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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Overcoming Barriers to Radiopharmaceutical Therapy (RPT): An Overview From the NRG-NCI Working Group on Dosimetry of Radiopharmaceutical Therapy

Radiopharmaceutical therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiation therapy is standard practice. This is not the case, however, in RPT. This NRG (acronym formed from the first letter of the 3 original groups: National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group)-National Cancer Institute Working Group review describes some of the challenges to improving RPT. The main priorities for advancing the field include (1) developing and adopting best practice guidelines for incorporating patient-specific dosimetry for RPT that can be used at both large clinics with substantial resources and more modest clinics that have limited resources, (2) establishing and improving strategies for introducing new radiopharmaceuticals for clinical investigation, (3) developing approaches to address the radiophobia that is associated with the administration of radioactivity for cancer therapy, and (4) solving the financial and logistical issues of expertise and training in the developing field of RPT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

Global Issues of Radiopharmaceutical Access and Availability: a Nuclear Medicine Global Initiative Project

The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging by supporting the practice and application of nuclear medicine. The first project focused on standardization of administered activities in pediatric nuclear medicine and resulted in two manuscripts. For its second project the NMGI chose to explore issues impacting on access and availability of radiopharmaceuticals around the world. Methods: Information was obtained by survey responses from 35 countries on available radioisotopes, radiopharmaceuticals and kits for diagnostic and therapeutic use. Issues impacting on access and availability of radiopharmaceuticals in individual countries were also identified. Results: Detailed information on radiopharmaceuticals utilized in each country, and sources of supply, was evaluated. Responses highlighted problems in access particularly due to the reliance on a sole provider, regulatory issues and reimbursement, as well as issues of facilities and workforce particularly in low- and middle-income countries. Conclusion: Finally, strategies to address access and availability of radiopharmaceuticals are outlined, to enable timely and equitable patient access to nuclear medicine procedures worldwide. In the face of disruptions to global supply chains by the COVID-19 outbreak, renewed focus on ensuring reliable supply of radiopharmaceuticals is a major priority for nuclear medicine practice globally.

43 PARTICLE ACCELERATORS↗
DOE OSTI2025

Synthesis of DOTA-Based 43 Sc Radiopharmaceuticals Using Cyclotron-Produced 43 Sc as Exemplified by [ 43 Sc]Sc-PSMA-617 for PSMA PET Imaging

The implementation of theranostics in oncologic nuclear medicine has exhibited immense potential in improving patient outcomes in prostate cancer with the implementation of [ 68 Ga]Ga-PSMA-11 PET and [ 177 Lu]Lu-PSMA-617 into clinical practice. However, the correlation between radiopharmaceutical biodistributions seen with [ 68 Ga]Ga-PSMA-11 PET imaging and downstream [ 177 Lu]Lu-PSMA-617 therapy remains imperfect. This suggests that prostate cancer theranostics could potentially be further refined through the implementation of true theranostics, tandem pairs of diagnostic and therapeutic radiopharmaceuticals that utilize the same ligand and element, thus yielding identical pharmacokinetics. The radioscandiums are one such group of true theranostic radiopharmaceuticals. The radioscandiums consist of two β+ emitting scandium isotopes ( 43 Sc/ 44 Sc), as well as a β − emitting therapeutic isotope ( 47 Sc), which can all conjugate with PSMA-targeting PSMA-617. This potential has led to extensive investigations into the production of the radioscandiums as well as pre-clinical assessments with several ligands; however, there is a lack of literature extensively describing the complete synthesis of scandium radiopharmaceuticals. which therefore limits the accessibility of radioscandium research in theranostics. As such, this work aims to present an easily translatable protocol for the synthesis of [ 43 Sc]Sc-PSMA-617 from a [ 42 Ca]CaCO 3 starting material, including target formation, nuclear production via 42 Ca(d,n) 43 Sc reaction, chemical separation, radiolabeling, solvent reformulation, and target recycling.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Production of GMP-Compliant Clinical Amounts of Copper-61 Radiopharmaceuticals from Liquid Targets

