High molecular mass radioimmunoconjugates are promising for intraperitoneal α-emitter immunotherapy due to prolonged retention in the peritoneum

Introduction: Therapeutic efficacy of intraperitoneal radioimmunotherapy is dependent on the time of retention of the radioimmunoconjugates within the peritoneal cavity. Therefore, the aim of this study was to investigate intraperitoneal retention of Fab, IgG and IgM radioimmunoconjugates. Methods: Female Balb/c mice were injected with ²¹³Bi- or ¹¹¹In-labeled IgM, IgG and recombinant Fab conjugates intraperitoneally or intravenously. At different time points after injection, whole body distribution of radionuclides was imaged using a gamma camera. Distribution of radionuclides in selected organs was determined via γ-counting after sacrifice. Biological half-lives of the conjugates were calculated from whole body activities. Results: After i.p. injection ²¹³Bi-Fab rapidly accumulated in the kidneys indicative of glomerular filtration and reabsorption. Accumulation of ²¹³Bi-IgG in the kidneys was significantly lower. ²¹³Bi-IgM showed a striking accumulation in the liver 180 min after i.p. injection. ¹¹¹In-IgG persisted in the circulation up to 72 h both after i.p. and i.v. injection. ¹¹¹In-IgM showed a continuous accumulation in the liver. Moreover, ¹¹¹In-IgM was significantly higher 24 h after i.v. injection than i.p. injection both in liver and spleen. These differences could be confirmed via scintigraphy. After injection of ¹¹¹In-IgG differences in scintigraphic images between i.v. and i.p. were clearly visible only at 3 h. Biological half lives were 24 h, 45 h and 165 h for ¹¹¹In-IgM, ¹¹¹In-Fab and ¹¹¹In-IgG, respectively. Conclusions: Retention of radioimmunoconjugates in the peritoneal cavity positively correlates with the molecular mass of the antibody. Therefore, IgM radioimmunoconjugates should be preferably used in radioimmunotherapy of free floating tumor cells and small tumor cell clusters in the ascites of the peritoneal cavity.