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HER3 PET Imaging: ⁶⁸Ga-Labeled Affibody Molecules Provide Superior HER3 Contrast to ⁸⁹Zr-Labeled Antibody and Antibody-Fragment-Based Tracers.

ABSTRACT: HER3 (human epidermal growth factor receptor type 3) is a challenging target for diagnostic radionuclide molecular imaging due to the relatively modest overexpression in tumors and substantial expression in healthy organs. In this study, we compared four HER3-targeting PET tracers based on different types of targeting molecules in a preclinical model: the ⁸⁹Zr-labeled therapeutic antibody seribantumab, a seribantumab-derived F(ab)₂-fragment labeled with ⁸⁹Zr and ⁶⁸Ga, and the ⁶⁸Ga-labeled affibody molecule [⁶⁸Ga]Ga-Z_HER3. The novel conjugates were radiolabeled and characterized in vitro using HER3-expressing BxPC-3 and DU145 human cancer cells. Biodistribution was studied using Balb/c nu/nu mice bearing BxPC-3 xenografts. HER3-negative RAMOS xenografts were used to demonstrate binding specificity in vivo. Autoradiography was conducted on the excised tumors. nanoPET/CT imaging was performed. New conjugates specifically bound to HER3 in vitro and in vivo. [⁶⁸Ga]Ga-DFO-seribantumab-F(ab')₂ was considered unsuitable for imaging due to the low stability and high uptake in normal organs. The highest tumor-to-non-tumor contrast with [⁸⁹Zr]Zr-DFO-seribantumab and [⁸⁹Zr]Zr-DFO-seribantumab-F(ab')₂ was achieved at 96 h and 48 h pi, respectively. Despite lower tumor uptake, [⁶⁸Ga]Ga-Z_HER3 provided the best imaging contrast due to the fastest clearance from blood and normal organs. The results of our study suggest that affibody-based tracers are more suitable for PET imaging of HER3 expression than antibody- and antibody-fragment-based tracers.

SUBMITTER: Rinne SS

PROVIDER: S-EPMC8508546 | biostudies-literature |

REPOSITORIES: biostudies-literature

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