PET imaging has gained significant momentum in the last few years, especially in the area of oncology, with an increasing focus on metal radioisotopes owing to their versatile chemistry and favourable physical properties. Copper-61 (t1/2 = 3.33 h, 61% β+, Emax = 1.216 MeV) provides unique advantages versus the current clinical standard (i.e., gallium-68) even though, until now, no clinical amounts of 61Cu-based radiopharmaceuticals, other than thiosemicarbazone-based molecules, have been produced. This study aimed to establish a routine production, using a standard medical cyclotron, for a series of widely used somatostatin analogues, currently labelled with gallium-68, that could benefit from the improved characteristics of copper-61. We describe two possible routes to produce the radiopharmaceutical precursor, either from natural zinc or enriched zinc-64 liquid targets and further synthesis of [61Cu]Cu-DOTA-NOC, [61Cu]Cu-DOTA-TOC and [61Cu]Cu-DOTA-TATE with a fully automated GMP-compliant process. The production from enriched targets leads to twice the amount of activity (3.28 ± 0.41 GBq vs. 1.84 ± 0.24 GBq at EOB) and higher radionuclidic purity (99.97% vs. 98.49% at EOB). Our results demonstrate, for the first time, that clinical doses of 61Cu-based radiopharmaceuticals can easily be obtained in centres with a typical biomedical cyclotron optimised to produce 18F-based radiopharmaceuticals.

Fonseca, Alexandra I. (ORCID:000000031924178X)↗
DOE OSTI2021

Current Status of Radiopharmaceutical Therapy

In radiopharmaceutical therapy (RPT), a radionuclide is systemically or locally delivered with the goal of targeting and delivering radiation to cancer cells while minimizing radiation exposure to untargeted cells. Examples of current RPTs include thyroid ablation with the administration of {sup 131}I, treatment of liver cancer with {sup 90}Y microspheres, the treatment of bony metastases with {sup 223}Ra, and the treatment of neuroendocrine tumors with {sup 177}Lu-DOTATATE. New RPTs are being developed where radionuclides are incorporated into systemic targeted therapies. To assure that RPT is appropriately implemented, advances in targeting need to be matched with advances in quantitative imaging and dosimetry methods. Currently, radiopharmaceutical therapy is administered by intravenous or locoregional injection, and the treatment planning has typically been implemented like chemotherapy, where the activity administered is either fixed or based on a patient’s body weight or body surface area. RPT pharmacokinetics are measurable by quantitative imaging and are known to vary across patients, both in tumors and normal tissues. Therefore, fixed or weight-based activity prescriptions are not currently optimized to deliver a cytotoxic dose to targets while remaining within the tolerance dose of organs at risk. Methods that provide dose estimates to individual patients rather than to reference geometries are needed to assess and adjust the injected RPT dose. Accurate doses to targets and organs at risk will benefit the individual patients and decrease uncertainties in clinical trials. Imaging can be used to measure activity distribution in vivo, and this information can be used to determine patient-specific treatment plans where the dose to the targets and organs at risk can be calculated. The development and adoption of imaging-based dosimetry methods is particularly beneficial in early clinical trials. In this work we discuss dosimetric accuracy needs in modern radiation oncology, uncertainties in the dosimetry in RPT, and best approaches for imaging and dosimetry of internal radionuclide therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Development of radiopharmaceuticals for targeted alpha therapy: Where do we stand?

Targeted alpha therapy is an oncological treatment, where cytotoxic doses of alpha radiation are locally delivered to tumor cells, while the surrounding healthy tissue is minimally affected. This therapeutic strategy relies on radiopharmaceuticals made of medically relevant radionuclides chelated by ligands, and conjugated to targeting vectors, which promote the drug accumulation in tumor sites. This review discusses the state-of-the-art in the development of radiopharmaceuticals for targeted alpha therapy, breaking down their key structural components, such as radioisotope, targeting vector, and delivery formulation, and analyzing their pros and cons. Moreover, we discuss current drawbacks that are holding back targeted alpha therapy in the clinic, and identify ongoing strategies in field to overcome those issues, including radioisotope encapsulation in nanoformulations to prevent the release of the daughters. Lastly, we critically discuss potential opportunities the field holds, which may contribute to targeted alpha therapy becoming a gold standard treatment in oncology in the future.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Coded aperture and Compton imaging for the development of 225 Ac‐based radiopharmaceuticals

