Carbon-11 labeled sigma2 receptor ligands for imaging breast cancer.

Abstract

Four conformationally flexible benzamide analogs having a high affinity and outstanding selectivity for sigma(2) versus sigma(1) receptors were synthesized and radiolabeled with carbon-11 by reaction with [(11)C]methyl iodide. The four (11)C-labeled radiotracers were evaluated for their potential to image the proliferative status of breast tumors with positron emission tomography (PET). In vivo studies in female BALB/C mice bearing EMT-6 breast tumors showed that one radiotracer, (2-methoxy-(11)C)-N-(4-(3,4-dihydro-6,7-dimethoxy-isoquinolin-2(1H)-yl)butyl)-5-methylbenzamide ([(11)C]2), had a high tumor uptake and suitable tumor/background ratio for imaging purposes. Blocking studies were consistent with the labeling of sigma(2) receptors in vivo. A study comparing the in vivo properties of [(11)C]2 and (18)F-3'-fluoro-3'-deoxy-L-thymidine ([(18)F]FLT) indicated that [(11)C]2 had either similar (lung, fat) or better (blood, muscle) tumor/organ ratios than [(18)F]FLT in the tissues that are important for breast tumor imaging. Consequently, [(11)C]2 is a potential radiotracer for imaging the proliferative status of breast tumors in vivo with PET.

• Authors: Zhude Tu, Carmen S Dence, Datta E Ponde, Lynne Jones, Kenneth T Wheeler, Michael J Welch, Robert H Mach
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 32 Issue 5 Pg. 423-30 (Jul 2005) ISSN: 0969-8051 [Print] United States
• PMID: 15982571 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carbon Radioisotopes
• Ligands
• Receptors, sigma

Topics

• Animals
• Carbon Radioisotopes
• Female
• Ligands
• Mammary Neoplasms, Experimental (diagnostic imaging)
• Mice
• Mice, Inbred BALB C
• Positron-Emission Tomography
• Receptors, sigma (analysis, metabolism)