Radiolocalization of human small cell lung cancer and antigen-positive normal tissues using monoclonal antibody LS2D617
- Hybritech Inc., San Diego, CA (USA)
The murine monoclonal antibody LS2D617, which reacts with an antigen associated with human small cell lung carcinoma (SCLC), was tested in preclinical models to assess its potential for specific targeting of tumors in human SCLC cancer patients. LS2D617 detects a cell antigen on the surface of cultured SCLC and neuroblastoma cell lines. Scatchard analysis of the binding of LS2D617 to NCIH69 SCLC cells indicates an affinity constant of about 1 x 10(8) M-1 and an epitope expression level of approximately 2 x 10(6) antigenic sites/cell. Molecular weight analysis of the target antigen and antibody competition experiments showed that LS2D617 should be classified as a SCLC Cluster 1 antibody. LS2D617 was labeled with 111In and tested for biodistribution (4, 24, 48, 72, and 96 h postinjection) in nude mice bearing the human SCLC NCIH69 tumor. Tumor values peaked at about 35% injected dose/g (Day 3) compared with about 8% injected dose/g for an irrelevant IgG1 antibody while normal tissue accumulation for both antibodies was about 2-8% injected dose/g. Immunohistochemical studies demonstrated that LS2D617 reacts with the central nervous system, peripheral nerves, endocrine tissues, and heart tissue of rabbits as it does in human tissues. The ability of LS2D617 to accumulate in vivo in normal tissues that express the specific target antigen was tested in rabbits. Rabbits given i.v. injections of 111In-LS2D617 or control labeled antibody were sacrificed at 48 h and tissues were examined by gamma well counting, autoradiography, and immunohistochemical staining for murine immunoglobulin. Specific uptake was seen in all sites defined as antigen positive by immunohistology (i.e., heart, liver bile duct, peripheral nerves, pituitary, adrenal), except the central nervous system (brain and spinal cord) which was inaccessible to antibody because of the blood brain barrier.
- OSTI ID:
- 6809609
- Journal Information:
- Cancer Research; (USA), Vol. 50:10; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CARCINOMAS
DIAGNOSIS
LUNGS
RADIOIMMUNOSCINTIGRAPHY
MONOCLONAL ANTIBODIES
TISSUE DISTRIBUTION
ADHESION
ANTIGENS
AUTORADIOGRAPHY
BLOOD-BRAIN BARRIER
INDIUM 111
MAN
MICE
MOLECULAR WEIGHT
RABBITS
RADIATION DOSES
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BODY
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DISEASES
DISTRIBUTION
DOSES
ELECTRON CAPTURE RADIOISOTOPES
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MINUTES LIVING RADIOISOTOPES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANS
PRIMATES
RADIOIMMUNODETECTION
RADIOISOTOPE SCANNING
RADIOISOTOPES
RESPIRATORY SYSTEM
RODENTS
SCINTISCANNING
TRACER TECHNIQUES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics