Evaluation of tricine and EDDA as Co-ligands for 99mTc-labeled HYNIC-MSH analogs for melanoma imaging

RADIOQUIMICA

MELANOMA

TECNECIO

BIBLIOGRAFIA NACIONAL QUIMICA

2015

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. - See more at: http://www.eurekaselect.com/124097/article#sthash.esh9JhlX.dpuf

Anti-Cancer Agents in Medicinal Chemistry v.15, no. 1, 2015. -- p. 122-130

Bentham Science

2015

PDF

Inglés

Artículo

ISSN: 1875-5992 (En línea)

ISSN: 1871-5206 (Impreso)

PDF