Dosimetric Analysis of 177Lu-cG250 Radioimmunotherapy in Renal Cell Carcinoma Patients: Correlation with Myelotoxicity and Pretherapeutic Absorbed Dose Predictions Based on 111In-cG250 Imaging

This study aimed to estimate the radiation absorbed doses to normal tissues and tumor lesions during radioimmunotherapy with Lu-177-cG250. Serial planar scintigrams after injection of In-111-cG250 or Lu-177-cG250 in patients with metastasized renal cell carcinoma were analyzed quantitatively. The estimated radiation doses were correlated with observed hematologic toxicity. In addition, the accuracy of the predicted therapeutic absorbed doses, based on diagnostic In-111-cG250 data, were determined. Methods: Twenty patients received a diagnostic tracer activity of In-111-cG250 (185 MBq), followed by radioimmunotherapy with Lu-177-cG250. The administered activity of Lu-177-cG250 was escalated by entering 3 patients at each activity level starting at 1,110 MBq/m(2), with increments of 370 MBq/m(2). After each diagnostic and therapeutic administration, whole-body scintigraphic images and pharmacokinetic data were acquired. Hematologic toxicity was graded using the Common Toxicity Criteria, version 3.0. Diagnostic In-111-cG250 data were used to simulate Lu-177 and Y-90 data by correcting for the difference in physical decay. Absorbed doses were calculated for the whole body, red marrow, organs, and tumor metastases for the therapeutic Lu-177-cG250, simulated Lu-177-cG250, and simulated Y-90-cG250 data. Results: Observed hematologic toxicity, especially platelet toxicity, correlated significantly with the administered activity (r = 0.85), whole-body absorbed dose (r = 0.65), and red marrow dose (r = 0.62 and 0.75). An inverse relationship between the mass and absorbed dose of the tumor lesions was observed. Calculated mean absorbed doses were similar for the simulated and measured Lu-177-cG250 data. Absorbed doses (whole body and red marrow) based on the simulated Lu-177-cG250 data correlated with the observed platelet toxicity (r = 0.65 and 0.82). The tumor-to-red marrow dose ratio was higher for radioimmunotherapy with Lu-177-cG250 than for radioimmunotherapy with Y-90-cG250, indicating that Lu-177 has a wider therapeutic window for radioimmunotherapy with cG250 than Y-90. Conclusion: In patients with metastasized renal cell carcinoma, hematologic toxicity after treatment with Lu-177-cG250 can be predicted on the basis of administered activity and whole-body and red marrow-absorbed dose. Diagnostic In-111-cG250 data can be used to accurately predict absorbed doses and myelotoxicity of radioimmunotherapy with Lu-177-cG250. These estimations indicate that in these patients, higher radiation doses can be guided to the tumors with Lu-177-cG250 than with Y-90-cG250.