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Biodistribution and internal dosimetry of the 188Re-labelled humanized monoclonal antibody anti-epidemal growth factor receptor, nimotuzumab, in the locoregional treatment of malignant gliomas

2008; Lippincott Williams & Wilkins; Volume: 29; Issue: 1 Linguagem: Inglês

10.1097/mnm.0b013e3282f1bbce

1473-5628

Leonel Torres, Marco A. Coca, Juan F. Batista, Á. Casacó, G. López, Iván García, Alejandro Perera, Yamilé Peña, Abel Hernández, Yolaine Sanchez, Susana Romero, René Leyva, Anaís Prats, R. Palma Fernández,

Medical Imaging Techniques and Applications

Objective To evaluate the biodistribution, internal radiation dosimetry and safety of the 188Re-labelled humanized monoclonal antibody nimotuzumab in the locoregional treatment of malignant gliomas. Methods Single doses of 370 or 555 MBq of 188Re-labelled nimotuzumab were locoregionally administered to nine patients with recurrent high-grade gliomas, according to an approved dose-escalation study. SPECT, planar scintigraphy and magnetic resonance images were combined for dosimetric and pharmacokinetic studies. Blood and urine samples were collected to evaluate clinical laboratory parameters and for absorbed doses calculations. Biodistribution, internal dosimetry, human anti-mouse antibody response and toxicity were evaluated and reported. Results The 188Re-nimotuzumab showed a high retention in the surgically created resection cavity with a mean value of 85.5±10.3%ID 1 h post-injection. It produced mean absorbed doses in the tumour region of approximately 24.1±2.9 Gy in group I (patients receiving 370 MBq) and 31.1±6.4 Gy in group II (patients receiving 555 MBq); the normal organs receiving the highest absorbed doses were the kidneys, liver and urinary bladder. About 6.2±0.8%ID was excreted by the urinary pathway. The maximum tolerated dose was 370 MBq because two patients showed severe adverse effects after they received 555 MBq of 188Re-nimotuzumab. No patient developed human anti-mouse antibody response. Conclusions A locoregional single dose of 188Re-labelled nimotuzumab of approximately 370 MBq could be used safely in the routine treatment of patients suffering with high-grade gliomas. The efficacy of this therapy needs to be evaluated in a phase II clinical trial.