Evaluation of Tricine and EDDA as Co-ligands for ^99mTc-Labeled HYNIC-MSH Analogs for Melanoma Imaging

Title:Evaluation of Tricine and EDDA as Co-ligands for ^99mTc-Labeled HYNIC-MSH Analogs for Melanoma Imaging

Volume: 15 Issue: 1

Author(s): Maria Fernanda Garcia, Xiuli Zhang, Fabio Gallazzi, Marcelo Fernandez, Maria Moreno, Juan Pablo Gambini, Williams Porcal, Pablo Cabral and Thomas P. Quinn

Affiliation:

Keywords: HYNIC, melanoma imaging, MSH analogs, ^99mTc.

Abstract: 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.

Cite this article as:

Fernanda Garcia Maria, Zhang Xiuli, Gallazzi Fabio, Fernandez Marcelo, Moreno Maria, Gambini Juan Pablo, Porcal Williams, Cabral Pablo and P. Quinn Thomas, Evaluation of Tricine and EDDA as Co-ligands for ^99mTc-Labeled HYNIC-MSH Analogs for Melanoma Imaging, Anti-Cancer Agents in Medicinal Chemistry 2015; 15 (1) . https://dx.doi.org/10.2174/1871520614666140825123150