TY - JOUR
T1 - Tumor detection using 18F-labeled matrix metalloproteinase-2 inhibitor
AU - Furumoto, Shozo
AU - Takashima, Kyoka
AU - Kubota, Kazuo
AU - Ido, Tatsuo
AU - Iwata, Ren
AU - Fukuda, Hiroshi
N1 - Funding Information:
This work was supported by Grants-in-Aid (No.12470183 and 13470177) for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2003/2
Y1 - 2003/2
N2 - Matrix metalloproteinase-2 (MMP-2) is a key enzyme involved in tumor invasiveness. (2R)-2- [4-(6-[18F]Fluorohex-1-ynyl)-benzenesulfonylamino]-3-methylbutyric acid ([18F]SAV03), a new fluorine-18 labeled MMP-2 inhibitor developed for tumor imaging with PET, was biologically evaluated using in vivo tumor model. Enzymatic MMP-2 assay of SAV03 yielded an IC50 value of 1.9 μM. Biodistribution study of [18F]SAV03 using Ehrlich tumor bearing mice showed that the uptake in tumor was higher than in other organs, except for the liver, small intestine, and bone. When [18F]SAV03M, a methyl ester of [18F]SAV03, was used as a prodrug, the uptake in liver at 30 min after injection decreased by half and that in tumor increased by 2.4 times, compared with [18F]SAV03. Radio-thin-layer chromatographic analysis of [18F]SAV03M metabolites revealed that administered [18F]SAV03M was easily converted to the parent drug in vivo and accumulated in tumor tissue. Thus, [18F]SAV03M is suitable as the prodrug of [18F]SAV03 with potent efficacy. Whole body autoradiography using [18F]SAV03M also indicated tumor-specific accumulation of radioactivity, while higher accumulations in bone and intestinal contents were observed. Our results suggest that [18F]SAV03M could be potentially suitable for tumor imaging with PET.
AB - Matrix metalloproteinase-2 (MMP-2) is a key enzyme involved in tumor invasiveness. (2R)-2- [4-(6-[18F]Fluorohex-1-ynyl)-benzenesulfonylamino]-3-methylbutyric acid ([18F]SAV03), a new fluorine-18 labeled MMP-2 inhibitor developed for tumor imaging with PET, was biologically evaluated using in vivo tumor model. Enzymatic MMP-2 assay of SAV03 yielded an IC50 value of 1.9 μM. Biodistribution study of [18F]SAV03 using Ehrlich tumor bearing mice showed that the uptake in tumor was higher than in other organs, except for the liver, small intestine, and bone. When [18F]SAV03M, a methyl ester of [18F]SAV03, was used as a prodrug, the uptake in liver at 30 min after injection decreased by half and that in tumor increased by 2.4 times, compared with [18F]SAV03. Radio-thin-layer chromatographic analysis of [18F]SAV03M metabolites revealed that administered [18F]SAV03M was easily converted to the parent drug in vivo and accumulated in tumor tissue. Thus, [18F]SAV03M is suitable as the prodrug of [18F]SAV03 with potent efficacy. Whole body autoradiography using [18F]SAV03M also indicated tumor-specific accumulation of radioactivity, while higher accumulations in bone and intestinal contents were observed. Our results suggest that [18F]SAV03M could be potentially suitable for tumor imaging with PET.
KW - Autoradiography
KW - Fluorine-18
KW - Matrix metalloproteinase
KW - Matrix metalloproteinase inhibitor
KW - Tumor imaging
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U2 - 10.1016/S0969-8051(02)00393-1
DO - 10.1016/S0969-8051(02)00393-1
M3 - Article
C2 - 12623110
AN - SCOPUS:0037291678
VL - 30
SP - 119
EP - 125
JO - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
JF - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
SN - 0969-8051
IS - 2
ER -