Targeting an ultrasound contrast agent to folate receptors on ovarian cancer cells: feasibility research for ultrasonic molecular imaging of tumor cells.

Objective. The purpose of the study was to synthesize and characterize folate-targeted microbubbles (MBF) as an ultrasound contrast agent and to evaluate their affinity to the folate receptor (FR) in vitro. Methods. Folate-targeted microbubbles were prepared by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-famino(polyethylene glycol)-2000]-folate into the lipid membrane of microbubbles. The diameter and concentration of the MBF were determined by a cell counter and sizer. The MBF control microbubbles (MBC), and MBF with a free folic acid blockade were tested for binding specificity to human ovarian carcinoma SKOV3 cells, which overexpress the FR, by microscopy and confocal imaging, respectively. Results. The basic physical characteristics of MBF were similar to those of MBC. In the cell binding test, the adherence efficiency of MBF to the SKOV3 cells (mean SD, 16 +/- 5 microbubbles per cell; P < .01) was significantly higher than that of MBC (0.7 +/- 0.4 microbubbles per cell) or MBF with the free folic acid blockade (0.7 +/- 0.6 microbubbles per cell). Conclusions. Folate-targeted microbubbles showed high affinity to SKOV3 cells with FR overexpression. They are potentially useful for ultrasonic molecular imaging and treatment of FR-positive tumors and warrant further investigation.