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Technetium-99m-Labeled Anti-EGF-Receptor Antibody in Patients with Tumor of Epithelial Origin: I. Biodistribution and Dosimetry for Radioimmunotherapy

Centers of Molecular Immunology, Clinical Research and Medical-Surgical Research, Institute of Nephrology, Orthopedic Hospital Frank País, Havana, Cuba
Radiation Internal Dose Information Center, Oak Ridge, Tennessee

Correspondence: For correspondence or reprints contact: Normando Iznaga-Escobar, Center of Molecular Immunology, P.O. Box 16040, Havana, 11600, Cuba.

ABSTRACT

Accurate estimation of biodistribution and absorbed dose to normal organs and tumors is important for immunoscintigraphic studies and radioimmunotherapy treatment planning. Methods: Four patients (3 men, 1 woman; mean age 54.8 ± 9.2 yr; range 42–64 yr) were administered 3 mg of anti-human epidermal growth factor receptor (anti-hEGF-r) antibody (ior egf/r3), radiolabeled with ^99mTc activity of 39.5 ± 1.1 mCi (range 38.5 mCi–40.7 mCi) by intravenous bolus infusion. After administration, blood and urine samples were collected from three patients up to 24 hr after injection. Whole-body anterior and posterior scans were obtained at 5 min and 1,3,5 and 24 hr after injection. Using a computer program, regions of interest were drawn over the heart, liver, spleen, bladder and tumor to measure the activity in the source organs at each scanning time. Time-activity curves for each source organ were then fitted to monoexponential or biexponential functions by nonlinear least squares regression using the flexible polyhedrals method, which adequately fit our data with the correlation coefficient of 0.985 ± 0.013, and were integrated to determine organ residence times. The mean absorbed doses to the whole body and various normal organs were then estimated from residence times and from blood and urine samples using the methods developed by the Medical Internal Radiation Dose Committee. The effective dose equivalent and effective dose were calculated as prescribed in ICRP Publication Nos. 30 and 60. Results: Plasma disappearance curves of ^99mTc-labeled anti-hEGF-r antibody were best-fit by a two-compartment model in all patients with a distribution half-life (t_1/2) of 0.207 hr ± 0.059 hr (mean ± s.d., n = 3) and an elimination half-life (t_1/2ß) of 13.9 hr ± 2.2 hr. Among the various organs, significant accumulation of the radiolabeled antibody was found in the liver (48.5% ± 4.4%, mean ± s.d.), heart (3.50% ± 0.17%) and spleen (3.1% ± 1.8%) at 5 min postadministration. These values were reduced to 3.2% ± 0.4%, 0.1% ± 0.01% and 0.1% ± 0.1%, respectively, at 24 hr. Mean cumulative urinary excretion of ^99mTc-labeled anti-hEGF-r antibody was 4.6% ± 0.6% at 24 hr postinjection. Estimates of radiation absorbed dose to normal organs in rad/mCi administered (mean ± s.d., n = 4) were: whole body 0.017 ± 0.002; gallbladder wall 0.074 ± 0.007; spleen 0.136 ± 0.076; and liver 0.267 ± 0.036. The effective dose equivalent and effective dose estimates for adults were 0.041 ± 0.008 rem/mCi and 0.027 ± 0.004 rem/mCi administered. Conclusion: This feasibility study indicates that ^99mTc-labeled anti-hEGF-r antibody (ior egf/r3) can be used safely; this analysis provides a dosimetric framework for future studies. This monoclonal antibody, labeled with ¹⁸⁸Re, could possibly permit a successful regional radioimmunotherapy of tumors of epithelial origin.

Key Words: biodistribution • dosimetry • radioimmunotherapy • human epidermal growth factor

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