期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 35, 期 7, 页码 1272-1281出版社
SPRINGER
DOI: 10.1007/s00259-008-0775-4
关键词
sodium iodide symporter; prostate cancer; PSA promoter; gene therapy; At-211 therapy
资金
- NCI NIH HHS [CA91956] Funding Source: Medline
Purpose We reported recently the induction of selective iodide uptake in prostate cancer cells (LNCaP) by prostate-specific antigen (PSA) promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of I-131. In the current study, we studied the potential of the high-energy alpha-emitter At-211, also transported by NIS, as an alternative radionuclide after NIS gene transfer in tumors with limited therapeutic efficacy of I-131 due to rapid iodide efflux. Methods We investigated uptake and therapeutic efficacy of At-211 in LNCaP cells stably expressing NIS under the control of the PSA promoter (NP-1) in vitro and in vivo. Results NP-1 cells concentrated At-211 in a perchloratesensitive manner, which allowed a dramatic therapeutic effect in vitro. After intrapertoneal injection of At-211 (1 MBq), NP-1 tumors accumulated approximately 16% ID/g At-211 (effective half-life 4.6 h), which resulted in a tumor-absorbed dose of 1,580 +/- 345 mGy/MBq and a significant tumor volume reduction of up to 82 +/- 19%, while control tumors continued their growth exponentially. Conclusions A significant therapeutic effect of At-211 has been demonstrated in prostate cancer after PSA promoter-directed NIS gene transfer in vitro and in vivo suggesting a potential role for At-211 as an attractive alternative radioisotope for NIS-targeted radionuclide therapy, in particular in smaller tumors with limited radionuclide retention time.
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