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

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.

Phase I/II clinical trial of the humanized anti-EGF-r monoclonal antibody h-R3 labelled with 99mTc in patients with tumour of epithelial origin.

AIM: To evaluate the biodistribution, internal radiation dosimetry and toxicity of the humanized MAb h-R3 labelled with Tc in humans. METHODS: Twenty-five patients with suspected epithelial-derived tumours were included in this study and divided into two groups: group I consisted of 10 patients who received 3 mg/1110 MBq (3 mg/30 mCi); and group II consisted of 15 patients who received 6 mg/2220 MBq (6 mg/60 mCi). Single photon emission computed tomography (SPECT) and planar images, and multiple blood and urine samples were collected up to 24 h after injection. Haematological parameters and adverse effects were classified according to the WHO criteria. Biodistribution, human anti-mouse antibody (HAMA) response and absorbed doses were estimated and reported. RESULTS: Liver, spleen, kidneys and heart were identified as source organs. Their higher uptakes were 53.3+/-6.4%ID, 2.0+/-1.4%ID, 9.8+/-4.3%ID and 2.8+/-0.9%ID, respectively. The urinary bladder and large intestine also had a significant uptake. The mean urinary excretion was around 22%ID. The liver received the highest absorbed doses followed by the kidneys and the urinary bladder wall. There were no haematological or biochemical abnormalities with clinical significance related to the product. No patient developed HAMA response. Preliminary analysis of clinical results showed a sensitivity of 76.5% and a specificity of 100%. CONCLUSIONS: The results of this study suggest that Tc-h-R3 could be used in patients in a safe and effective way, for the diagnosis of epithelial-derived tumours at the two evaluated dose levels.