RT Journal Article SR Electronic T1 Development of a new bifunctional PSMA ligand as a theranostic for prostate cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1057 OP 1057 VO 60 IS supplement 1 A1 Zia, Nicholas A1 Cullinane, Carleen A1 Van Zuylekom, Jessica A1 Haskali, Mohammad A1 Roselt, Peter A1 van Dam, Ellen A1 Harris, Matthew A1 Hicks, Rodney A1 Donnelly, Paul YR 2019 UL http://jnm.snmjournals.org/content/60/supplement_1/1057.abstract AB 1057Background: The prostate-specific membrane antigen (PSMA) is a promising target for imaging and targeted radionuclide therapy of metastatic prostate cancer. Positron-emitting copper-64 has attractive physical characteristics for imaging and provides a diagnostic partner for the therapeutic radionuclide copper-67. New sarcophagine-based macrobicyclic cage amine ligands were prepared conjugated to either one or two glutamate-urea-lysine containing inhibitors of PSMA. The new complexes were radiolabelled with [64Cu]CuII and evaluated in a LNCaP xenograft prostate cancer mouse model. Methods: A sarcophagine ligand with a single glutamate-urea-lysine functional group (SarPSMA) was prepared as well as derivative containing two glutamate-urea-lysine functional groups (SarbisPSMA). Both ligands could be radiolabelled with [64Cu]CuII at room temperature in <20 min to give complexes with high radiochemical purity. Small animal PET/CT images and organ biodistribution data of LNCaP tumour-bearing NGS mice were acquired at 1, 4, and 24 hr post-injection following intravenous administration of either [64Cu]Cu(SarPSMA) or [64Cu]Cu(SarbisPSMA). Results: Tumour uptake of [64Cu]Cu(SarPSMA) peaked at 1 hr to 9% IA/g but tumour retention was low with 1% IA/g remaining at 24 hrs post-injection and rapid renal clearance. In comparison, [64Cu]Cu(SarbisPSMA) displayed significantly increased tumour uptake and retention (13% IA/g at 24 h post injection. Tumour as well as kidney uptake could be blocked by injection of excess non-radioactive peptide. Conclusions: [64Cu]Cu(SarbisPSMA) has superior tumour uptake and retention when compared to monomeric [64Cu]Cu(SarPSMA) and warrants further investigation.