Carbon-11 labeled sigma2 receptor ligands for imaging breast cancer.
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.
Tu
Zhude
Z
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Dence
Carmen S
CS
Ponde
Datta E
DE
Jones
Lynne
L
Wheeler
Kenneth T
KT
Welch
Michael J
MJ
Mach
Robert H
RH
D000818:Animals; D002250:Carbon Radioisotopes; D005260:Female; D008024:Ligands; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography; D017480:Receptors, sigma / Q000032:analysis* / Q000378:metabolism
D002250:Carbon Radioisotopes; D008024:Ligands; D017480:Receptors, sigma