Lani
11-19-2009, 12:13 PM
Future treatment of her2+ Stage IVs, or could they use smaller amounts to same effect with less kidney toxicity in Stage I-IIIs?
(remember, mice are short-lived)
perhaps giving a few treatments, followed by dialysis??Cancer Res. 2009 Nov 17. [Epub ahead of print]
Radioimmunotherapy of Breast Cancer Metastases with {alpha}-Particle Emitter 225Ac: Comparing Efficacy with 213Bi and 90Y.
Song H, Hobbs RF, Vajravelu R, Huso DL, Esaias C, Apostolidis C, Morgenstern A, Sgouros G.
Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, and Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland and Institute for Transuranium Elements, Karlsruhe, Germany.
alpha-Particles are suitable to treat cancer micrometastases because of their short range and very high linear energy transfer. alpha-Particle emitter (213)Bi-based radioimmunotherapy has shown efficacy in a variety of metastatic animal cancer models, such as breast, ovarian, and prostate cancers. Its clinical implementation, however, is challenging due to the limited supply of (225)Ac, high technical requirement to prepare radioimmunoconjugate with very short half-life (T(1/2) = 45.6 min) on site, and prohibitive cost. In this study, we investigated the efficacy of the alpha-particle emitter (225)Ac, parent of (213)Bi, in a mouse model of breast cancer metastases. A single administration of (225)Ac (400 nCi)-labeled anti-rat HER-2/neu monoclonal antibody (7.16.4) completely eradicated breast cancer lung micrometastases in approximately 67% of HER-2/neu transgenic mice and led to long-term survival of these mice for up to 1 year. Treatment with (225)Ac-7.16.4 is significantly more effective than (213)Bi-7.16.4 (120 muCi; median survival, 61 days; P = 0.001) and (90)Y-7.16.4 (120 muCi; median survival, 50 days; P < 0.001) as well as untreated control (median survival, 41 days; P < 0.0001). Dosimetric analysis showed that (225)Ac-treated metastases received a total dose of 9.6 Gy, significantly higher than 2.0 Gy from (213)Bi and 2.4 Gy from (90)Y. Biodistribution studies revealed that (225)Ac daughters, (221)Fr and (213)Bi, accumulated in kidneys and probably contributed to the long-term renal toxicity observed in surviving mice. These data suggest (225)Ac-labeled anti-HER-2/neu monoclonal antibody could significantly prolong survival in HER-2/neu-positive metastatic breast cancer patients. [Cancer Res 2009;69(23):8941-8].
PMID: 19920193
(remember, mice are short-lived)
perhaps giving a few treatments, followed by dialysis??Cancer Res. 2009 Nov 17. [Epub ahead of print]
Radioimmunotherapy of Breast Cancer Metastases with {alpha}-Particle Emitter 225Ac: Comparing Efficacy with 213Bi and 90Y.
Song H, Hobbs RF, Vajravelu R, Huso DL, Esaias C, Apostolidis C, Morgenstern A, Sgouros G.
Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, and Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland and Institute for Transuranium Elements, Karlsruhe, Germany.
alpha-Particles are suitable to treat cancer micrometastases because of their short range and very high linear energy transfer. alpha-Particle emitter (213)Bi-based radioimmunotherapy has shown efficacy in a variety of metastatic animal cancer models, such as breast, ovarian, and prostate cancers. Its clinical implementation, however, is challenging due to the limited supply of (225)Ac, high technical requirement to prepare radioimmunoconjugate with very short half-life (T(1/2) = 45.6 min) on site, and prohibitive cost. In this study, we investigated the efficacy of the alpha-particle emitter (225)Ac, parent of (213)Bi, in a mouse model of breast cancer metastases. A single administration of (225)Ac (400 nCi)-labeled anti-rat HER-2/neu monoclonal antibody (7.16.4) completely eradicated breast cancer lung micrometastases in approximately 67% of HER-2/neu transgenic mice and led to long-term survival of these mice for up to 1 year. Treatment with (225)Ac-7.16.4 is significantly more effective than (213)Bi-7.16.4 (120 muCi; median survival, 61 days; P = 0.001) and (90)Y-7.16.4 (120 muCi; median survival, 50 days; P < 0.001) as well as untreated control (median survival, 41 days; P < 0.0001). Dosimetric analysis showed that (225)Ac-treated metastases received a total dose of 9.6 Gy, significantly higher than 2.0 Gy from (213)Bi and 2.4 Gy from (90)Y. Biodistribution studies revealed that (225)Ac daughters, (221)Fr and (213)Bi, accumulated in kidneys and probably contributed to the long-term renal toxicity observed in surviving mice. These data suggest (225)Ac-labeled anti-HER-2/neu monoclonal antibody could significantly prolong survival in HER-2/neu-positive metastatic breast cancer patients. [Cancer Res 2009;69(23):8941-8].
PMID: 19920193