The radiolanthanides
149Pm,
166Ho, and
177Lu have decay characteristics suitable for radioimmunotherapy (RIT)of cancer.
N-Hydroxysulfosuccinimidyl DOTA (DOTA-OSSu) and methoxy-DOTA (MeO-DOTA) were conjugatedto the anti-TAG-72 monoclonal antibody CC49 for radiolabeling with
149Pm,
166Ho, and
177Lu. While both DOTAconjugates could be labeled to high specific activity with
177Lu, MeO-DOTA afforded superior conjugate stability,radiolabeling, and radiochemical purity. Pilot biodistributions in nude mice bearing LS174T human colon carcinomaxenografts demonstrated that MeO-DOTA afforded higher tumor uptake and lower kidney retention of
177Lu thanDOTA-OSSu. The in vitro stability of
149Pm-,
166Ho-, and
177Lu-MeO-DOTA-CC49 was evaluated using serumand hydroxyapatite assays. Serum stability of radiolanthanide-labeled MeO-DOTA-CC49 followed a trend basedon the coordination energies of the radiometals, with
177Lu showing the highest stability after 96 to 168 h at 37
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C. In contrast, MeO-DOTA-CC49 labeled with all three radiolanthanides was >92% stable to hydroxyapatitechallenge for 168 h at 37
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C. Comprehensive biodistributions of
149Pm-,
166Ho-, and
177Lu-MeO-DOTA-CC49were obtained in LS174T-bearing nude mice. Maximum tumor uptakes were 100.0% ID/g for
149Pm at 96 h,69.5% ID/g for
166Ho at 96 h, and 132.4% ID/g for
177Lu at 168 h. Normal organ uptakes were generally low,except in the liver, spleen, and kidney at early time points. By 96 to 168 h postinjection, nontarget organ uptakedecreased to approximately 7% ID/g (kidney), 12% ID/g (spleen), and 20% ID/g (liver) for each radiolanthanide.When labeled with
149Pm,
166Ho, and
177Lu, MeO-DOTA-CC49 has potential for RIT of colorectal cancer andother carcinomas.