RADIATION ABSORBED DOSES AND SAFETY OF THE HUMANIZED MONOCLONAL ANTIBODY H-R3 LABELED WITH 99MTC Leonel A. Torres, Marco A. Coca, Maria E. Solano, Alejandro Perera, Juan F. Batista, Abel Hernandez, Tania Crombet, Marilyn Perez, Mayra Ramos, Elvia L Sanchez, Susana Romero, Vicente Aguilar, Normando Iznaga Centro de Investigaciones Clínicas Calle 34 #4501 esq. 45. Reparto Kohly, Playa, Havana, Cuba AP 11300 Telf.: (537) 23 0087 Fax: (537) 24 3298 E-mail: leonel@infomed.sld.cu ABSTRACT Introduction. Labeled humanized monoclonal antibodies (Mab) for the diagnosis and treatment of tumors using Nuclear Medicine procedures have contributed to decrease the immunogenicity and HAMA response of murine MAbs, increasing the effectiveness and usefulness of radioimmunoscintigraphic procedures. The objective of this study was to evaluate the internal radiation dosimetry and safety of the 99mTc-labeled H-R3 Mab, in humans. Material and methods: Ten patients with suspicions of epithelial tumors were included on this study. They received 1110 MBq of 99mTc H-R3, intravenously. Multiple blood, urine samples and sequential whole-body images were collected at different times. The internal radiation dosimetry was estimated using the Medical Internal Radiation Dosimetry (MIRD) Committee methodology. Biodistribution was computed from the scintigraphic images and regression analysis of the time- activity curves was employed to compute the residence times of the source organs. Hematological toxicity and adverse effects were evaluated using the WHO classification. Results: Liver received the higher absorbed dose (4,90E-02mGy/MBq), followed by the kidneys (1,60E-02mGy/MBq) and gallbladder wall (1,53E- 02mGy/MBq). The effective dose and the effective equivalent dose were 0,0143 mSv/MBq and 0,0190 mSv/MBq, respectively. The main source organs of this radiopharmaceutical were liver, spleen, kidneys and heart. No significant changes were observed in the hematological parameters and only two patients showed mild and moderate adverse effects, solved during the studies and not related with radiation exposures. Palabras clave: absorbed doses, monoclonal antibody, 99mTc. 1. INTRODUCTION. Almost 90% of malignancies are epithelial derived tumors. Cancer of epithelial origin constitutes one of the first causes of death world-wide [1]. Tumors of epithelial origin, like cancer of lung, digestive tract, breast and others, have an overexpression of the epidermal growth factor receptor (EGF-R) [2]. This fact is often related to malignancy and poor prognosis of the disease [3]. Clinical trials have shown that anti-EGF-R monoclonal antibodies (MAbs) could be useful for immunoscintigraphic diagnosis of epidermal tumours [4,5]. In order to decrease the immunogenicity and HAMA response to the murine MAbs, and increase the half-live of the molecule in the patient, it was developed a reshaped humanized monoclonal antibody H-R3. This study include the preliminary results of the internal radiation dosimetry, biodistribution and safety of the 99mTc-labelled H-R3 used for radioimmunodiagnosis of tumors of epithelial origin. 2. MATERIAL AND METHODS Antibody Labelling and Quality Control. Freeze-dried kits with 3 mg of humanised MAb H-R3 (Centre of Molecular Immunology, Havana, Cuba) were reconstituted with 1295 MBq of pertechnetate from a 99 Mo/ 99m Tc generator (CIS-BioInternational, France). Labelled product was subjected to ascending paper chromatography. Radiochemical purity higher 90% was considered satisfactory for patient’s administration. Studied Patients Ten adult patients (6 females and 4 males) were enrolled on this study. They received 3 mg of MAb labeled with 1110 MBq of 99mTc. All patients were suspected of having either primary or recurrent cancer of epithelial origin and had undergone CT scanning, x-ray and other determinations. Histopathological findings were considered as a confirmation criterion (gold standard). All studied patients gave their written informed consent previously to be included in the clinical trial. Biodistribution studies and internal radiation dosimetry analysis. Anterior and posterior whole body images were acquired at 5 min, 1 h, 3 h, 5 h and 24 h after administration of radiopharmaceutical, using a gamma camera (SOPHYCAMMERA DS7, France). The gamma camera head was fitted with a diverging parallel-hole collimator to increase the lateral viewing aspect. A 20% window centered on the 140 keV emission peak of the 99m Tc was employed. On the gantry movements were used a speed of 20 cm/min. All whole-body images were stored in the computer in 2048x512 byte mode matrix. All images were processed in a SOPHY-20P system using the software BioDose v1.0, developed at the Centre for Clinical Research. Geometric mean images were computed Memorias II Congreso Latinoamericano de Ingeniería Biomédica, Habana 2001, Mayo 23 al 25, 2001, La Habana, Cuba 950-7132-57-5 (c) 2001, Sociedad Cubana de Bioingeniería, artículo 00437