Matched pair imaging for peptide targeted melanoma alpha-particle therapy

Objectives The goal of the study was to develop and validate the peptide Pb-203-DOTA-Re(Arg11)CCMSH as a matched pair imaging agent for the α-particle emitting Pb-212-DOTA-Re(Arg11)CCMSH melanoma therapeutic. A matched-pair imaging agent is critical for determining tumor uptake, patient specific dosimetry and the proper therapeutic dose administration.

Methods DOTA-Re(Arg11)CCMSH was labeled with the γ-emitting radionuclide Pb-203 in 0.5 M NH4OAc (pH 5.4) at 85°C for 30 min, followed by HPLC purification. The pharmacokinetics and SPECT imaging properties of Pb-203-DOTA-Re(Arg11)CCMSH were examined in B16/F1 melanoma bearing mice.

Results Pb-203 and Pb-212 labeled DOTA-Re(Arg11)CCMSH displayed receptor-mediated tumor uptake of 11.25±1.52%ID/g and 11.87±3.24 %ID/g at 2 h post-injection (pi). Except for the kidneys, non-target organ uptakes were low (< 1 %ID/g) at 2, 4 and 24 h pi. The renal uptake for the Pb-203 and Pb-212 labeled peptides was 7.78±1.42 %ID/g and 7.31±1.26 %ID/g at 2 h pi. Both peptides exhibited rapid clearance, with ~89% of the radioactivity in the urine 2 h pi. Melanoma lesions were visualized with Pb-203-DOTA-Re(Arg11)CCMSH via SPECT imaging 2 h pi.

Conclusions Pb-203-DOTA-Re(Arg11)CCMSH displayed nearly identical tumor uptake values and clearance kinetics as the Pb-212 therapeutic agent. Moreover, Pb-203-DOTA-Re(Arg11)CCMSH was able to detect melanoma tumors using SPECT imaging, demonstrating its utility as a matched pair imaging agent to support targeted α-particle therapy.

Research Support NIH R42CA85106, R44CA114920