Comparison of the targeting characteristics of various radioimmunoconjugates for radioimmunotherapy of neuroblastoma: Dosimetry calculations incorporating cross-organ beta doses


Ugur Ö., Kostakoglu L., Hui E., Fisher D., Garmestani K., Gansow O., ...More

NUCLEAR MEDICINE AND BIOLOGY, vol.23, no.1, pp.1-8, 1996 (SCI-Expanded) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 1
  • Publication Date: 1996
  • Doi Number: 10.1016/0969-8051(95)02001-2
  • Journal Name: NUCLEAR MEDICINE AND BIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED)
  • Page Numbers: pp.1-8
  • Keywords: radioimmunotherapy, radiation dosimetry, monoclonal antibody, neuroblastoma, GD2-SPECIFIC MONOCLONAL-ANTIBODY, COLON-CARCINOMA XENOGRAFTS, B-CELL LYMPHOMA, NUDE-MICE, TUMOR-LOCALIZATION, FRAGMENTS, THERAPY, CANCER, BIODISTRIBUTION, RADIONUCLIDES
  • Hacettepe University Affiliated: Yes

Abstract

To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combinations should be used to deliver the highest tumor and the lowest normal tissue doses. In a mouse model, tumor and critical organ-absorbed doses delivered by different radioimmunoconjugates were calculated and compared. We used a Medical Internal Radiation Dosimetry (MIRD)-style mouse dosimetry model that incorporates cross-organ beta doses to make refined estimates of the radiation absorbed dose to tissues. Biodistribution data from neuroblastoma xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed dose values for Y-90-3F8, I-131-3F8 and I-131-F(ab')(2) fragments. Immunoreactive fractions of the radiolabeled antibodies were comparable. Although tumor uptake of the radioiodinated and radiometal labeled 3F8 was much higher than that of the radioiodinated F(ab')(2) fragments (maximum percent injected dose per gram values were 39.4, 33.2 and 20.1 for I-131-3F8, Y-90-3F8 and I-131-F(ab')(2), respectively), tumor to nontumor ratios were higher for radioiodinated fragments (with the exception of tumor to kidney ratio). For the minimum tumor dose necessary for complete ablation, the bone marrow received 195, 278 and 401 cGy for I-131-F(ab')2, I-131-3F8 and Y-90/3F8, respectively. Tumor doses were 50.1, 232 and 992 cGy/MBq for I-131-F(ab')(2), I-131-3F8 and Y-90-3F8, respectively. Tumor to bone marrow dose, which is defined as the therapeutic index, was 21.5, 14.7 and 10.4 for I-131-F(ab')(2), I-131-3F8 and Y-90-3F8. I-131-F(ab')(2) fragments produced the highest therapeutic index but also the lowest tumor dose for radioimmunotherapy. Radiometal conjugated IgG produced the highest tumor dose but also the lowest therapeutic index.