Synthesis and evaluation of Tc-99m DTPA-glutathione as a non-invasive tumor imaging agent in a mouse colon cancer model.

Abstract

PURPOSE:

Glutathione (GSH) plays a critical role in detoxification reactions by reducing the levels of reactive oxygen species in cancer cells. This study aimed to develop technetium (Tc)-99m diethylenetriaminepentaacetic acid (DTPA)-GSH as a tumor imaging agent, and to evaluate the diagnostic performance of Tc-99m DTPA-GSH in terms of its ability to differentiate tumors from inflammatory lesions.

METHODS:

DTPA-GSH was synthesized by reaction of GSH with DTPA anhydride under anhydrous conditions in a nitrogen atmosphere. DTPA-GSH was then reacted with Tc-99m sodium pertechnetate in a tin (II) chloride (SnCl2) solution. Gamma camera imaging was performed after intravenous injection of Tc-99m DTPA-GSH into a mouse CT-26 colon cancer model, or a mouse model of inflammation induced by the intramuscular injection of Freund's complete adjuvant.

RESULTS:

DTPA-GSH was successfully prepared via a straightforward synthetic procedure and radiolabeled with Tc-99m at a high labeling efficiency (>95%). Tc-99m DTPA-GSH was strongly internalized by tumors in colon cancer model mice, with the tumor-to-normal muscle ratio of the complex reaching 4.3±0.9 at 4 h. By contrast, Tc-99m DTPA-GSH showed relatively weak uptake in inflammatory lesions (target-to-non-target ratio=2.0±0.3 at 4 h). A competition study showed that the uptake of Tc-99m DTPA-GSH into tumors was blocked by co-injection with high concentrations of free GSH.

CONCLUSIONS:

The results of this work indicate that Tc-99m DTPA-GSH is a good candidate for development as a non-invasive tumor imaging agent. Furthermore, Tc-99m DTPA-GSH effectively distinguished between cancerous tissue and inflammatory lesions.

• Authors: Dae-Weung Kim, Woo Hyoung Kim, Myoung Hyoun Kim, Chang Guhn Kim, Chang-Sok Oh, Jung-Joon Min
• Journal: Annals of nuclear medicine (Ann Nucl Med) Vol. 28 Issue 5 Pg. 447-54 (Jun 2014) ISSN: 1864-6433 [Electronic] Japan
• PMID: 24627293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glutathione
• Technetium Tc 99m Pentetate

Topics

• Animals
• Chemistry Techniques, Synthetic
• Colonic Neoplasms (diagnostic imaging, metabolism)
• Diagnosis, Differential
• Disease Models, Animal
• Female
• Glutathione (chemistry)
• Mice
• Mice, Inbred BALB C
• Radionuclide Imaging
• Technetium Tc 99m Pentetate (chemical synthesis, chemistry, pharmacokinetics)
• Tissue Distribution