A comparison of the behavior of (64)Cu-acetate and (64)Cu-ATSM in vitro and in vivo

摘要: (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazonate), (64)Cu-ATSM, continues to be investigated clinically as a PET agent both for delineation of tumor hypoxia and an effective indicator patient prognosis, but there are still aspects the mechanism action that not fully understood.The retention radioactivity in tumors after administration (64)Cu-ATSM vivo is substantially higher with significant hypoxic fraction. This hypoxia-dependent believed involve reduction Cu-ATSM, followed by loss copper cellular processing. To shed light on possible role metabolism targeting, we have compared (64)Cu vitro CaNT EMT6 cells or cancers (64)Cu-acetate.In mice bearing tumors, biodistributions dynamic data broadly similar (64)Cu-acetate. Copper at 15 min injection (64)Cu-acetate than values result 2 16 h both. Colocalization measured EF5 immunohistochemistry evident h. Interestingly, although colocalizing hypoxia, reduced amounts increased oxygenation due inhalation O2. In vitro, less uptake observed (64)Cu-acetate, this had some selectivity. Although stable mouse serum alone, rapid disappearance intact complex from blood comparable bound activity (64)Cu-acetate.That vivo, studied, distribution radiocopper essentially mirrors suggests may also play selectivity Cu-ATSM.