Evaluation of Tricine and EDDA as Co-ligands for 99mTc-Labeled HYNIC-MSH Analogs for Melanoma Imaging
Maria Fernanda Garcia,
Juan Pablo Gambini,
Thomas P. Quinn.
Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target
melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized
α-MSH analog was labeled with 99m via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma
tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by
the lactam cyclization, resulting in the HYNIC-cyc-MSH analog. The lactam cyclized peptide displayed high affinity and specificity for
MC1-receptors present on B16/F1 melanoma tumor cells, exhibiting an IC50 of 6.48 nM. HYNIC-cyc-MSH was radiolabeled with 99mTc
using two common co-ligands, tricine and EDDA. In vitro, the radiochemical stability, cell binding and efflux properties were similar
between the peptides radiolabeled with tricine and EDDA as co-ligands. In vivo, biodistribution studies (n=4) demonstrated that 99mTc-
HYNIC-cyc-MSH/tricine had superior tumor to muscle and tumor to blood ratios than 99mTc-HYNIC-cyc-MSH/EDDA at early time
points. Planar gamma imaging of melanoma bearing mice showed that 99mTc-HYNIC-cyc-MSH/tricine was able to clearly visualize
tumors, underscoring the potential utility of 99mTc labeled lactam cyclized MSH molecules as melanoma imaging agents.
Keywords: HYNIC, melanoma imaging, MSH analogs, 99mTc.
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