Study the 99m Tc-labeling conditions of HYNIC-conjugated peptides from a new perspective: Introduction to the term radio-stoichiometry.

Specific tumor uptake of peptide radiopharmaceuticals depends on tumor binding affinity and their radiochemical purity. Several important parameters that influence the 99m Tc-labeling and consequently the radiochemical purity of HYNIC-conjugated peptide are radionuclide activity, the amount of peptide, the amount of co-ligands, and the amount of reducing agents (stannous ion). In this review article, we have attempted studying these parameters in the HYNIC-conjugated peptides (somatostatin, cholecystokinin/gastrin, bombesin, and RGD analogs) from a new perspective to obtain most used and optimized radio-stoichiometric relationships. One of the most important results in this review is that for 99m Tc-labeling of HYNIC-conjugated peptides, it is better to consider the most calculated mole ratio between technetium-99m and the peptide (mole ratio of technetium-99m to the peptide 1:200 - 400). The statistical results also show that among these 99m Tc-labeled peptides the most used and favorable co-ligands is tricine/EDDA with two to one (2:1) mole ratios. These optimized radio-stoichiometric relationships, favorable co-ligands mole ratio, and applicable radiolabeling points can greatly improve the labeling process of the HYNIC-conjugated peptides, by reducing trial and error, increasing specific activity and saving materials.