The synthesis of pteroyl-lys conjugates and its application as Technetium-99m labeled radiotracer for folate receptor-positive tumor targeting

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 7; pp. 2025 - 2029
• Main Authors: Guo, Hongjuan, Xie, Fang, Zhu, Meilin, Li, Yan, Yang, Zhi, Wang, Xuebin, Lu, Jie
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.04.2011; Elsevier
• Subjects: 99mTc; Animals; Biological and medical sciences; chemistry; Chromatography, High Pressure Liquid; Contrast media. Radiopharmaceuticals; Folate receptor; Folate-drug conjugates; folic acid; Folic Acid Transporters - metabolism; image analysis; Lysine - chemistry; Medical sciences; Mice; Mice, Nude; Neoplasms, Experimental - diagnostic imaging; Neoplasms, Experimental - metabolism; Pharmacology. Drug treatments; Pteroyl-lys-HYNIC; Radionuclide Imaging; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacology; Tumor imaging; 99mTc; Folate receptor; Tumor imaging; Pteroyl-lys-HYNIC; Folate-drug conjugates; Folate; Pyridine derivatives; Tc; Tissue; Technetium Complexes; Scintigraphic agent; Targeted drug; Hydrazone; Radioisotopic product; Chemical synthesis; Tumor cell; Labelled compound; Nicotinic acid derivatives; Biological receptor; Human; Rodentia; Epidermis; Transition metal Complexes; Diagnostic agent; Vertebrata; Mammalia; Cell line; Mouse; Animal; KB cell line; Distribution; Conjugated compound
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.02.014

The novel complex 99mTc(HYNIC-lys-pteroyl)(tricine/TPPTS) was able to specifically target the FR-positive tumor cells and tissues both in vitro and in vivo, highlighting its potential as an effective folate receptor targeted agent for tumor imaging. Aiming to develop a new 99mTc-labeled folate derivative for FR-positive tumor imaging, a simpler method has been established to synthesize the folate-drug conjugates with free α-carboxyl group. In this study, the conjugate pteroyl-lys-HYNIC was synthesized and labeled with 99mTc using tricine and TPPTS as co-ligands. The radiochemical purity of the final complex 99mTc(HYNIC-lys-pteroyl)(tricine/TPPTS), 5 was high (>98%), and it remained stable in saline and plasma over 6 h after preparation. The biologic evaluation results showed that the 99mTc labeled pteroyl-lys conjugate was able to specifically target the FR-positive tumor cells and tissues both in vitro and in vivo, highlighting its potential as an effective folate receptor targeted agent for tumor imaging.