Abstract Background Targeted alpha‐particle therapy (TAT) has great promise as a cancer treatment. Arguably the most promising TAT radionuclide that has been proposed is 225 Ac. The development of 225 Ac‐based radiopharmaceuticals has been hampered due to the lack of effective means to study the daughter redistribution of these agents in small animals at the preclinical stage. Purpose The ability to directly image the daughters, namely 221 Fr and 213 Bi, via their gamma‐ray emissions would be a boon for preclinical studies. That said, conventional medical imaging modalities, including single photon emission computed tomography (SPECT) based on nonmultiplexed collimation, cannot be employed due to sensitivity limitations. Methods As an alternative, we propose the use of both coded aperture and Compton imaging with the former modality suited to the 218‐keV gamma‐ray emission of 221 Fr and the latter suited to the 440‐keV gamma‐ray emission of 213 Bi. Results This work includes coded aperture images of 221 Fr and Compton images of 213 Bi in tumor‐bearing mice injected with 225 Ac‐based radiopharmaceuticals. Conclusions These results are the first demonstration of visualizing and quantifying the 225 Ac daughters in small animals through the application of coded aperture and Compton imaging.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

CD46-Targeted Theranostics for PET and 225 Ac-Radiopharmaceutical Therapy of Multiple Myeloma

Multiple myeloma is a plasma cell malignancy with an unmet clinical need for improved imaging methods and therapeutics. Recently, we identified CD46 as an overexpressed therapeutic target in multiple myeloma and developed the antibody YS5, which targets a cancer-specific epitope on this protein. We further developed the CD46-targeting PET probe [ 89 Zr]Zr-DFO-YS5 for imaging and [ 225 Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of prostate cancer. These prior studies suggested the feasibility of the CD46 antigen as a theranostic target in multiple myeloma. Herein, we validate [ 89 Zr]Zr-DFO-YS5 for immunoPET imaging and [ 225 Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of multiple myeloma in murine models. In vitro saturation binding was performed using the CD46 expressing MM.1S multiple myeloma cell line. ImmunoPET imaging using [ 89 Zr]Zr-DFO-YS5 was performed in immunodeficient (NSG) mice bearing subcutaneous and systemic multiple myeloma xenografts. For radioligand therapy, [ 225 Ac]Ac-DOTA-YS5 was prepared, and both dose escalation and fractionated dose treatment studies were performed in mice bearing MM1.S-Luc systemic xenografts. Tumor burden was analyzed using BLI, and body weight and overall survival were recorded to assess antitumor effect and toxicity. [ 89 Zr]Zr-DFO-YS5 demonstrated high affinity for CD46 expressing MM.1S multiple myeloma cells (K d = 16.3 nmol/L). In vitro assays in multiple myeloma cell lines demonstrated high binding, and bioinformatics analysis of human multiple myeloma samples revealed high CD46 expression. [ 89 Zr]Zr-DFO-YS5 PET/CT specifically detected multiple myeloma lesions in a variety of models, with low uptake in controls, including CD46 knockout (KO) mice or multiple myeloma mice using a nontargeted antibody. In the MM.1S systemic model, localization of uptake on PET imaging correlated well with the luciferase expression from tumor cells. A treatment study using [ 225 Ac]Ac-DOTA-YS5 in the MM.1S systemic model demonstrated a clear tumor volume and survival benefit in the treated groups. Our study showed that the CD46-targeted probe [ 89 Zr]Zr-DFO-YS5 can successfully image CD46-expressing multiple myeloma xenografts in murine models, and [ 225 Ac]Ac-DOTA-YS5 can effectively inhibit the growth of multiple myeloma. These results demonstrate that CD46 is a promising theranostic target for multiple myeloma, with the potential for clinical translation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Production and purification of research scale 161 Tb using cation-exchange semi-preparative HPLC for radiopharmaceutical applications

