A phase I study of 99mTc-hR3 (DiaCIM®), a humanized immunoconjugate directed towards the epidermal growth factor receptor

A phase I trial was conducted to evaluate the safety, tumour and normal tissue localization, pharmacokinetics and radiation dosimetry of 99m Tc-hR3, a humanized monoclonal antibody directed towards the epidermal growth factor receptor, in 12 patients with recurrent or metastatic epithelial malignancies. Patients were injected intravenously with 3.0 mg or 6.0 mg (1010 MBq) of 99m Tc-hR3. Blood and plasma concentrations of radioactivity were measured and a complete 24 h urine collection was obtained. Whole-body images were acquired up to 24 h post-injection and normal organ uptake quantified. Radiation dosimetry was estimated using MIRDose. Safety was evaluated by clinical observation, biochemical/haematological testing and by measuring immune response to 99m Tc-hR3. There were no adverse effects, no changes in biochemical/haematological indices and no immune response to 99m Tc-hR3. 99m Tc-hR3 was rapidly cleared from the blood with a distribution half-life of 108±38 min. The volume of distribution, V d , and clearance, C, were 180±37 ml.kg -1 and 14±3 ml.kg -1 .min -1 , respectively. The elimination phase could not be discerned due to increasing blood radioactivity at later times. About 19-24% was excreted in the urine. Normal tissue uptake was mainly in the liver (44-50%), spleen (3-4%) and kidneys (3%). Imaging was positive in one patient with squamous cell carcinoma of the mouth and an involved cervical lymph node. The whole-body radiation dose from 99m Tc-hR3 was 1.34±0.02 × 10 -8 mSv.Bq -1 . We conclude that 99m Tc-hR3 exhibited an excellent safety profile. Future studies to determine the sensitivity and specificity of imaging with 99m Tc-hR3 in a larger group of patients with pre-selection for epidermal growth factor receptor positivity are planned.