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Comparison of ²²⁵Ac, ²¹³Bi (-emitters) and ⁹⁰Y (β-emitter) labeled antibody against early stage pulmonary metastasis in a rat HER-2/neu transgenic mouse model

¹ Radiology, Johns Hopkins University, Baltimore, Maryland; ² European Commission, DG JRC, Institute for Transuranium Elements, Karlsruhe, Germany

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Objectives: The targeted -emitters ²²⁵Ac and ²¹³Bi hold promise in the treatment of micrometastases. We compared the efficacy of these to the β-emitter, ⁹⁰Y-labeled HER-2/neu antibody 7.16.4 against pulmonary metastases.

Methods: Transgenic neu-N mice were treated with 0.4, 120 or 120 µCi ²²⁵Ac-, ²¹³Bi-, or ⁹⁰Y-7.16.4 (n=3,5,5), 3 or 18 days after i.v. injection of 10⁵ mammary carcinoma cells. The MTD was chosen for each radionuclide.

Results: Median survival times of 85 days (p=0.01), 65 days (p=0.002) and 50 days (p=0.01) for ²²⁵Ac-, ²¹³Bi- and ⁹⁰Y-7.16.4, respectively, compared to 40.5 days in the untreated group (n=5) were obtained; median survival between ²²⁵Ac-, ²¹³Bi- treated groups and ⁹⁰Y-7.16.4 treated group were significantly different (p=0.01, p=0.04). Survival of the ²²⁵Ac treated group was longer than the ²¹³Bi treated group. (p=0.048). When the treatment was initiated at a late stage of metastatic progression (18 days after i.v. injection of tumor cells), the group treated with ²¹³Bi-7.16.4 (n=5) had a median survival time of 51 days while the group treated with ⁹⁰Y-7.16.4 (n=5) had a similar median survival time of 50 days. (p=0.76).

Conclusions: These results show that early lung metastases are best treated with targeted -particles. The short, 45 min. half-life of ²¹³Bi was not an obstacle to therapy. Response to ⁹⁰Y was independent of treatment time-post tumor inoculation. This may reflect the lower dose per cell needed for tumor control of few cells and the higher per cell dose needed for a greater number of cells. At a larger tumor burden, the dose per cell is increased due to cross-fire.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Song, H. Articles by Sgouros, G. PubMed Articles by Song, H. Articles by Sgouros, G.