Terbium-161 ( 161 Tb) is emerging as a promising radionuclide for cancer therapy due to its favorable nuclear properties that are similar to clinically established lutetium-177 ( 177 Lu) along with its therapeutic edge arising from the higher number of Auger and conversion electrons per decay. These low energy electrons result in higher cytotoxicity within a short range of the decaying nuclei to enhance therapeutic efficacy. Despite these promising characteristics, a significant challenge remains in the lack of a domestic 161 Tb supply in the United States, which poses an obstacle to the advancement of 161 Tb-based radiopharmaceutical research and development. Here, this study developed a reliable cation-exchange high-performance liquid chromatography-based method for purification of reactor-produced 161 Tb at quantities suitable to support research and preclinical studies. The purified 161 Tb product showed high radionuclidic purity with excellent radiochemical purity, and the successful labeling studies with the DOTA chelator and DOTA-TATE peptide demonstrated the effective incorporation of the purified 161 Tb into radiopharmaceuticals designed for targeted cancer therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

IAEA Activities on 67Cu, 186Re, 47Sc Theranostic Radionuclides and Radiopharmaceuticals

Despite interesting properties, the use of 67 Cu, 186 Re and 47 Sc theranostic radionuclides inpreclinical studies and clinical trials is curtailed by their limited availability due to a lack of widelyestablished production methods. An IAEA Coordinated Research Project (CRP) was initiated toidentify important technical issues related to the production and quality control of these emergingradionuclides and related radiopharmaceuticals, based on the request from IAEA Member States.The international team worked on targetry, separation, quality control and radiopharmaceutical aspectsof the radionuclides obtained from research reactors and cyclotrons leading to preparation ofa standard recommendations for all Member States. The CRP was initiated in 2016 with fourteenparticipants from thirteen Member States from four continents. Extraordinary results on the production,quality control and preclinical evaluation of selected radionuclides were reported in this projectthat was finalized in 2020. The outcomes, outputs and results of this project achieved by participatingMember States are described in this minireview.

Pharmacology & Pharmacy↗
DOE OSTI2021

A Framework for Patient-Centered Pathways of Care for Radiopharmaceutical Therapy: An ASTRO Consensus Document

Radiopharmaceutical therapy (RPT) is an area of projected growth and importance with several agents in clinical use, new agents in late-phase clinical trials, and many others under testing and development. This article proposes a framework for developing pathways of care that can be broadly applied to all RPTs, representing the current status of RPT. It suggests foundational elements for many pathways of care for patients with cancer and concludes with areas in active development and the future horizon for RPT treatment centers. Developing a framework for patient-centered pathways of care is a critical step in establishing RPT as standard therapy for patients with a diverse spectrum of cancers. This expected increase in RPT treatment options will affect a much larger population of patients with complex cancer. It will also require enhanced coordination and collaboration among appropriately qualified personnel with diverse expertise in image acquisition, image interpretation, quantitative imaging, dosimetry calculation, radiation quality assurance and safety as well as oncology care and RPT-induced sequelae and response assessment. The essential role of this evolving RPT care team within multidisciplinary oncology care is a cornerstone of this framework for a patient-centered pathway of care for RPT. Given the status of current RPT practice and the horizon for future applications, this patient-centered pathway of care guidance is timely and should help inform future clinical RPT practice paradigms. A task force was recruited from the Theranostic Working Group of the American Society for Radiation Oncology (ASTRO) in May 2019 with equal representation from the nuclear medicine community. The task force expanded on a framework that was originally conceived by the Working Group for patient-centered care. This framework was developed to incorporate the strengths of both radiation oncologists and nuclear medicine physicians. The manuscript was then developed by the task force and posted on the ASTRO website for a 6-week public comment period ending in July 2020. Comments were adjudicated, and the draft was sent to external organizations for potential endorsement. This document was sent to the ASTRO Board of Directors in October 2020 for approval.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

[ 89 Zr]Zr-DFO-TOC: a novel radiopharmaceutical for PET imaging of somatostatin receptor positive neuroendocrine tumors

