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Background: Poly (ADP-ribose) polymerase (PARP) enzymes are crucial for the repair of DNA single-strand breaks and have become key therapeutic targets in homologous recombination-deficient cancers, including prostate cancer. To enable non-invasive monitoring of PARP-1 expression, several PARP-1-targeting positron emission tomography (PET) tracers have been developed. Here, we aimed to preclinically investigate [carbonyl-11C]DPQ as an alternative PARP-1 PET tracer as it features a strongly distinct chemotype compared to the frontrunners [18F]FluorThanatrace and [18F]PARPi. Results: [carbonyl-11C]DPQ was synthesised in a GE TracerLab FXC2 module, yielding sufficient activity (940 ± 410 MBq), molar activity (53 ± 16 GBq/µmol) and radiochemical purity (> 97%) for subsequent preclinical evaluation. [carbonyl-11C]DPQ showed high stability in formulation, in human plasma, and when incubated with human liver microsomes. In vitro, similar specific uptake was observed in both PC3 prostate cancer cells and CHO-K1 Chinese hamster ovary cells. However, in vivo studies using fertilised chicken eggs (in ovo model) revealed poor and non-displaceable tumour accumulation in PC3-derived xenografts, despite confirmed vascularisation and PARP-1 expression. Rapid uptake was observed in the liver (10 min), with less than 30% of the intact compound remaining in the liver 70 min post-injection. Conclusions: Although [carbonyl-11C]DPQ demonstrated metabolic stability and specific binding in vitro, suboptimal tumour-targeting properties and pronounced liver metabolism were observed in ovo. Therefore, further animal experiments with mammalian models were not indicated. [ABSTRACT FROM AUTHOR]

[177Lu]Lu-PSMAI&T is widely used for the radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC). Since this kind of therapy has gained a large momentum in recent years, an upscaled production process yielding multiple patient doses in one batch has been developed. During upscaling, the established production method as well as the HPLC quality control were challenged. A major finding was a correlation between the specific activity and the formation of a pre-peak, presumably caused by radiolysis. Hence, nonradioactive reference standards were irradiated with an X-ray source and the formed pre-peak was subsequently identified as a deiodination product by UPLC-MS. To confirm the occurrence of the same deiodinated side product in the routine batch, a customized deiodinated precursor was radiolabeled and analyzed with the same HPLC setup, revealing an identical retention time to the pre-peak in the formerly synthesized routine batches. Additionally, further cyclization products of [177Lu]Lu-PSMAI&T were identified as major contributors to radiochemical impurities. The comparison of two HPLC methods showed the likelihood of the overestimation of the radiochemical purity during the synthesis of [177Lu]Lu-PSMAI&T. Finally, a prospective cost reduction through an optimization of the production process was shown. [ABSTRACT FROM AUTHOR]