荒野 泰

An enhancement of the target/nontarget ratio of radioactivity levels enables reliable diagnosis and therapy using polypeptide radiopharmaceuticals in nuclear medicine. In the present study, we investigated the effects of the physicochemical properties of radiometabolites on the radioactivity pharmacokinetics after administration of Tc-99m-labeled polypeptides using 6-hydrazinopyridine-3-carboxylic acid (HYNIC). Four ternary ligands (L) [3-benzoylpyridine (BP), 3-acetylpyridine (AP), 3-nicotinic acid (NIC), pyridine (PY)] with different lipophilicity were selected as coligands for the preparation of Tc-99m-HYNIC-polypeptides. Each of the ternary ligands tested provided Tc-99m-HYNIC-labeled galactosyl-neoalbumin (NGA) and Fab fragments of high stability with high radiochemical purity. Moreover, after administration of each Tc-99m-HYNIC-labeled NGA into normal mice, the respective ternary ligand [Tc-99m](HYNIC-lysine)(tricine)(L) complexes were generated as final radiometabolites in the hepatic lysosome. The partition coefficients of [Tc-99m](HYNIC-lysine)(tricine)(BP), [99mTc](HYNIC-lysine)(tricine)(AP), [99mTc](FrYNIC-lysine)(tricine)(NIC), and [Tc-99m(HYNIC-lysine)(tricine)(PY) were determined to be -2.21, -2.37, -2.93, and -2.73, respectively. Elimination rates of these radiometabolites from the lysosome were enhanced in the order of increasing lipophilicity of the radiometabolites. After injection of the four Tc-99m-HYNIC-labeled Fab fragments into normal mice, blood clearances of radioactivity were similar while radioactivity elimination rates from the kidney were enhanced in the order of increasing lipophilicity of the radiometabolites. The present study indicated that the lipophilicity of the radiometabolites constitutes one important factor affecting their elimination rates from the tissues. Thus, as ternary ligands facilitate alteration of the physicochemical properties of radiometabolites, the use of ternary ligand complexes might be applicable for controlling the pharmacokinetics of Tc-99m-labeled polypeptides.

99mTc radiopharmaceuticals play an important role in widespread applications of nuclear medicine. When 99mTc radiopharmaceuticals first came into use, major efforts were directed toward the development of 99mTc radiopharmaceuticals for bone imaging and for the excretory functions of the liver and kidneys. In the past 20 years, a significant advance has been made in technetium chemistry, which provided 99mTc radiopharmaceuticals for assessment of regional cerebral and myocardial blood flow. Recent efforts have been directed toward the design of 99mTc-labeled compounds for estimating receptor or transporter functions. A number of bifunctional chelating agents that provide 99mTc labeled proteins and peptides of high in vivo stability with high radiochemical yields have also been developed. More recently, organometallic technetium and rhenium compounds have been introduced as another class of 99mTc radiopharmaceutical design. In this manuscript, recent progress in 99mTc radiopharmaceuticals is reviewed with the major emphasis laid on key innovations in this field to provide the 99mTc radiopharmaceuticals available today.