Matrix Metalloproteinase 9 Targeting Peptides: Syntheses, 68Ga-labeling, and Preliminary Evaluation in a Rat Melanoma Xenograft Model

Biopanning of tumor cells was used in order to identify matrix metalloproteinase 9 (MMP-9) targeting peptides. The tumor cell targeting peptide (TCTP-1) and two modified versions thereof were evaluated as imaging agents for positron emission tomography (PET) using a rat melanoma xenograft model. For the PET imaging purposes, the 3 peptides were 1,4,7,10-tetraazacyclo-dodecane-N′,N′′,N′′′,N′′′′-tetraacetic acid (DOTA) conjugated and labeled with Gallium-68 (68Ga) and preliminarily evaluated: (1) cyclic 68Ga-DOTA-TCTP-1 with cystine bridge, (2) cyclic 68Ga-DOTA-lactam-TCTP-1 with a lactam bridge, and (3) linear 68Ga-DOTA-lin-TCTP-1. The whole-body distribution kinetics and tumor targeting of the intravenously administered 68Ga-DOTA-peptides were evaluated in vivo by PET and ex vivo by measuring the radioactivity of excised tissues. In addition, the in vivo stability of the radiolabeled peptides in rat plasma, tumor tissue, and urine was studied. All 68Ga-DOTA-peptides were cleared via the liver and kidneys,...