Background: Lactam cyclized alpha-melanocyte stimulating hormone (α-MSH) analogues exhibit
high stability and affinity for the MC1-R receptors over expressed in melanoma cells. Recently, we reported a
novel 99mTc-HYNIC-cycMSH4-13 analogue with the HYNIC chelator directly attached to the lactam cyclized ring.
Objective: In this study we proposed the introduction of a 6-aminohexanoic acid (Ahx) linker between the
HYNIC chelator and lactam cyclized peptide cycMSH4-13
to reduce steric hindrance and improve the melanoma
targeting and imaging proprieties of the radiolabeled peptide.
peptide was synthesized on an automated peptide synthesizer and displayed
of 0.3 nM using B16/F1 cells. The 99m
Tc/tricine radiolabeled peptide was examined for radiochemical
purity, stability and cell binding. In vivo, biodistribution and planar gamma imaging studies were performed in
B16/F1 melanoma tumor bearing C57BK mice.
was obtained with a radiochemical purity >95%, was stable up to 24 h at
room temperature and exhibited high binding and rapid internalization in B16/F1 cells. In vivo biodistribution
studies showed a tumor uptake of 4.92 ± 0.92 % ID/g and 2.78 ± 1.48 % ID/g at 2 h and 4 h post injection,
respectively. Whole-body clearance was rapid through urinary excretion. The melanoma tumors were clearly
visualized by planar gamma imaging.
was shown radiochemically stability and exhibited rapid and
selective uptake in melanoma cells and tumors. Imaging studies yielded promising preclinical results, warranting
further evaluation of 99m
Tc-HYNIC-cycMSH analogs as melanoma specific imaging agents.