Synthesis and evaluation of 99mTc(CO)(3)-DTPA-folate as a folate-receptor-targeted radiopharmaceutical.

Abstract

A folate-receptor-targeted 99mTc-radiopharmaceutical, [99mTc]Tc(CO)(3)DTPA-folate, was prepared by heating [99mTc]Tc(CO)(3)(H(2)O)(3)(+) in an aqueous solution of the previously reported DTPA-folate conjugate. The radiotracer was HPLC purified (> 98% radiochemical purity) and evaluated in vitro and in vivo as an agent for targeting folate-receptor-positive cells. [99mTc]Tc(CO)(3)DTPA-folate experienced high, folate-receptor-specific uptake in human KB tumor cells. Intravenous administration of [99mTc]Tc(CO)(3)DTPA-folate to athymic mice bearing KB cell tumor xenografts resulted in 99mTc tumor uptake of 1.8 +/- 0.5 and 3.3 +/- 0.2%ID/g (n = 3) at 30 minutes and 4 hours post-injection, respectively. Tumor uptake was reduced when folic acid was co-administered with the intravenous [99mTc]Tc(CO)(3)DTPA-folate, consistent with radiopharmaceutical localization being mediated by the folate receptor.

• Authors: David P Trump, Carla J Mathias, Zhenfan Yang, Philip S Low, Mary Marmion, Mark A Green
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 29 Issue 5 Pg. 569-73 (Jul 2002) ISSN: 0969-8051 [Print] United States
• PMID: 12088727 (Publication Type: Evaluation Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carrier Proteins
• Folate Receptors, GPI-Anchored
• Organotechnetium Compounds
• Radiopharmaceuticals
• Receptors, Cell Surface
• technetium Tc 99m tricarbonyl DTPA-folate
• Folic Acid

Topics

• Animals
• Carrier Proteins (metabolism)
• Folate Receptors, GPI-Anchored
• Folic Acid (analogs & derivatives, chemical synthesis, pharmacokinetics, pharmacology)
• Humans
• KB Cells (diagnostic imaging, metabolism)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Organotechnetium Compounds (chemical synthesis, pharmacokinetics)
• Radioligand Assay (methods)
• Radionuclide Imaging
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics)
• Receptors, Cell Surface
• Reproducibility of Results
• Sensitivity and Specificity
• Tissue Distribution
• Transplantation, Heterologous