ArticleEJNMMI research2025
Measurement of specific and nonspecific tissue uptake of antibodies in tumor by SPECT imaging and nonlinear compartmental modeling.
Article in EJNMMI research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Quantitative Mass Spectrometry-Based Biodistribution of Monoclonal Antibodies: An Alternative to Radio-Biodistribution.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Development of a Dual-Isotope Imaging Technique for Simultaneous Quantification and Evaluation of Biodistribution of Antibodies Using "XCam-CdTe".Pharmaceutical research · 2026Article
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Authors and funding
6 authors.
Funding
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Abstract
backgroundUnderstanding the mechanisms driving specific and nonspecific tissue uptake of antibodies can inform protein engineering strategies that maximize therapeutic efficacy in target tissues while minimizing off-target tissue toxicities. While in vitro cell assays are typically used to study these internalization mechanisms, there are few methods readily available to evaluate these pathways in vivo. Single photon emission computed tomography (SPECT) imaging with a non-residualizing radiohalogen probe can measure total levels of intact antibody, and a residualizing radiometal-chelate probe, in combination with a non-residualizing probe, can measure catabolized antibody associated with receptor-mediated and nonspecific internalization processes. Here, we describe a SPECT imaging study in human epidermal growth factor receptor 2 (HER2)-expressing tumor-bearing mice aimed at measuring whole body disposition kinetics of tumor-targeting trastuzumab (anti-HER2) and non-targeting (anti-gD) antibodies. Mice received these molecules labeled with either a non-residualizing prosthetic group ([
resultsSPECT imaging data confirmed significant HER2-mediated tumor uptake and catabolism of anti-HER2, evidenced by the high
conclusionHere, we successfully developed an imaging and modeling approach to capture anti-HER2 antibody receptor binding as well as specific and nonspecific internalization over time in vivo. These data and analyses demonstrate the power of SPECT imaging using both non-residualizing and residualizing radioisotopes to better characterize the different biological states (free, bound, and catabolized) of antibodies within interstitial and intracellular compartments. Understanding these distinct antibody internalization mechanisms in tumor and non-tumor tissues enables more informed decisions on dose selection to optimize treatment of tumors with heterogeneous antigen expression while minimizing nonspecific toxicities.
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