Carbon-11 labeled σ2 receptor ligands for imaging breast cancer

Four conformationally flexible benzamide analogs having a high affinity and outstanding selectivity for σ2 versus σ1 receptors were synthesized and radiolabeled with carbon-11 by reaction with [11C]methyl iodide. The four 11C-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-11C)-N-(4-(3,4-dihydro-6,7-dimethoxy-isoquinolin-2(1H)-yl)butyl)-5-methylbenzamide ([11C]2), had a high tumor uptake and suitable tumor/background ratio for imaging purposes. Blocking studies were consistent with the labeling of σ2 receptors in vivo. A study comparing the in vivo properties of [11C]2 and 18F-3′-fluoro-3′-deoxy-l-thymidine ([18F]FLT) indicated that [11C]2 had either similar (lung, fat) or better (blood, muscle) tumor/organ ratios than [18F]FLT in the tissues that are important for breast tumor imaging. Consequently, [11C]2 is a potential radiotracer for imaging the proliferative status of breast tumors in vivo with PET.