11C-Colchicine distribution in tissues of colchicine -sensitive and -resistant neuroblastoma xenografts

Journal Article · Mon May 01 04:00:00 EDT 1995 · Journal of Nuclear Medicine

OSTI ID:441640

Mehta, B M; Levchenko, A; Broussard, E ^[1]

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1. Memorial Sloan Kettering Cancer Center, NY (United States); and others

Multidrug resistance (MDR), a major obstacle in chemotherapy of cancer is thought to be due to the overexpression of a membrane P-glycoprotein (Pgp). P-glycoprotein acts as an energy activated efflux pump, reducing the effective drug concentrations from the MDR tumors. Our earlier studies using neuroblastoma cell lines BE(2)-C (-sensitive), and BE(2)-C/CHCb (-resistant) to colchicine (CHC), showed that uptake of 3H-CHC as well as 14C-CHC in sensitive tumors was twice as much as in resistant tumors. In view of this finding we synthesized 11C-CHC to study the distribution in xenografted animals, since 11C-CHC can be used a a Positron Emission Tomography (PET) tracer in humans. Two groups of Balb/c nude mice (5 animals each) xenografted with BE(2)-C and BE(2)-C/CHCb cells (10 x 10{sup 6} cells per animal) were injected iv retroorbitally with 200 {mu}Ci/100 {mu}l of 11C-CHC per animal. One hour after injection animals were sacrificed by cervical dislocation and blood, tissues and tumors were excised to determine the amount of radioactivity. 11C-CHC biodistribution compared well with 3H-CHC and 14C-CHC distribution. Tumor uptake in sensitive was 1.21 {plus_minus} 0.84% ID/g compared to 0.76 {plus_minus} 0.43% ID/g in resistant tumors. Tumor to blood ratios is sensitive and resistant tumors were 1.62 {plus_minus} 0.41 and 0.69 {plus_minus}0.30 respectively. 11C-Isocolchicine, a byproduct of 11C-CHC synthesis, on the other hand had only 25% uptake as compared to 11C-CHC in both sensitive and resistant tumors. We interpret these results to mean that 11C-CHC behaves similarly to other forms of CHC as a marker of the MDR phenotype. In the future, we plan to use 11C-CHC for identification of MDR status of tumors in vivo using PET scanning.

• DOE Contract Number: FG02-86ER60407
• OSTI ID: 441640
• Report Number(s): CONF-950603--
• Journal Information: Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 36; ISSN JNMEAQ; ISSN 0161-5505
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ANIMALS
CARBON 11
CHEMOTHERAPY
COLCHICINE
GLYCOPROTEINS
MICE
NEOPLASMS
POSITRON COMPUTED TOMOGRAPHY
TISSUE DISTRIBUTION
UPTAKE