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

Abstract

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, ⁶⁴Cu [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 ⁶⁴Cu-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 ⁶⁴Cu produced in research reactor toward skeletal imaging by PET. An optimized protocol for the radiolabeling of ⁶⁴Cu (~ 150 MBq) with the BPAMD in high radiochemical purity (> 95%) and excellent in vitro stability was achieved. Comparative hydroxyapatite binding affinity analysis showed that [⁶⁴Cu]Cu-BPAMD demonstrated significantly higher affinity compared to the [⁶⁴Cu]Cu-complex of corresponding polyaza macrocyclic ligand DOTMP (1,4,7,10-tetraazacyclododecane-1',4',7',10'-tetramethylenephosphic acid). In vivo evaluation of [⁶⁴Cu]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 ⁶⁴Cu presents a cost-effective, cyclotron independent alternative to ⁶⁸Ga/¹⁸F based PET agents for detection of skeletal lesions.