Brief intraperitoneal radioimmunotherapy of small peritoneal carcinomatosis using high activities of noninternalizing 125I-labeled monoclonal antibodies

摘要

We assessed the efficiency and toxicity of brief-intraperitoneal radioimmunotherapy (Bip-RIT) using high activities of ¹²⁵I-labeled monoclonal antibodies (mAbs) in the treatment of small volume peritoneal carcinomatosis.MethodsFor Bip-RIT, athymic nude mice with peritoneal tumor xenografts were i.p. injected at day 4 post-graft with 185 MBq of ¹²⁵I-35A7 (anti-CEA mAb) (740 MBq/mg) and, after one hour, the peritoneal cavity was abundantly washed with saline solution to remove unbound radioactivity (Bip-¹²⁵I-35A7-RIT). Another group of mice received Bip-RIT and one intravenous (iv) injection of 37 MBq of ¹²⁵I-35A7 at day 7 or 11 after graft (Bip+ivd7- or Bip+ivd11-¹²⁵I-35A7-RIT). Control groups were treated with saline solution (Bip-NaCl) or with the irrelevant PX mAb (Bip+ivd7-¹²⁵I-PX-RIT). Tumor growth was followed by bioluminescence and SPECT-CT imaging and hematological toxicity evaluated by complete blood count. Survival time was reported and mice were sacrificed when the bioluminescence signal reached 4.5×10⁷ photons/s. The biodistribution of ¹²⁵I-35A7 mAbs after iv- or Bip-RIT was assessed and the mean absorbed irradiation dose by organs and tumors was calculated using the MIRD formalism.