Preparation and preliminary evaluation of 4-[211At]astato-N-piperidinoethyl benzamide.

Abstract

The potential therapeutic agent, 4-[211At]astato-N-piperidinoethyl benzamide (4-APAB) was synthesized via a halodestannylation reaction. Radiochemical yields were 69% for a 5 min reaction and reached 74% by 25 min, whereas 82% radiochemical yields were obtained under similar reaction conditions for radioiodination. A simplified procedure was adopted for the purification of the target compound. In vitro binding of 4-APAB to SK-MEL 28 melanoma and D247 glioma cell lines was 20.7 +/- 1.3% and 12.2 +/- 1.3%, respectively. In comparison, binding of 4-[131I]iodo-N-piperidinoethyl benzamide (4-IPAB) to SK-Mel 28 cells was 13.9 +/- 1.9%. Paired label biodistribution studies were performed in normal Balb/c mice using 4-IPAB and 4-APAB. Thyroid uptake at 1, 2, and 6 h was significantly higher for 4-APAB. Differences in liver accumulation between the two compounds were small but statistically significant at most time points. A higher accumulation of 211At compared with 131I was observed in lungs and spleen at all time points studied. These results indicate that 4-APAB is not stable in vivo, suggesting the need for a better sigma receptor ligand for use in 211At.

• Authors: P K Garg, C S John, M R Zalutsky
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 22 Issue 4 Pg. 467-73 (May 1995) ISSN: 0969-8051 [Print] United States
• PMID: 7550023 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 4-astato-N-piperidinoethylbenzamide
• Antineoplastic Agents
• Benzamides
• Iodine Radioisotopes
• Piperidines
• 4-iodo-N-piperidinoethylbenzamide
• Astatine

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, metabolism, pharmacokinetics)
• Astatine (metabolism, pharmacokinetics)
• Benzamides (chemical synthesis, metabolism, pharmacokinetics)
• Brain (metabolism)
• Cell Line
• Cell Membrane (metabolism)
• Glioma
• Humans
• Iodine Radioisotopes (metabolism, pharmacokinetics)
• Lung (metabolism)
• Melanoma
• Mice
• Mice, Inbred BALB C
• Piperidines (chemical synthesis, metabolism, pharmacokinetics)
• Spleen (metabolism)
• Structure-Activity Relationship
• Time Factors
• Tissue Distribution