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Updated: Aug 9, 2026
In Vivo Immunofluorescence Localization for Assessment of Therapeutic and Diagnostic Antibody Biodistribution in Cancer Research
Published on: September 16, 2019
Low and high tenascin-expressing tumors are efficiently targeted by ST2146 monoclonal antibody
Rita De Santis1, Claudio Albertoni, Fiorella Petronzelli
1Sigma-Tau SpA, R&D, Rome, Italy. rita.desantis@sigma-tau.it
Abstract:
ST2146biot is a biotinylated anti-tenascin monoclonal antibody (mAb) to be used for Pretargeted Antibody Guided Radioimmunotherapy (PAGRIT) of solid tumors. In vivo biodistribution studies of (125)I-labeled ST2146biot were done in nude mice transplanted with human HT-29 colon carcinoma and/or human U-118MG glioblastoma cells characterized for low and high tenascin expression, respectively. In vitro results show that ST2146 retains immunoreactivity upon biotinylation, in contrast to other anti-tenascin mAbs. In vivo biodistribution of ST2146 shows specific tumor accumulation up to 10 days after the i.v. injection, with no relevant differences between biotinylated and nonbiotinylated ST2146. A dose of 4 microg/mouse saturates the low tenascin-expressing human colon carcinoma HT-29, whereas the high tenascin-expressing human glioblastoma U-118MG seems to be saturated at a ST2146biot dose between 320 and 640 microg/mouse. The percentage of injected dose per gram of tumor ranges from 10% to 30%, corresponding to an amount of ST2146biot/g of tumor of approximately 400 ng/g and >200 microg/g for HT-29 and U-118MG, respectively. Tumor to normal organs uptake ratios are between 15 and 60, confirming high tumor selectivity of ST2146biot despite its cross-reactivity with the tenascin expressed at low level in the normal mouse organs. The ST2146biot localization data are substantially confirmed even when both low and high tenascin-expressing tumors are implanted in the same animal. To our knowledge, the absolute amount of ST2146biot, specifically localized in xenotransplanted human tumors, is the highest thus far described and supports the clinical use of this mAb in PAGRIT(R).
Insights
This study shows biotinylated ST2146 monoclonal antibody (mAb) effectively targets tenascin in solid tumors for radioimmunotherapy. It achieves high tumor accumulation and selectivity, supporting its clinical use in Pretargeted Antibody Guided Radioimmunotherapy (PAGRIT).
Area of Science:
- Oncology
- Immunology
- Radiochemistry
Background:
- Tenascin is a tumor-associated protein, making it a target for cancer therapies.
- Biotinylated antibodies can be used in Pretargeted Antibody Guided Radioimmunotherapy (PAGRIT) for enhanced tumor targeting.
- Previous anti-tenascin antibodies have shown limitations in immunoreactivity after biotinylation.
Purpose of the Study:
- To evaluate the in vitro immunoreactivity and in vivo biodistribution of biotinylated ST2146 monoclonal antibody (mAb).
- To assess the tumor targeting capabilities and dose saturation of ST2146biot in xenograft models with varying tenascin expression.
- To determine the potential of ST2146biot for use in Pretargeted Antibody Guided Radioimmunotherapy (PAGRIT) of solid tumors.
Main Methods:
- In vitro assessment of ST2146biot immunoreactivity post-biotinylation.
- In vivo biodistribution studies using (125)I-labeled ST2146biot in nude mice bearing human colon carcinoma (HT-29) and glioblastoma (U-118MG) xenografts.
- Evaluation of tumor uptake, saturation doses, and tumor-to-normal organ ratios.
Main Results:
- ST2146biot retained immunoreactivity after biotinylation, unlike other anti-tenascin mAbs.
- Specific and prolonged tumor accumulation of ST2146biot was observed (up to 10 days) with high tumor-to-normal organ ratios (15-60).
- Dose saturation varied, with 4 µg/mouse for HT-29 and 320-640 µg/mouse for U-118MG, demonstrating significant tumor localization.
Conclusions:
- Biotinylated ST2146 (ST2146biot) demonstrates excellent immunoreactivity and tumor targeting capabilities.
- The antibody shows high tumor selectivity and significant accumulation in xenotransplanted human tumors.
- These findings strongly support the clinical application of ST2146biot in Pretargeted Antibody Guided Radioimmunotherapy (PAGRIT).
