Biodistribution and localization of radiolabeled NR-LU-10 fab fragment in human breast cancer xenografts

Radioimmunodetection, which takes advantage of tumor-specific or tumor-associated radiolabeled monoclonal antibodies or other biologic molecules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The difficulty is in findi...

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Veröffentlicht in:Nuclear medicine and biology 1998-10, Vol.25 (7), p.633-637
Hauptverfasser: Burak, William E, DePalatis, Louis, Nines, Ronald, Hitchcock, Charles, Hinkle, George, Houchens, David, Farrar, William B
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container_end_page 637
container_issue 7
container_start_page 633
container_title Nuclear medicine and biology
container_volume 25
creator Burak, William E
DePalatis, Louis
Nines, Ronald
Hitchcock, Charles
Hinkle, George
Houchens, David
Farrar, William B
description Radioimmunodetection, which takes advantage of tumor-specific or tumor-associated radiolabeled monoclonal antibodies or other biologic molecules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The difficulty is in finding an antibody that is both sensitive and specific enough to localize in breast tumors. This study undertook immunohistochemical and in vivo evaluation of tumor localization and biodistribution of NR-LU-10 Fab (antibody fragment) in breast tumors to determine its ability to bind selectively to malignant tissue. NR-LU-10 Fab recognizes a pancarcinoma glycoprotein antigen found on tumors of epithelial cell origin. NR-LU-10 Fab reacted with 6/6 (100%) breast cancer cell lines and 14/16 (87.5%) breast tumors with varying degrees of immunostaining intensities. Athymic mice bearing ZR-75-1 breast cancer xenografts were injected with 125I-labeled NR-LU-10 Fab (12 μg/5 μCi) and sacrificed at fixed time intervals. These studies demonstrated the highest tumor uptake of labeled Fab at 12 h postinjection (4.58 ± 1.59% of injected dose/gram [% ID/g] of tissue); this gradually decreased to 0.13 ± 0.05% ID/g of tissue by 72 h postinjection of the radiolabeled Fab. Biolocalization to normal tissues was as predicted for a Fab fragment; i.e., initially high in clearance organs (kidney), followed by rapid clearance over the 72-h test period. NR-LU-10 Fab displays adequate breast tumor localization with minimal biolocalization to normal tissues, thus supporting its potential use in radioimmunoscintigraphy and the RIGS® system (radioimmunoguided surgery).
doi_str_mv 10.1016/S0969-8051(98)00028-6
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Biolocalization to normal tissues was as predicted for a Fab fragment; i.e., initially high in clearance organs (kidney), followed by rapid clearance over the 72-h test period. NR-LU-10 Fab displays adequate breast tumor localization with minimal biolocalization to normal tissues, thus supporting its potential use in radioimmunoscintigraphy and the RIGS® system (radioimmunoguided surgery).</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>9804044</pmid><doi>10.1016/S0969-8051(98)00028-6</doi><tpages>5</tpages></addata></record>
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subjects Animals
Antibodies, Monoclonal - chemistry
Antibodies, Monoclonal - metabolism
Antibody Specificity
Biolocalization
Biological and medical sciences
Breast cancer
Breast Neoplasms - chemistry
Breast Neoplasms - diagnostic imaging
Breast Neoplasms - pathology
Disease Models, Animal
Endocrine glands. Genital system. Mammary gland
Female
Humans
Immunoglobulin Fab Fragments - chemistry
Immunoglobulin Fab Fragments - metabolism
Immunohistochemistry
Investigative techniques, diagnostic techniques (general aspects)
Lymphoma - chemistry
Lymphoma - diagnostic imaging
Lymphoma - pathology
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Transplantation
NR-LU-10 antibody
Radioimmunodetection - methods
Radionuclide investigations
Tissue Distribution - drug effects
Tumor Cells, Cultured
Xenografts
title Biodistribution and localization of radiolabeled NR-LU-10 fab fragment in human breast cancer xenografts
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