title: Dosimetric analysis of 177Lu-cG250 radioimmunotherapy in renal cell carcinoma patients: correlation with myelotoxicity and pretherapeutic absorbed dose predictions based on 111In-cG250 imaging.
abstract: This study aimed to estimate the radiation absorbed doses to normal tissues and tumor lesions during radioimmunotherapy with (177)Lu-cG250. Serial planar scintigrams after injection of (111)In-cG250 or (177)Lu-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 (111)In-cG250 data, were determined.
  
  
  METHODS
  Twenty patients received a diagnostic tracer activity of (111)In-cG250 (185 MBq), followed by radioimmunotherapy with (177)Lu-cG250. The administered activity of (177)Lu-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 (111)In-cG250 data were used to simulate (177)Lu and (90)Y 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 (177)Lu-cG250, simulated (177)Lu-cG250, and simulated (90)Y-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 (177)Lu-cG250 data. Absorbed doses (whole body and red marrow) based on the simulated (177)Lu-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 (177)Lu-cG250 than for radioimmunotherapy with (90)Y-cG250, indicating that (177)Lu has a wider therapeutic window for radioimmunotherapy with cG250 than (90)Y.
  
  
  CONCLUSIONS
  In patients with metastasized renal cell carcinoma, hematologic toxicity after treatment with (177)Lu-cG250 can be predicted on the basis of administered activity and whole-body and red marrow-absorbed dose. Diagnostic (111)In-cG250 data can be used to accurately predict absorbed doses and myelotoxicity of radioimmunotherapy with (177)Lu-cG250. These estimations indicate that in these patients, higher radiation doses can be guided to the tumors with (177)Lu-cG250 than with (90)Y-cG250.
authors.affiliation: Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Stillebroer
authors.forename: Catharina M L
authors.initials: CM
authors.lastname: Zegers
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.forename: Joseph A
authors.initials: JA
authors.lastname: O'Donoghue
authors.forename: Eric P
authors.initials: EP
authors.lastname: Visser
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001610:Beta Particles / Q000009:adverse effects / Q000627:therapeutic use; D001853:Bone Marrow / Q000528:radiation effects*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D007680:Kidney Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D008187:Lutetium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011829:Radiation Dosage; D016499:Radioimmunotherapy / Q000379:methods*; D011874:Radiometry; D011877:Radionuclide Imaging; D011879:Radiotherapy Dosage
chemical_list: D000911:Antibodies, Monoclonal; C106533:G250 monoclonal antibody; D007205:Indium Radioisotopes; D008187:Lutetium