Melanoma targeting with [ 99m Tc(N)(PNP3)]-labeled α-melanocyte stimulating hormone peptide analogs: Effects of cyclization on the radiopharmaceutical properties

Synthesis, Characterization, and Initial Biological Evaluation of [99mTc]Tc‐Tricarbonyl‐labeled DPA‐α‐MSH Peptide Derivatives for Potential Melanoma Imaging

“…Notably, the insertion of linkers between the chelator and the amino acid sequence did not affect the stability of our compounds. These data are in perfect agreement with our previous studies, on the corresponding [ 64 Cu][Cu]‐NOTA‐ and [ 99m Tc][Tc(N)(PNP3)]‐labeled NAP‐NS1–peptides …”

“…[ 99m Tc]Tc‐ 3 displayed less hydrophilic character than [ 99m Tc]Tc‐ 1 and [ 99m Tc]Tc‐ 2 , implying that the linkers increased the hydrophilicity. Still, the hydrophilicity was somewhat lower than for [ 64 Cu]Cu‐NOTA‐ and [ 99m Tc][Tc(N)(PNP3)]‐NAPamide analogues in earlier studies, likely due to the lipophilic tendency of the carbonyl groups. Moreover, cyclic α‐MSH analogues showed higher hydrophilicity than linear peptides .…”

“…The stabilities of [ 99m Tc]Tc‐ 1 , [ 99m Tc]Tc‐ 2 or [ 99m Tc]Tc‐ 3 were determined with HPLC monitoring the variation of the radiochemical purity of the compounds after incubation in PBS and human serum for 1 h and 24 h. The compounds remained stable in the reaction solutions (>97 % after 24 h; Table ). In previous studies, on the corresponding 64 Cu‐labeled NOTA‐ and [ 99m Tc]Tc(N)(PNP3)]‐labeled NAP‐NS–peptides also showed high stability in PBS and serum, with over 97 % intact complex in the supernatant …”

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

“…It should be noted, however, that the cyclic peptide had a different C-terminus and a higher molecular weight than the linear peptide. A more informative comparison was reported by Carta et al [108] who synthesized linear H-Cys-Ahx-β-Ala-[Lys 4 ,D-Phe 7 ,Glu 10 ,Arg 11 ]-α-MSH [4][5][6][7][8][9][10][11][12][13] and the corresponding (4−10) lactam-cyclized Cys-Ahx-β-Ala-cyclo[Lys 4 ,D-Phe 7 ,Glu 10 ,Arg 11 ]-α-MSH [4][5][6][7][8][9][10][11][12][13] . Radiolabeling was done as outlined above by formation of a stable radiometal complex {[ 99m Tc(N)](Cys-Ahx-β-Ala)}-peptide using PNP3.…”

“…The former chelator yielded superior biodistribution results than the latter. Incorporation of 99m Tc(N)](Cys-Ahx-β-Ala)} containing cyclic MSH [4][5][6][7][8][9][10][11][12][13] analog [108]. The stability of the latter radiopeptide complex in vivo was judged good; however non-specific tissue uptake of 99m Tc was relatively high and thus the potential of the peptide limited.…”