PT - JOURNAL ARTICLE AU - Jean-Pierre Pouget AU - Lore Santoro AU - Laure Raymond AU - Nicolas Chouin AU - Manuel Bardiès AU - Eric Vivès AU - Pierre-Olivier Kotzki AU - Monique Pèlegrin AU - André Pèlegrin TI - Biological efficiency of 125I in targeted therapy of small solid tumors: In vitro and in vivo data DP - 2007 May 01 TA - Journal of Nuclear Medicine PG - 134P--134P VI - 48 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/48/supplement_2/134P.3.short 4100 - http://jnm.snmjournals.org/content/48/supplement_2/134P.3.full SO - J Nucl Med2007 May 01; 48 AB - 457 Objectives: Our study investigated both in vitro and in vivo, the biological efficiency of 125I according to whether it was localized at the surface, in the cytoplasm, or in the nucleus of tumor cells. Methods: Cytoplasmic targeting of A-431 and SK-OV-3 carcinoma cells was mediated by the anti-HER1 125I-m225 monoclonal antibody (mAb) and by the anti-HER2 125I-trastuzumab mAb, respectively. Both cell lines were transfected by the encoding gene for the carcinoembryonic antigen (CEA) such that the anti-CEA 125I-35A7 mAb could be used for cell surface targeting. Nuclear targeting was mediated by 125I-Tat peptide. In vitro toxicities of 125I-mAbs and of 125I-Tat were monitored by clonogenic assay and correlated to the mean irradiation dose delivered to the nucleus by using the MIRD cellular approach. In vivo efficiency of 125I-mAbs in the therapy of nude mice bearing small intraperitoneal tumors (<1mm) from A-431 and SK-OV-3 cells was also assessed. Results: Depending on the targeting model, we showed in vitro that toxicity of non-internalizing 125I-mAbs was either greater or similar to the one observed with internalizing mAbs. However, 125I-Tat targeting was shown to be between 2 and 5 five times more efficient in killing cells than labeled mAbs. Finally, in vivo experiments indicated that 125I-mAbs were highly efficient in the therapy of small peritoneal solid tumors. Conclusions: These results indicated that 125I-mAbs are promising therapeutic agents in the therapy of small solid tumors. Non internalizing mAbs should be considered as efficient, if not more, as internalizing mAbs. Research Support (if any): This work was supported by the Electricité de France-Service de Radioprotection, Ligue National Contre le Cancer, CAMPLP.