Radioimmunotherapy with [131I]cG250 in patients with metastasized renal cell cancer: dosimetric analysis and immunologic response.
OBJECTIVE
A study was designed to define the therapeutic efficacy, safety, and toxicity of two sequential high-dose treatments of radioimmunotherapy with [131I]cG250 in patients with metastasized renal cell carcinoma. Here, we report the dosimetric analysis and the relationship between the development of a human antichimeric antibody response and altered pharmacokinetics.


METHODS
Patients (n = 29) with progressive metastatic renal cell carcinoma received a low dose (222 MBq) of [131I]cG250 for dosimetric analysis, followed by the first radioimmunotherapy with 2,220 MBq/m2 [131I]cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low dose of [131I]cG250 (n = 20) was given 3 months later. Provided that no accelerated blood clearance was observed, a second radioimmunotherapy of [131I]cG250 was administered at an activity-dose level of 1,110 MBq/m2 (n = 3) or 1,665 MBq/m2 (n = 16). After each administration, whole-body images were obtained and the pharmacokinetics and the development of human antichimeric antibody responses were determined. Radiation-absorbed doses were calculated for whole body, red marrow, organs, and metastases.


RESULTS
No correlation was found between hematologic toxicity and radiation-absorbed dose to the whole body or bone marrow, nor administered activity (MBq and MBq/kg). The tumor-absorbed doses varied largely. An inverse relation between tumor size and radiation-absorbed dose was found. Most tumor lesions received <10 Gy, whereas only lesions <5 g absorbed >50 Gy. A relatively high number of patients developed a human antichimeric antibody response (8 of 27) with altered pharmacokinetics, hampering additional radioimmunotherapies in four of these patients.


CONCLUSIONS
Dosimetric analysis did not adequately predict the degree of bone marrow toxicity. When human antichimeric antibody developed, the rapid clearance of radioactivity from the blood and body prohibited further treatment. According to the calculated absorbed dose in metastatic lesions, future radioimmunotherapy studies with radiolabeled cG250 should aim at treatment of small-volume disease or treatment in an adjuvant setting.
Brouwers
Adrienne H
AH
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. a.h.brouwers@nucl.umcg.nl
Buijs
Wilhelmina C A M
WC
Mulders
Peter F A
PF
de Mulder
Pieter H M
PH
van den Broek
Wim J M
WJ
Mala
Carola
C
Oosterwijk
Egbert
E
Boerman
Otto C
OC
Corstens
Frans H M
FH
Oyen
Wim J G
WJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D018450:Disease Progression; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016499:Radioimmunotherapy / Q000379:methods*; D011874:Radiometry; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D000911:Antibodies, Monoclonal; C106533:G250 monoclonal antibody; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins