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Published on: January 18, 2019
Localization of monoclonal antibody TNT-1 in experimental kidney infarction of the mouse
F M Chen1, J R Wisner, H Omachi
1Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033.
Abstract:
An experimental kidney infarction model was developed in the mouse to study the uptake of a radiolabeled monoclonal antibody previously shown to bind to degenerating cells in malignant tumors. To determine if this approach is applicable to normal tissue and cell degeneration, kidney infarction was produced by clamping the mouse renal artery for 3 h using surgical procedures. Various groups of mice were injected with 131I-labeled TNT-1 F(ab')2 monoclonal antibody directed against nuclear histone antigens at varying intervals after surgery. Imaging, biodistribution, autoradiography, and histological studies were performed on each group of mice, including sham-operated controls, to quantitate the level of binding and localize the uptake of label in clamped and unclamped (contralateral) kidneys. As additional controls, clamped mice were administered radiolabeled irrelevant monoclonal antibody Lym-1 or mouse albumin. The results showed a marked selective uptake of radiolabeled TNT-1 F(ab')2 in the injured clamped kidney compared with the untreated kidney and other normal organs of the mouse. These studies define a model of normal organ necrosis that may be useful for study of the kinetics of antibody uptake in infarcted tissues.
Insights
Researchers developed a mouse kidney infarction model to study radiolabeled antibody uptake in degenerating normal tissue. The TNT-1 antibody selectively targeted injured kidney tissue, demonstrating potential for imaging infarcted organs.
Area of Science:
- Medical Imaging
- Nephrology
- Immunology
Background:
- Monoclonal antibodies targeting degenerating cells show promise in cancer research.
- Investigating antibody uptake in normal tissue degeneration is crucial for broader applications.
- A reliable model for studying normal organ necrosis is needed.
Purpose of the Study:
- To establish a mouse model of kidney infarction.
- To evaluate the uptake of a radiolabeled monoclonal antibody (131I-labeled TNT-1 F(ab')2) in infarcted kidney tissue.
- To assess the applicability of this antibody for imaging normal tissue degeneration.
Main Methods:
- Surgical induction of kidney infarction in mice by clamping the renal artery.
- Injection of 131I-labeled TNT-1 F(ab')2 antibody at varying intervals post-infarction.
- Control groups included sham-operated mice, irrelevant antibody (Lym-1), and mouse albumin.
- Quantitative analysis using imaging, biodistribution, autoradiography, and histology.
Main Results:
- Significant and selective uptake of 131I-labeled TNT-1 F(ab')2 was observed in the infarcted (clamped) kidney.
- Minimal uptake was detected in the contralateral (untreated) kidney and other normal organs.
- Control antibodies and albumin showed no specific accumulation in the injured kidney.
Conclusions:
- The developed mouse kidney infarction model effectively demonstrates selective antibody uptake in normal organ necrosis.
- The TNT-1 antibody shows potential for targeted imaging and study of infarcted tissues.
- This model serves as a valuable tool for investigating antibody kinetics in degenerating normal organs.

