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Updated: May 19, 2026
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
(177)Lu/ (90)Y intermediate-affinity monoclonal antibodies targeting EGFR and HER2/c-neu: preparation and preclinical
Denis R Beckford Vera1, Sebastian Eigner, Katerina Eigner Henke
1Department of Radiopharmaceuticals, Academy of Sciences of the Czech Republic, Prague, Czech Republic. denis.beckford@gmail.com
Abstract:
The epidermal growth factor receptor (EGFR) is a rational target of anticancer therapies due to its overexpression in a variety of malignant epithelial tumors. Nevertheless, this antigen is also present in normal tissues. Consequently, monoclonal antibodies which selectively bind to EGFR-overexpressing tumors will be choice drug candidates for development of radioimmunoconjugates (RIC). Nimotuzumab (h-R3) and trastuzumab are monoclonal antibodies (mAbs) which would preferentially target tissues with EGFR and HER2 overexpression, respectively. In this chapter, we describe preparation and evaluation of the targeting properties of RIC formed by (177)Lu/(90)Y and monoclonal antibodies which selectively target EGFR- and HER2/c-neu-overexpressing tissues. mAbs were labeled with n.c.a. (177)Lu/(90)Y using bifunctional chelating agents. RIC binding properties and toxicity were evaluated in vitro using cell lines with varying antigen expression. In vivo tumor targeting properties of RIC were evaluated in mice bearing colorectal (SNU-C2B) and A431 tumor xenografts. RICs were prepared with specific activities up to 2 GBq/mg without significant loss in biological activity. (90)Y-h-R3/trastuzumab increased cell growth inhibition compared with unmodified mAbs or (90)YCl(3) alone in cell lines with overexpression of the target antigen. (177)Lu-h-R3 showed significantly higher uptake in A431 (22.8 ± 3.1% ID/g) than in SNU-C2B (8.8 ± 4.1% ID/g) xenografts at 72 h post injection, indicating strong association between tumor uptake and EGFR expression levels.
Insights
Radioimmunoconjugates (RIC) targeting epidermal growth factor receptor (EGFR) and HER2 show promise for cancer therapy. These RICs demonstrate effective tumor targeting and enhanced cell growth inhibition in preclinical models.
Area of Science:
- Oncology
- Radiopharmaceutical Chemistry
- Immunotherapy
Background:
- Epidermal growth factor receptor (EGFR) is overexpressed in many epithelial cancers, making it a target for anticancer therapies.
- Monoclonal antibodies (mAbs) targeting EGFR and HER2 are being developed for radioimmunoconjugates (RICs) to selectively target tumors.
- EGFR and HER2 are also present in normal tissues, necessitating careful selection of mAbs for targeted therapies.
Purpose of the Study:
- To prepare and evaluate radioimmunoconjugates (RICs) using lutetium-177 ((177)Lu) or yttrium-90 ((90)Y) labeled monoclonal antibodies (mAbs) targeting EGFR and HER2/c-neu.
- To assess the in vitro binding properties and toxicity of these RICs in cell lines with varying antigen expression.
- To evaluate the in vivo tumor targeting efficacy of the RICs in mouse models bearing colorectal and A431 tumor xenografts.
Main Methods:
- Monoclonal antibodies nimotuzumab (h-R3) and trastuzumab were labeled with non-carrier-added (177)Lu or (90)Y using bifunctional chelating agents.
- In vitro studies assessed RIC binding and toxicity using cancer cell lines with differential EGFR and HER2 expression.
- In vivo studies evaluated tumor targeting of RICs in mice bearing human colorectal (SNU-C2B) and A431 tumor xenografts.
Main Results:
- RICs were successfully prepared with high specific activities (up to 2 GBq/mg) without loss of biological activity.
- (90)Y-labeled h-R3/trastuzumab demonstrated increased cancer cell growth inhibition compared to unmodified mAbs or (90)YCl(3) alone in antigen-overexpressing cell lines.
- (177)Lu-h-R3 exhibited significantly higher uptake in EGFR-expressing A431 xenografts (22.8 ± 3.1% ID/g) compared to SNU-C2B xenografts (8.8 ± 4.1% ID/g) at 72 hours post-injection.
Conclusions:
- Radioimmunoconjugates targeting EGFR and HER2 can be effectively prepared and retain biological activity.
- RICs show promise for targeted cancer therapy, with tumor uptake correlating with antigen expression levels.
- These findings support the potential of (177)Lu/(90)Y-labeled mAbs as targeted radiotherapeutics for EGFR- and HER2-expressing malignancies.
