A Cu-64/Cu-67 Bombesin ligand as a theranostic for cancer

1237 Background: The gastrin releasing peptide receptor (GRPR) is a promising target for imaging and targeted radionuclide therapy for a variety of cancers including glioma, breast cancer and prostate cancer. Positron-emitting copper-64 has attractive physical characteristics for imaging and provides a diagnostic partner for the therapeutic radionuclide copper-67. A sarcophagine-based macrobicyclic cage amine conjugated to a bombesin (BBN) analogue was prepared. The complex was radiolabelled with [64Cu]CuII or [67Cu]CuII and the tumor targeting and therapeutic efficacy was evaluated in a PC-3 xenograft prostate cancer mouse model. The dosimetry of the [67Cu]Cu(SAR-BBN) complex was evaluated in healthy mice. Methods: A sarcophagine ligand containing a PEG-linker and a GRPR antagonist (SAR-BBN) was radiolabelled with [64Cu]CuII or [67Cu]CuII at either room temperature or 40°C in Results: [64Cu]Cu(SAR-BBN) displayed excellent tumour uptake and significant tumor retention at 24 hours post-injection Biodistribution studies showed rapid clearance through the kidneys, as well as hepatobiliary clearance. Uptake was also seen in the pancreas, an organ which expresses GRPR. Therapy with [67Cu]Cu(SAR-BBN) in the PC-3 prostate cancer model showed that it was well tolerated with no toxicity observed as assessed by body weight changes. [67Cu]Cu(SAR-BBN) significantly inhibited tumor growth, with a tumor growth inhibition of 93.5% on day 22, the last day all mice remained in the study. [67Cu]Cu(SAR-BBN) significantly increase survival (p