Effect of “co-ligand” on the biodistribution of 99mTc-labeled hydrazino nicotinic acid derivatized chemotactic peptides

• Published in: Nuclear medicine and biology 1995, Vol.22 (1), p.25-30
• Main Authors: Babich, J.W., Fischman, A.J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Chemotactic Factors - pharmacokinetics; Contrast media. Radiopharmaceuticals; Ligands; Male; Medical sciences; Molecular Sequence Data; Niacinamide - pharmacokinetics; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Technetium; Tissue Distribution
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/0969-8051(94)00081-T

Hydrazinonicotinamide (HYNIC) derivatized chemotactic peptides radiolabeled with 99mTc- (via 99mTc-glucoheptonate) have been demonstrated to be useful for infection imaging [ J. Nucl. Med. 34, 1964–1974 (1993)]. Since HYNIC can occupy only two sites of the technetium co-ordination sphere, the labeled product most probably contains additional ligands. Thus we hypothesized that glucoheptonate serves this role by acting as a “‘co-ligand’”. Due to the low molecular weight of the chemotactic peptides, the “co-ligand” used for technetium labeling could have profound effects on biodistribution. To evaluate this possibility, we measured the biodistribution of 99mTc-labeled For-MLFKHYNIC radiolabeled using four different “co-ligand”s: glucarate, glucoheptonate, mannitol and glucamine, providing a small series of hydroxyl-backbone ligands which differ in the number and type of ionizable functional groups present. Each preparation was injected into groups of 6 rats (~ 10 μCi/rat) and biodistribution was determined at 5, 30, 60 and 120 min. Although small differences in biodistribution were detected in most tissues, the Most prominent differences ( P < 0.01) were observed in lung (glucoheptonate, glucarate > mannitol ⪢ glucamine), liver (glucarate, glucoheptonate, mannitol ⪢ glucamine), kidney (mannitol > glucarate, glucoheptonate, glucamine), spleen (glucarate ⪢ glucoheptonate, mannitol ⪢ glucamine) and GI-tract (glucarate, glucamine ⪢ gluco-heptonate ⪢ mannitol). These results provide support for the “co-ligand” hypothesis and indicate that the nature of the “co-ligand” can have profound effects on biodistribution. Although radiolabeling using glucamine as the “co-ligand” results in the lowest concentrations of radioactivity in most organs, the extremely low concentration of mannitol-labeled peptide in the GI-tract suggests that this may be the “co-ligand” of choice for most applications.