TY - JOUR T1 - Pretargeted <sup>177</sup>Lu Radioimmunotherapy of Carcinoembryonic Antigen–Expressing Human Colonic Tumors in Mice JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1780 LP - 1787 DO - 10.2967/jnumed.110.079376 VL - 51 IS - 11 AU - Rafke Schoffelen AU - Winette T.A. van der Graaf AU - Gerben Franssen AU - Robert M. Sharkey AU - David M. Goldenberg AU - William J. McBride AU - Edmund A. Rossi AU - Annemarie Eek AU - Wim J.G. Oyen AU - Otto C. Boerman Y1 - 2010/11/01 UR - http://jnm.snmjournals.org/content/51/11/1780.abstract N2 - Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies in combination with a radiolabeled peptide reduces the radiation dose to normal tissues, especially the bone marrow. In this study, the optimization, therapeutic efficacy, and toxicity of PRIT of colon cancer with a 177Lu-labeled peptide was determined in mice with carcinoembryonic antigen (CEA)-expressing human tumors. Methods: To obtain the optimal therapeutic efficacy, several strategies were evaluated to increase the total amount of radioactivity targeted to subcutaneous LS174T colon cancer tumors in BALB/c nude mice. First, the maximum amount of bispecific anti-CEA and antihapten antibody TF2 and the peptide IMP288 that could be targeted was determined. Second, the tumor targeting of repeated administrations of radiolabeled IMP288 was investigated. Mice received 1 TF2 injection, followed by multiple IMP288 injections (3-h interval) or multiple cycles, with each IMP288 administration preceded by a new TF2 injection (72-h interval). PRIT was administered at maximum doses of TF2 and 177Lu-labeled IMP288 in groups of 9 mice with subcutaneous LS174T tumors. Mice received 1, 2, or 3 successive cycles of treatment (26 MBq/mouse/cycle) or carrier only. The primary endpoint was survival; secondary endpoints were tumor growth, body weight, bone marrow, and renal toxicity. Results: The highest amount of radioactivity delivered to a subcutaneous colon tumor was achieved by the administration of 5.0 nmol of TF2 and 0.28 nmol of IMP288 in 3 successive cycles, with each IMP288 preceded by a new TF2 injection (72-h interval). PRIT effectively delayed tumor growth and prolonged survival significantly. Higher activity doses, administered in successive cycles, correlated with longer survival: the median survival of untreated mice was 13 d (range, 6–20 d), whereas that of mice treated with 1, 2, or 3 cycles of PRIT was 24 (range, 24–31 d), 45 (range, 38 ≥ 130 d), and 65 (range, 48 ≥ 130 d) days, respectively. Toxicity was limited: no significant changes in mean body weight were measured. Minimal changes in leukocyte counts were measured at 2 and 3 wk after injection, with full recovery within 7 wk after treatment. Platelet counts were unaffected. Serum creatinine levels were not increased significantly; thus, there was no indication of acute renal toxicity. Conclusion: This study indicates that PRIT in mice is an effective treatment modality against colon cancer, with limited toxicity. ER -