Phase I clinical trial of the humanized anti-EGF-r antibody H-R3 labeled with 99mTc in patients with tumor of epithelial origin

Aim: The aim of this study was to evaluate the biodistribution, internal radiation dosimetry, human anti-mouse antibody (HAMA) response and toxicity of the 99mTc labeled humanized H-R3 MAb using two dose levels. A preliminary analysis of the diagnostic efficacy was also performed. Material and methods: Twenty-five patients with suspicion of epithelial tumors were included on this study. They were divided in two groups. Group I (G-I): Ten patients received intravenous injection of 30mCi-3mg of 99mTc-H-R3; Group II (G-II): 15 patients received 60mCi-6mg of 99mTc-H-R3. Sequential Whole-Body, SPECT and planar images were acquired at different time intervals using a Sophy Camera DS7. Multiple blood and urine samples were collected up to 24 hours after injection. Hematological parameters and adverse effects were evaluated and classified using the WHO classification and HAMA response was also determined. Biodistribution was computed from the scintigraphic images using the Bio Dose software. The absorbed dose for 24 target organs and the equivalent and effective dose (EED, ED) were estimated using the Medical Internal Radiation Dosimetry (MIRD) Committee methodology. Data processing and statistic analyses were performed using the SPSS and microcal Origin v4.0 software packages. Results: Hepatic uptake showed the higher values: 50,7±6,4%ID (Teff = 2,9 hours) and 45.1±6, 25ID (Teff = 3.9 hours) in group I and II, respectively. Maximum uptakes in spleen and heart, for both group, were detected in the first image data-sets (1,6%ID and 2,5%ID respectively) and kidneys reaches the maximum value (1,9%ID) at 3 hours post-injection. The urinary bladder and large intestine had also a significant uptake due to the clearance pattern of this product. The mean urinary excretion was 22.2±7.6% up to 24 hours post-injection. The higher tumor uptake was estimated as 0.026%DI/g in a brain lesion. Liver received the higher absorbed doses (4,90E-02 mGy/MBq in G-I and 4,66E-02 mGy/MBq in G-II), followed by the kidneys and gallbladder wall. The maximum EED and ED were 0,0190mSv/MBq and 0,0143mSv/MBq, respectively. Biodistribution and dosimetric results did not show significant differences (p<0.05) between G-I and G-II. There were not hematological nor biochemical abnormalities with clinical significance related to the product. Only two patients showed mild and moderate adverse effects (chills and acute rhinitis), solved during the studies. No patient developed HAMA response. Preliminary analysis of clinical results showed a sensitivity of 76.5% and an specificity of 100%. Conclusions: The results of this study suggest that 99mTc-H-R3 can be used in patients in a safe and effective way for the diagnosis of epithelial cancer in the two evaluated dose levels