Correlation between molar activity, injection mass and uptake of the PARP targeting radiotracer [F-18]olaparib in mouse models of glioma

Purpose Radiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inhibitors for diagnostic and radionuclide therapeutic applications. Here, we performed a systematic evaluation by varying the molar activity of [F-18]olaparib and the injected mass of [F-Total]olaparib to investigate the effects on tumour and normal tissue uptake in two subcutaneous human glioblastoma xenograft models. Methods [F-18]Olaparib uptake was evaluated in the human glioblastoma models: in vitro on U251MG and U87MG cell lines, and in vivo on tumour xenograft-bearing mice, after administration of [F-Total]olaparib (varying injected mass: 0.04-8.0 mu g, and molar activity: 1-320 GBq/mu mol). Results Selective uptake of [F-18]olaparib was demonstrated in both models. Tumour uptake was found to be dependent on the injected mass of [F-Total]olaparib (mu g) but not the molar activity. An injected mass of 1 mu g resulted in the highest tumour uptake (up to 6.9 +/- 1.3%ID/g), independent of the molar activity. In comparison, both the lower and higher injected masses of [F-Total]olaparib resulted in lower relative tumour uptake (%ID/g; P 0.5 mu g). Conclusion Our findings show that the injected mass of [F-Total]olaparib has significant effects on tumour uptake. Moderate injected masses of PARP inhibitor-derived radiopharmaceuticals may lead to improved relative tumour uptake and tumour-to-background ratio for cancer diagnosis and radionuclide therapy

Radiosynthesis of [18F]ArylSCF2H using aryl boronic acids, S-(chlorofluoromethyl)benzenesulfonothioate and [18F]fluoride

Herein, we report a mild and practical protocol for the copper-catalyzed chlorofluoromethylthiolation of (hetero)aryl boronic acids with the novel reagent PhSO2SCFClH. The resulting products are amenable to halogen exchange 18F-fluorination with cyclotron-produced [18F]fluoride affording [18F]ArSCF2H. This process highlights the combined value of reagent development and (hetero)aryl boron precursors for radiochemistry by adding the [18F]SCF2H group to the list of 18F-motifs within reach for positron emission tomography studies

Additional file 1 of Correlation between molar activity, injection mass and uptake of the PARP targeting radiotracer [18F]olaparib in mouse models of glioma

Additional file 1. Supplementary information