Preparation and evaluation of fluorine-18-labeled insulin as a molecular imaging probe for studying insulin receptor expression in tumors.
A convenient emulsion-based labeling method was used to synthesize fluorine-18-labeled insulin specifically B(1)-(4-[(18)F]fluorobenzoyl)insulin ((18)F-4b) in 6% overall radiochemical yield in 240 min. In vitro screening in MCF7 breast cancer cells demonstrated that the nonradioactive analogue (19)F-4a effectively competed with (125)I-insulin for the insulin receptor (IC50 = 10.6 nM) comparable to that for insulin (IC50 = 7.4 nM). (18)F-4b was also more stable than (125)I-insulin in mouse plasma with 50% remaining intact after 30 min. A biodistribution study in normal mice showed initial uptake of the tracer in the kidneys, liver, and gall bladder but rapid clearance via the urine/bladder which was also observed in murine models bearing insulin receptor positive tumors.
Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
Dong Hyun
DH
Kim
Megan
M
Blacker
John F
JF
Valliant
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D015335:Molecular Probes; D011972:Receptor, Insulin / Q000378:metabolism*; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D007328:Insulin; D015335:Molecular Probes; D011972:Receptor, Insulin