α-Radioimmunotherapy of Intraperitoneally Growing OVCAR-3 Tumors of Variable Dimensions: Outcome Related to Measured Tumor Size and Mean Absorbed Dose

Journal of Nuclear Medicine

Ingela Claesson¹  Jörgen Elgqvist¹  Stig Palm¹  Tom Bäck¹  Bengt R. Johansson¹  Holger Jensen¹  Ragnar Hultborn¹  Håkan Andersson¹  Marita Olsson¹  Sture Lindegren¹  Elisabet Warnhammar¹  Lars Jacobsson¹ 

关键词: ovarian cancer;    radioimmunotherapy;    dosimetry;    astatine;    MX35;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The purpose of this work was to (a) investigate the efficacy of radioimmunotherapy using 211At-MX35 F(ab′)2 or 211At-Rituximab F(ab′)2 (nonspecific antibody) against differently advanced ovarian cancer in mice; (b) image the tumor growth on the peritoneum; and (c) calculate the specific energy and mean absorbed dose to tumors and critical organs. Methods: Two experiments with 5-wk-old nude mice (n = 100 + 93), intraperitoneally inoculated with ∼1 × 107 NIH:OVCAR-3 cells, were done. At either 1, 3, 4, 5, or 7 wk after inoculation animals were intraperitoneally treated with ∼400 kBq 211At-MX35 F(ab′)2 (n = 50 + 45), ∼400 kBq 211At-Rituximab F(ab′)2 (n = 25 + 24), or unlabeled Rituximab F(ab′)2 (n = 25 + 24). At the time of treatment 29 animals were sacrificed and biopsies were taken for determination of tumor sizes using scanning electron microscopy (SEM). Eight weeks after each treatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. The specific energy and mean absorbed dose to tumors were calculated. The activity concentration was measured in critical organs and abdominal fluid. Results: When given treatment 1, 3, 4, 5, or 7 wk after cell inoculation the tumor-free fraction (TFF) was 95%, 68%, 58%, 47%, 26%, and 100%, 80%, 20%, 20%, and 0% when treated with 211At-MX35 F(ab′)2 or 211At-Rituximab F(ab′)2, respectively. The SEM images revealed maximum tumor radius of ∼30 μm 1 wk after cell inoculation, increasing to ∼340 μm at 7 wk. Specific energy to cell nuclei varied between 0 and ∼540 Gy, depending on assumptions regarding activity distribution and tumor size. The mean absorbed dose to thyroid, kidneys, and bone marrow was ∼35, ∼4, and ∼0.3 Gy, respectively. Conclusion: Treatment with 211At-MX35 F(ab′)2 or 211At-Rituximab F(ab′)2 resulted in a TFF of 95%−100% when the tumor radius was ≤30 μm. The TFF was decreased (TFF ≤ 20%) for 211At-Rituximab F(ab′)2 when the tumor radius exceeded the range of the α-particles. The specific antibody gave for these tumor sizes a significantly better TFF, explained by a high mean absorbed dose (>22 Gy) from the activity bound to the tumor surface and probably some contribution from penetrating activity.

【 授权许可】

Unknown