Gallium-68-Labeled Anti-HER2 Single-Chain Fv Fragment: Development and In Vivo Monitoring of HER2 Expression

Purpose: We aimed to develop a gallium-68 (Ga-68)-labeled single-chain variable fragment (scFv) targeting the human epidermal growth factor receptor 2 (HER2) to rapidly and noninvasively evaluate the status of HER2 expression.Procedures: Anti-HER2 scFv was labeled with Ga-68 by using deferoxamine (Df) as a bifunctional chelate. Biodistribution of [⁶⁸Ga]Df-anti-HER2 scFv was examined with tumor-bearing mice and positron emission tomography (PET) imaging was performed. The changes in HER2 expression after anti-HER2 therapy were monitored by PET imaging.Results: [⁶⁸Ga]Df-anti-HER2 scFv was obtained with high radiochemical yield after only a 5-min reaction at room temperature. The probe showed high accumulation in HER2-positive xenografts and the intratumoral distribution of radioactivity coincided with HER2-positive regions. Furthermore, [⁶⁸Ga]Df-anti-HER2 scFv helped visualize HER2-positive xenografts and monitor the changes in HER2 expression after anti-HER2 therapy.Conclusion: [⁶⁸Ga]Df-anti-HER2 scFv could be a promising probe to evaluate HER2 status by in vivo PET imaging, unless trastuzumab is prescribed as part of the therapy.