tracer produced by both synthesizers is at par with the QC parameter for clinical applications.Conclusions:Finally, we have developed the production using two automated synthesis modules which have the capability to produce [18F]-FDG, to do the patient studies in good yield and purity. Our protocol is simple, reproducible, and robust.

Guideline on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals

This guideline on current good radiopharmacy practice (cGRPP) for small-scale preparation of radiopharmaceuticals represents the view of the Radiopharmacy Committee of the European Association of Nuclear Medicine (EANM). The guideline is laid out in the format of the EU Good Manufacturing Practice (GMP) guidelines as defined in EudraLex volume 4. It is intended for non-commercial sites such as hospital radiopharmacies, nuclear medicine departments, research PET centres and in general any healthcare establishments. In the first section, general aspects which are applicable to all levels of operations are discussed. The second section discusses the preparation of small-scale radiopharmaceuticals (SSRP) using licensed generators and kits. Finally, the third section goes into the more complex preparation of SSRP from non-licensed starting materials, often requiring a purification step and sterile filtration. The intention is that the guideline will assist radiopharmacies in the preparation of diagnostic and therapeutic SSRP’s safe for human administration.

A kit-based aluminium-[18F]fluoride approach to radiolabelled microbubbles.

The production of 18F-labelled microbubbles (MBs) via the aluminium-[18F]fluoride ([18F]AlF) radiolabelling method and facile inverse-electron-demand Diels–Alder (IEDDA) ‘click’ chemistry is reported. An [18F]AlF-NODA-labelled tetrazine was synthesised in excellent radiochemical yield (>95% RCY) and efficiently conjugated to a trans-cyclooctene (TCO) functionalised phospholipid (40–50% RCY), which was incorporated into MBs (40–50% RCY). To demonstrate the potential of producing 18F-labelled MBs for clinical studies, we also describe a kit-based approach which is amenable for use in a hospital radiopharmacy setting.