Abstract
The purpose of this study was to evaluate the effect of linkers on tumor targeting and biodistribution of [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) {[(99m)Tc]Tc(CO)(3)-1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid-polyethylene glycol-Nle-c[Asp-His-d-Phe-Arg-Trp-Lys]-CONH(2)} and [(99m)Tc]Tc(CO)(3)-NOTA-AocNle-CycMSH(hex) {[(99m)Tc]Tc(CO)(3)-NOTA-8-aminooctanoic acid-Nle-CycMSH(hex)} on B16/F10 melanoma-bearing mice. NOTA-PEG(2)Nle-CycMSH(hex) and NOTA-AocNle-CycMSH(hex) were synthesized and radiolabeled with [(99m)Tc]Tc via the {[(99m)Tc]Tc(CO)(3)(OH(2))(3)}(+) intermediate. The biodistribution of [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) and [(99m)Tc]Tc(CO)(3)-NOTA-AocNle-CycMSH(hex) was determined on B16/F10 melanoma-bearing C57 mice. The melanoma imaging property of [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) was determined on B16/F10 melanoma-bearing C57 mice. [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) and [(99m)Tc]Tc(CO)(3)-NOTA-AocNle-CycMSH(hex) were readily prepared with more than 90% radiochemical yields and exhibited MC1R-specific binding on B16/F10 melanoma cells. [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) exhibited a higher tumor uptake than [(99m)Tc]Tc(CO)(3)-NOTA-AocNle-CycMSH(hex) at 2, 4, and 24 h postinjection. The tumor uptake of [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) was 13.63 ± 1.13, 31.93 ± 2.57, 20.31 ± 3.23, and 1.33 ± 0.15% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. The tumor uptake of [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) was 1.6 and 3.4 times the tumor uptake of [(99m)Tc]Tc(CO)(3)-NOTA-AocNle-CycMSH(hex) at 2 and 4 h postinjection, respectively. Meanwhile, the normal organ uptake of [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) was lower than 1.8% ID/g at 2 h postinjection. The renal uptake of [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) was only 1.73 ± 0.37, 0.73 ± 0.14, and 0.03 ± 0.01% ID/g at 2, 4, and 24 h postinjection, respectively. [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) showed high tumor to normal organ uptake ratios at 2 h postinjection. Single-photon emission computed tomography imaging revealed that the B16/F10 melanoma lesions could be clearly visualized by [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) at 2 h postinjection. Overall, the high tumor uptake and low kidney uptake of [(99m)Tc]Tc(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) highlighted its potential for melanoma imaging and warranted the future evaluation of [(188)Re]Re(CO)(3)-NOTA-PEG(2)Nle-CycMSH(hex) for melanoma therapy.