[99mTc(CO)3]+ and [99mTcO2]+ Radiolabeled Cyclic Melanotropin Peptides for Melanoma SPECT Imaging

The melanoma targeting peptides (Ala-triazol)Ac-Re(Arg11)CCMSH and N4-CO-Re(Arg11)CCMSH were radiolabeled with [99mTc(CO)3]+ and [99mTcO2]+, respectively, and examined for in vitro cell binding, in vivo biodistribution and imaging properties. The (Ala-triazol)Ac-Re(Arg11)CCMSH and N4-CO-Re(Arg11)CCMSH were synthesized as protected peptides on resin followed by rhenium cyclization with [(C6H5)3P]2ReOCl3 in DMF. The peptides were labeled with 99mTc and examined for radiochemical stability and melanoma cell binding. In vivo biodistribution and SPECT/CT imaging studies were performed in B16/F1 melanoma tumor bearing C57 mice. 99mTc(CO)3-(Ala-Triazol)Ac- Re(Arg11)CCMSH and 99mTcO2-N4-CO-Re(Arg11)CCMSH were stable and internalized in B16/F1 melanoma cells upon binding. In vivo biodistribution studies revealed that tumor uptake of 99mTc(CO)3-(Ala-Triazol)Ac-Re(Arg11)CCMSH was 6.08±1.06% ID/g and 7.05±1.48% ID/g at 2 h and 4 h post injection, respectively. Tumor uptake of 99mTcO2-N4-CORe(Arg11)CCMSH was 7.54±1.82% ID/g and 2.28±0.22% ID/g at 1 h and 2 h post injection, respectively. SPECT/CT imaging studies showed that tumor selective uptake of the radiolabeled peptides, which was confirmed by competitive blocking studies.