Neuroendocrine tumors (NETs) are clinically diverse types of tumors that can arise anywhere in the body. Previous studies have shown that somatostatin receptors (SSTRs) are overexpressed on NET cell membranes relative to healthy tissue, allowing for tumor targeting through radiolabeled somatostatin analogs (SSAs). This work aims to develop a novel 89 Zr-labeled tracer incorporating the SSA, octreotide (TOC), for positron emission tomography (PET) imaging of SSTR + NETs and predictive dosimetry calculations, leveraging the excellent nuclear (t ½ = 3.27 days, β+ = 22.3%, β + avg = 395.5 keV) and chemical characteristics (+ 4 oxidation state, preferential coordination number of 7/8, favorable aqueous chemistry) of 89 Zr. In combination with 89 Zr, the known radiochemistry with the chelator deferoxamine (DFO) gives reason to believe that this radiopharmaceutical incorporating an octreotide conjugate will be successful in studying the suitability of detecting SSTR + NETs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma

Background: Malignant gliomas are deadly tumours with few therapeutic options. Although immunotherapy may be a promising therapeutic strategy for treating gliomas, a significant barrier is the CD11b + tumour-associated myeloid cells (TAMCs), a heterogeneous glioma infiltrate comprising up to 40% of a glioma's cellular mass that inhibits anti-tumour T-cell function and promotes tumour progression. A theranostic approach uses a single molecule for targeted radiopharmaceutical therapy (TRT) and diagnostic imaging; however, there are few reports of theranostics targeting the tumour microenvironment. Methods: Utilizing a newly developed bifunctional chelator, Lumi804, an anti-CD11b antibody (αCD11b) was readily labelled with either Zr-89 or Lu-177, yielding functional radiolabelled conjugates for PET, SPECT, and TRT. Findings: 89 Zr/ 177 Lu-labeled Lumi804-αCD11b enabled non-invasive imaging of TAMCs in murine gliomas. Additionally, 177 Lu-Lumi804-αCD11b treatment reduced TAMC populations in the spleen and tumour and improved the efficacy of checkpoint immunotherapy. Interpretation: 89 Zr- and 177 Lu-labeled Lumi804-αCD11b may be a promising theranostic pair for monitoring and reducing TAMCs in gliomas to improve immunotherapy responses.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Preclinical studies of a PARP targeted, Meitner-Auger emitting, theranostic radiopharmaceutical for metastatic ovarian cancer

Advanced ovarian cancer currently has few therapeutic options. Poly(ADP-ribose) polymerase (PARP) inhibitors bind to nuclear PARP and trap the protein-inhibitor complex to DNA. This work investigates a theranostic PARP inhibitor for targeted radiopharmaceutical therapy of ovarian cancer in vitro and PET imaging of healthy mice in vivo. Methods: [ 77 Br]RD1 was synthesized and assessed for pharmacokinetics and cytotoxicity in human and murine ovarian cancer cell lines. [ 76 Br]RD1 biodistribution and organ uptake in healthy mice were quantified through longitudinal PET/CT imaging and ex vivo radioactivity measurements. Organ-level dosimetry following [ 76/77 Br]RD1 administration was calculated using RAPID, an in-house platform for absorbed dose in mice, and OLINDA for equivalent and effective dose in human. Results: The maximum specific binding (B max ), equilibrium dissociation constant (K d ), and nonspecific binding slope (NS) were calculated for each cell line. These values were used to calculate the cell specific activity uptake for cell viability studies. The half maximal effective concentration (EC 50 ) was measured as 0.17 (95 % CI: 0.13–0.24) nM and 0.46 (0.13–0.24) nM for PARP(+) and PARP(–) expressing cell lines, respectively. The EC 50 was 0.27 (0.21–0.36) nM and 0.30 (0.22–0.41) nM for BRCA1(–) and BRCA1(+) expressing cell lines, respectively. When measuring the EC 50 as a function of cellular activity uptake and nuclear dose, the EC 50 ranges from 0.020 to 0.039 Bq/cell and 3.3–9.2 Gy, respectively. Excretion through the hepatobiliary and renal pathways were observed in mice, with liver uptake of 2.3 ± 0.4 %ID/g after 48 h, contributing to estimated absorbed dose values in mice of 19.3 ± 0.3 mGy/MBq and 290 ± 10 mGy/MBq for [ 77 Br]RD1 and [ 76 Br]RD1, respectively. Conclusion: [ 77 Br]RD1 cytotoxicity was dependent on PARP expression and independent of BRCA1 status. Finally, the in vitro results suggest that [ 77 Br]RD1 cytotoxicity is driven by the targeted Meitner-Auger electron (MAe) radiotherapeutic effect of the agent. Further studies investigating the theranostic potential, organ dose, and tumor uptake of [ 76/77 Br]RD1 are warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Diagnostic, Prognostic, and Therapeutic Use of Radiopharmaceuticals in the Context of SARS-CoV-2

