Novel method for the detection of necrotic lesions in human cancers
Data are presented in support of the hypothesis that malignant tumors, containing abnormally permeable, degenerating cells, can be selectively detected using monoclonal antibodies to intracellular antigens. Biodistribution, imaging, and autoradiographic studies were performed in nude mice transplanted with four different human tumor cell lines to demonstrate the binding of radiolabeled antinuclear monoclonal antibodies within bulky tumors containing necrotic lesions. For these studies, two monoclonal antibodies, designated TNT-1 (IgG2a) and TNT-2 (IgM) were chosen since they were found to bind to abundant nuclear antigens which are retained in permeable, dying cells. F(ab')2 fragments prepared by pepsin digestion were radiolabeled with iodine-125 or iodine-131 by the iodogen method for i.v. administration. Biodistribution studies in nontumor-bearing BALB/c mice at various time intervals revealed normal patterns of antibody excretion with no accumulation of antibody in healthy organs. In contrast, biodistribution studies performed on Day 3 in tumor-bearing nude mice showed high tumor to organ ratios in those animals bearing necrotic tumors. Necrotic regions dissected at necropsy gave tumor to blood ratios as high as 131:1. Transplants having little demonstrable necrosis were found to have low tumor to blood ratios (0.4:1). Sequential imaging studies confirmed the high tumor-to-organ ratios and showed positive tumor imaging as early as 4 h. Autoradiographic studies of excised tumors showed the presence of label selectively in necrotic areas with preferential labeling over the nuclei of degenerating cells. Because of the universal presence of these nuclear antigens and the known prevalence of necrosis in tumors, this approach may be of value for the imaging and treatment of a wide variety of cancers in humans.
- Research Organization:
- Univ. of Southern California, Los Angeles (USA)
- OSTI ID:
- 6544165
- Journal Information:
- Cancer Res.; (United States), Vol. 48:20
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
MONOCLONAL ANTIBODIES
DIAGNOSTIC USES
AUTORADIOGRAPHY
BIOLOGICAL MODELS
EXPERIMENTAL NEOPLASMS
IMAGES
IODINE 125
IODINE 131
LABELLING
MICE
NECROSIS
TISSUE DISTRIBUTION
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
PATHOLOGICAL CHANGES
RADIOISOTOPES
RODENTS
USES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics