Preparation and evaluation of [64Cu]Cu-labeled bisphosphonate amide of DOTA using reactor-produced 64Cu as an affordable skeletal PET imaging agent

Non-invasive imaging of skeletal metastases by Positron Emission Tomography (PET) for cancer prognosis, staging and treatment monitoring is one of the prominent fields of radiopharmaceutical research. Among the radionuclides suitable for PET imaging, 64 Cu [T 1/2 = 12.7 h., EC = 45%, β − =37.1%, β + =17.9%, E β+ (max) = 0.65 MeV] is a versatile candidate due to its attractive decay properties. In the present article, we have investigated the potential of 64 Cu-labeled 4-{[(bis (phosphonomethyl)) carbamoyl] methyl}-7,10-bis (carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (BPAMD), prepared using low specific activity 64 Cu produced in research reactor toward skeletal imaging by PET. An optimized protocol for the radiolabeling of 64 Cu (~ 150 MBq) with the BPAMD in high radiochemical purity (> 95%) and excellent in vitro stability was achieved. Comparative hydroxyapatite binding affinity analysis showed that [ 64 Cu]Cu-BPAMD demonstrated significantly higher affinity compared to the [ 64 Cu]Cu-complex of corresponding polyaza macrocyclic ligand DOTMP (1,4,7,10-tetraazacyclododecane-1′,4′,7′,10′-tetramethylenephosphic acid). In vivo evaluation of [ 64 Cu]Cu-BPAMD in healthy Wistar rats showed selective bone uptake with good contrast and rapid clearance from non-target organs. Overall, the approach of using low specific activity reactor produced 64 Cu presents a cost-effective, cyclotron independent alternative to 68 Ga/ 18 F based PET agents for detection of skeletal lesions.