Targeting and therapy of human glioma xenografts in vivo utilizing radiolabeled antibodies
- Johns Hopkins Oncology Center, Baltimore, MD (USA)
Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. IIIIn-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCi of tumor activity/g/100 microCi injected activity compared to 4.5 microCi following administration of 100 microCi radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate the deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The dose found in normal organs is less than 20% of that in the tumor, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, demonstrates positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. To test the therapeutic potential of 90Y-radiolabeled P96.5 and ZME018, tumors and normal sites were implanted with miniature thermoluminescent dosimeters. Average absorbed doses of 3770 +/- 445 (SEM) and 645 +/- 48 cGy in tumor, 353 +/- 41 and 222 +/- 13 cGy in a contralateral control i.m. site, 980 +/- 127 and 651 +/- 63 cGy in liver, and 275 +/- 14 and 256 +/- 18 cGy in total body were observed 7 days following administration of 100 microCi 90Y-radiolabeled P96.5 and ZME018, respectively. Calculations of absorbed dose by the medical internal radiation dose method confirmed thermoluminescent dosimeter absorbed dose measurements.
- OSTI ID:
- 6938668
- Journal Information:
- Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 50; ISSN 0008-5472; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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550604 -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DIAGNOSTIC USES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DOSEMETERS
DOSES
EXPERIMENTAL NEOPLASMS
GLIOMAS
GLOBULINS
HOURS LIVING RADIOISOTOPES
IMMUNOGLOBULINS
IMMUNOLOGY
IMMUNOTHERAPY
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LUMINESCENT DOSEMETERS
MAMMALS
MEASURING INSTRUMENTS
MEDICINE
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIATION DOSES
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
RADIOIMMUNOSCINTIGRAPHY
RADIOIMMUNOTHERAPY
RADIOISOTOPE SCANNING
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RODENTS
SCINTISCANNING
THERAPEUTIC USES
THERAPY
THERMOLUMINESCENT DOSEMETERS
TRACER TECHNIQUES
USES
VERTEBRATES
YTTRIUM 90
YTTRIUM ISOTOPES