RT Journal Article SR Electronic T1 Immune PET with 89Zr anti-CD133 antibody can monitor colon cancer CD133 expression and its modulation by chemotherapy JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1258 OP 1258 VO 62 IS supplement 1 A1 Jung, Kyung-Ho A1 Lee, Jin Hee A1 Park, Jin-Won A1 Kim, Mina A1 Cho, Young Seok A1 LEE, KYUNG-HAN YR 2021 UL http://jnm.snmjournals.org/content/62/supplement_1/1258.abstract AB 1258Objectives: The goal of this study was to develop an 89Zr-labeled anti-CD133 immune PET technique that can image tumor CD133 and monitor chemotherapy-mediated modulation of expression in vivo. Methods: Anti-CD133 antibodies underwent sulfohydryl moiety-specific conjugation with maleimide-deferoxamine followed by 89Zr labeling. Radiochemical purity, specific activity and radiolabel stability was assessed. Cell binding assays and Western blotting was performed. In vivo pharmacokinetics and biodistribution were assessed and PET studies were performed in mice. Results: 89Zr-CD133 IgG was efficiently synthesized by site-specific conjugation. High CD133 expressing HT29 colon cancer cells showed substantially greater 89Zr-CD133 IgG binding compared to weak expressing CT26 colon cancer cells, and complete reduction of binding by excess cold antibody confirmed excellent target specificity. Among chemotherapeutic agents, src inhibition with PP2 or dasatinib stimulated HT29 cell CD133 expression >4-fold, whereas COX-2 inhibition with celecoxib dose-dependently suppressed CD133 expression to 19.9 ± 2.1% of basal level. These effects were accompanied by significant increases (170.2 ± 2.7% and 160.9 ± 16.2%) and reduction (50.3 ± 10.9% of basal level) of 89Zr-CD133 IgG binding, respectively. When 89Zr-CD133 IgG was injected into HT29 tumor-bearing mice, PET/CT displayed high-contrast tumor uptake at 6 days post-injection that was suppressed by excess cold antibody. Biodistribution studies showed high tumor uptake of 11.4 ± 1.3 %ID/gm, compared to a lower blood activity of 4.9 ± 1.6 %ID/gm. In the animals, celecoxib treatment substantially decreased tumor uptake in a manner that reflected reductions in tumor CD133 expression Conclusions: 89Zr-CD133 IgG PET can noninvasively image tumor CD133 expression and may be useful for monitoring chemotherapy-mediated tumor CD133 modulation in living subjects.