68Ga-Labeling: Laying the Foundation for an Anti-Radiolytic Formulation for NOTA-sdAb PET Tracers

Baudhuin, Henri; Cousaert, Julie; Vanwolleghem, Philippe; Raes, Geert; Caveliers, Vicky; Keyaerts, Marleen; Lahoutte, Tony; Xavier, Catarina

doi:10.3390/ph14050448

Cited by 4 publications

(2 citation statements)

References 42 publications

(53 reference statements)

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“…When applying high radioactive amounts, radiolysis can likely occur. This is due to direct radiation damage emanating from the direct ionization of the surrounding molecules by the emitted radiation [ 76 ]. More specifically, therapeutic radionuclides have an increased propensity to cause radiolysis since they have different emission properties, and higher dosages are often used compared to diagnostic radionuclides and thus may cause more damage to the vector.…”

Section: Bioconjugation Strategiesmentioning

confidence: 99%

Optimizing the Safety and Efficacy of Bio-Radiopharmaceuticals for Cancer Therapy

et al. 2023

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The precise delivery of cytotoxic radiation to cancer cells through the combination of a specific targeting vector with a radionuclide for targeted radionuclide therapy (TRT) has proven valuable for cancer care. TRT is increasingly being considered a relevant treatment method in fighting micro-metastases in the case of relapsed and disseminated disease. While antibodies were the first vectors applied in TRT, increasing research data has cited antibody fragments and peptides with superior properties and thus a growing interest in application. As further studies are completed and the need for novel radiopharmaceuticals nurtures, rigorous considerations in the design, laboratory analysis, pre-clinical evaluation, and clinical translation must be considered to ensure improved safety and effectiveness. Here, we assess the status and recent development of biological-based radiopharmaceuticals, with a focus on peptides and antibody fragments. Challenges in radiopharmaceutical design range from target selection, vector design, choice of radionuclides and associated radiochemistry. Dosimetry estimation, and the assessment of mechanisms to increase tumor uptake while reducing off-target exposure are discussed.

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Section: Bioconjugation Strategiesmentioning

confidence: 99%

Optimizing the Safety and Efficacy of Bio-Radiopharmaceuticals for Cancer Therapy

et al. 2023

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“…However, there are also certain challenges involved in scaling-up radiosynthesis. Decomposition of the reformulated product due to radiolysis, which is more likely at high starting activity, is the major concern; this occurrence is caused by the formation of highly reactive species (hydroxyl radicals, aqueous electron, and superoxide) from water, and can be mitigated by adding anti-oxidants; for instance, radiolysis of [ 68 Ga]-NOTA-sdAb was prevented for up to 3 hours with the combination of 20% ethanol and 5 mg ascorbic acid [ 109 ]. Occurrence of radiolysis of the final product experienced during the scale-up phase have been previously reported.…”

Section: Considerations For Clinical Manufacturingmentioning

confidence: 99%

DNA Repair Enzyme Poly(ADP-Ribose) Polymerase 1/2 (PARP1/2)-Targeted Nuclear Imaging and Radiotherapy

Nguyen

Pacelli

Nader

et al. 2022

Cancers

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Since it was discovered that many tumor types are vulnerable to inhibition of the DNA repair machinery, research towards efficient and selective inhibitors has accelerated. Amongst other enzymes, poly(ADP-ribose)-polymerase 1 (PARP1) was identified as a key player in this process, which resulted in the development of selective PARP inhibitors (PARPi) as anti-cancer drugs. Most small molecule PARPi’s exhibit high affinity for both PARP1 and PARP2. PARPi are under clinical investigation for mono- and combination therapy in several cancer types and five PARPi are now clinically approved. In parallel, radiolabeled PARPi have emerged for non-invasive imaging of PARP1 expression. PARP imaging agents have been suggested as companion diagnostics, patient selection, and treatment monitoring tools to improve the outcome of PARPi therapy, but also as stand-alone diagnostics. We give a comprehensive overview over the preclinical development of PARP imaging agents, which are mostly based on the PARPi olaparib, rucaparib, and recently also talazoparib. We also report on the current status of clinical translation, which involves a growing number of early phase trials. Additionally, this work provides an insight into promising approaches of PARP-targeted radiotherapy based on Auger and α-emitting isotopes. Furthermore, the review covers synthetic strategies for PARP-targeted imaging and therapy agents that are compatible with large scale production and clinical translation.

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Evaluation of the Applicability of External X-ray Radiation to Stimulate the Autoradiolysis Processes in Therapeutic Radiopharmaceuticals (Exemplified by [153Sm]Sm-PSMA-617 and [177Lu]Lu-PSMA-617)

et al. 2023

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68Ga-Labeling: Laying the Foundation for an Anti-Radiolytic Formulation for NOTA-sdAb PET Tracers

Cited by 4 publications

References 42 publications

Optimizing the Safety and Efficacy of Bio-Radiopharmaceuticals for Cancer Therapy

Optimizing the Safety and Efficacy of Bio-Radiopharmaceuticals for Cancer Therapy

DNA Repair Enzyme Poly(ADP-Ribose) Polymerase 1/2 (PARP1/2)-Targeted Nuclear Imaging and Radiotherapy

Evaluation of the Applicability of External X-ray Radiation to Stimulate the Autoradiolysis Processes in Therapeutic Radiopharmaceuticals (Exemplified by [153Sm]Sm-PSMA-617 and [177Lu]Lu-PSMA-617)

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