RT Journal Article SR Electronic T1 Antitumor Effects of a Human Dimeric Antibody Fragment 131I-AFRA-DFM5.3 in a Mouse Model for Ovarian Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1938 OP 1946 DO 10.2967/jnumed.110.086819 VO 52 IS 12 A1 Zacchetti, Alberto A1 Martin, Franck A1 Luison, Elena A1 Coliva, Angela A1 Bombardieri, Emilio A1 Allegretti, Marcello A1 Figini, Mariangela A1 Canevari, Silvana YR 2011 UL http://jnm.snmjournals.org/content/52/12/1938.abstract AB AFRA-DMF5.3 is a human antibody fragment that, as a dimer, specifically binds to the α-folate receptor (FR) on ovary cancer cells. Pharmacokinetic and biodistribution parameters of 131I-AFRA-DFM5.3 after intravenous administration in animal models support its potential therapeutic use. We evaluated its preclinical specificity and therapeutic efficacy in tumor models. Methods: A negative control, AFRA-DFM6.1, was obtained by protein engineering. The activity and specificity of 131I-AFRA-DFMs were evaluated by systemic administration (intravenous) in subcutaneous tumor xenograft–bearing nude mice. Pharmacokinetics, biodistribution, and efficacy were assessed by intraperitoneal administration of 131I-AFRA-DFM5.3 in nude mice bearing 2 different intraperitoneal ovarian carcinoma xenografts. Treatments were tested at different doses and as single or double administrations 1 wk apart. Results: In subcutaneous models, 131I-AFRA-DFM5.3, but not the negative control, was found to reside on FR-positive tumor masses and significantly reduced tumor growth. In intraperitoneal models, early accumulation on free-floating clumps of ovarian cancer cells and solid peritoneal masses was evident after 1 h, and tumor uptake was stable for up to 3 h. The high tumor uptake determined the efficacy of 131I-AFRA-DFM5.3. The best antitumor activity, with more than 50% of treated animals cured, was achieved with 2 locoregional treatments of intraperitoneally growing tumors on days 2 and 9. Conclusion: These results suggest that radioimmunotherapy with 131I-AFRA-DFM5.3 is feasible and leads to significantly prolonged survival. These preclinical data provide the basis for the rationale design of therapeutic treatments of ovarian cancer patients with a radiolabeled anti-FR antibody fragment.