The coronavirus disease 2019 (COVID-19) outbreak has devastated the healthcare systems and economies of over 200 countries in just a few months. The etiological agent of COVID-19, SARS-CoV-2, is a highly contagious virus that can be transmitted by asymptomatic and symptomatic carriers alike. While in vitro testing techniques have allowed for population-wide screening, prognostic tools are required to assess the disease severity and therapeutic response, contributing to improve the patient clinical outcomes. Moreover, no specific antiviral against COVID-19 exists at the time of publication, severely limiting treatment against the infection. Hence, there is an urgent clinical need for innovative therapeutic strategies that may contribute to manage the COVID-19 outbreak and prevent future pandemics. In this work, we critically examine recent diagnostic, prognostic, and therapeutic advancements for COVID-19 in the field of radiopharmaceuticals. First, we summarize the gold standard techniques used to diagnose COVID-19, including in vitro assays and imaging techniques, and then discuss how radionuclide-based nuclear imaging provides complementary information for prognosis and treatment management of infected patients. Second, we introduce new emerging types of radiotherapies that employ radioimmunoconjugates, which have shown selective cytotoxic response in oncological studies, and critically analyze how these compounds could be used as therapeutic agents against SARS-CoV-2. Finally, this Perspective further discusses the emerging applications of radionuclides to study the behavior of pulmonary SARS-CoV-2 aerosol particles.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

[18F]Tosyl fluoride as a versatile [18F]fluoride source for the preparation of 18F-labeled radiopharmaceuticals

Abstract Positron emission tomography (PET) is an in vivo imaging technology that utilizes positron-emitting radioisotope-labeled compounds as PET radiotracers that are commonly used in clinic and in various research areas, including oncology, cardiology, and neurology. Fluorine-18 is the most widely used PET-radionuclide and commonly produced by proton bombardment of 18 O-enriched water in a cyclotron. The [ 18 F]fluoride thus obtained generally requires processing by azeotropic drying in order to completely remove H 2 O before it can be used for nucleophilic radiofluorination. In general, the drying step is important in facilitating the radiofluorination reactions and the preparation of 18 F-labeled PET radiotracers. In this communication, we have demonstrated the feasibility of using [ 18 F]tosyl fluoride ([ 18 F]TsF) as a versatile [ 18 F]fluoride source for radiofluorination to bypass the azeotropic drying step, and we have developed a continuous flow solid-phase radiosynthesis strategy to generate [ 18 F]TsF in a form that is excellent for radiofluorination. [ 18 F]TsF shows high reactivity in radiofluorination and provides the features suitable for preparing PET radiotracers on a small scale and exploring novel radiolabeling technologies. Thus, using [ 18 F]TsF as a [ 18 F]fluoride source is a promising strategy that facilitates radiofluorination and provides a convenient and efficient solution for the preparation of 18 F-labeled radiopharmaceuticals that is well matched to the emerging trends in PET imaging technologies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

Synthesis of fluorinated radiopharmaceuticals via electrochemical fluorination

Provided herein are methods and compositions for the electrochemical selective radiofluorination of aromatic molecules. The resulting fluorine-18 labeled compounds are ideal radionuclides for use in Positron Emission Tomography (PET); they are also difficult to radiolabel efficiently and with high specific activity using existing approaches. For example, radiopharmaceuticals such as [F18]L-DOPA, which is indispensable in PET brain disease imaging, may be made electrochemically with high radiochemical yield and high specific activity using 18F-. The invention process described herein opens new possibilities and provides wider access to PET tracers such as 18F-L-Dopa, since 18F- is much more widely available than the 18F2, currently used for synthesis of electron rich substrates.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