Pulsed High-Intensity Focused Ultrasound Enhances Uptake of Radiolabeled Monoclonal Antibody to Human Epidermoid Tumor in Nude Mice
Alfia Khaibullina 1,
Beom-Su Jang 2,
Haihao Sun 1,
Nhat Le 2,
Sarah Yu 2,
Victor Frenkel 1,
Jorge A. Carrasquillo 2,
Ira Pastan 3,
King C.P. Li 1,
and
Chang H. Paik 2*
1 Department of Radiology, Clinical Center, National Institutes of Health, Bethesda, Maryland
2 Department of Nuclear Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
3 Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
* To whom correspondence should be addressed. E-mail: cpaik{at}mail.nih.gov.
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Abstract |
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The aim of this study was to determine if pulsed high-intensity focused ultrasound (HIFU) exposures could enhance tumor uptake of 111In-MX-B3, a murine IgG1
monoclonal antibody directed against the Ley antigen. Methods: MX-B3 was labeled with 111In, purified, and confirmed for its binding to the antigen-positive A431 cell line. Groups of nude mice were inoculated subcutaneously with A431 tumor cells on both hind flanks. A tumor on one flank was treated with pulsed-HIFU; the other tumor was used as an untreated control. Within 10 min after the HIFU exposure, the mice received intravenous 111In-MX-B3 for imaging and biodistribution studies. Mice were euthanized at 1, 24, 48, and 120 h after injection for biodistribution studies. Results: The HIFU exposure shortened the peak tumor uptake time (24 vs. 48 h for the control) and increased the peak tumor uptake value (38 vs. 25 %ID/g [percentage injected dose per gram] for the control). The HIFU effect on enhancing tumor uptake was greater at earlier times up to 24 h, but the effect was gradually diminished thereafter. The HIFU effect on enhancing tumor uptake was substantiated by nuclear imaging studies. HIFU also increased the uptake of the antibody in surrounding tissues, but the net increase was marginal compared with the increase in tumor uptake. Conclusion: This study demonstrates that pulsed-HIFU significantly enhances the delivery of 111In-MX-B3 in human epidermoid tumors xenografted in nude mice. The results of this pilot study warrant further evaluation of other treatment regimens, such as repeated HIFU exposures for greater delivery enhancement of antibodies labeled with cytotoxic radioisotopes or pulsed-HIFU exposure in addition to a combined therapy of 90Y-B3 and taxol to enhance the synergistic effect.
Key Words:
pulsed-HIFU, enhanced tumor uptake, 111In-MX-B3, A431 tumor
