Tc-99m-HYNIC-[Tyr(3)]-octreotide for imaging somatostatin-receptor-positive tumors: Preclinical evaluation and comparison with In-111-octreotide

In this paper we describe the preclinical evaluation of Tc-99m-hydrazinonic otinyl-Tyr(3)-octreotide (HYNIC-TOC) using different coligands for radiolab eling and a comparison of their in vitro and in vivo properties with In-111 -diethylenetriaminepentaacetic acid (DTPA)-octreotide. Methods: HYNIC-TOC w as radiolabeled at high specific activities using tricine, ethylenediamined iacetic acid (EDDA), and tricine-nicotinic acid as coligand systems. Recept or binding was tested using AR42J rat pancreatic tumor cell membranes. inte rnalization and protein binding studies were performed, and biodistribution and tumor uptake were determined in AR42J tumor-bearing nude mice. Results : All Tc-99m-labeled HYNIC peptides showed retained somatostatin-receptor b inding affinities (K-d < 2.65 nM). Protein binding and internalization rate s were dependent on the coligand used. Specific tumor uptake between 5.8 an d 9.6 percentage injected dose per gram (%ID/g) was found for the Tc-99m-la beled peptides, compared with 4.3 %ID/g for In-111-DTPA-octreotide. Tricine as coligand showed higher activity levels in muscle, blood, and liver, whe reas tricine-nicotinic acid produced significant levels of activity in the gastrointestinal tract. EDDA showed the most promising overall biodistribut ion profile, with tumor-to-liver and tumor-to-gastrointestinal tract ratios similar to those obtained with In-111-DTPA-octreotide, lower ratios in blo od and muscle, but considerably higher tumor-to-kidney ratios. Conclusion: TOC can be radiolabeled to high specific activities using HYNIC as a bifunc tional chelator. The high specific tumor uptake, rapid blood clearance, and predominantly renal excretion make Tc-99m-EDDA-HYNIC-TOC a promising candi date for an alternative to In-111-DTPA-octreotide for tumor imaging.