Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours

Aim The aim of the study was to determine the equivalent total body dose (ETBD) using the cytokinesis blocked micronucleus assay in 22 I-131-meta-iodobenzylguanidine (I-131-MIBG) therapies (18 neuroblastoma, mean 5097 MBq, SD 1591; and four carcinoid tumours, mean 7681 MBq, SD 487). The results are correlated with the total body radiation dose according to the Medical internal Radiation Dosimetry (MIRD) formalism. Methods For each patient, blood samples were taken immediately before and 1 week after I-131-MIBG therapy. The first blood sample was irradiated in vitro with Co-60 gamma -rays to determine the dose-response curve. Micronuclei were scored in 1000 binucleated cells. By using the dose-response curve the ETBD was derived from the increase in micronuclei after I-131-MIBG therapy (second blood sample). Based on three consecutive biplanar scans taken at 3, 6 and 9 days post-administration respectively, the total body dose following the MIRD formalism was calculated. Results The micronucleus assay was evaluable in only 14 out of 22 I-131-MIBG therapies due to cell division inhibition caused by previous chemotherapy treatments and lymphocyte dilution due to blood transfusions given shortly after I-131-MIBG therapy. For these 14 therapies, the mean micronucleus yield after I-131-MIBG therapy was significantly increased (P < 0.01) with a mean of 92 (SD 77) for neuroblastoma patients and with a mean of 35 (SD 8) for carcinoid patients. The increase observed in the present study is greater than previously observed after I-131 therapy and Sr-89 therapy but much lower than after external beam radiotherapy. For all patients treated with multiple therapies, the initial increase in micronucleus yield had at least partially recovered by the time of the next therapy. This might be explained by an increased turnover of lymphocytes. A mean ETBD of 0.95 Gy (SD 0.55) for neuroblastoma patients and a mean of 0.46 Gy (SD 0.09) for carcinoid patients was calculated. A reasonable correlation (R=0.87) between the ETBD and the MIRD dose was obtained. The slope value of 0.75 can be explained by the low dose rate effect. Conclusions The observation in the present study of important inter-individual variability in the total body dose, with the possibility of high dose values, suggests the necessity of individual dosimetry when administering I-131-MIBG therapy, especially considering that generally more than one therapy is given to each patient. ((C) 2001 Lippincott Williams & Wilkins).