PSMA-targeting hybrid molecule PSMA-914 for preoperative imaging and intraoperative fluorescence-guidance: A first-in-human experience

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• Picked for Urology (paper of the day, 7 August 2026): PSMA‑914 hybrid imaging for prostate cancer surgery guidance

Abstract

UNLABELLED: Surgery remains the cornerstone of prostate cancer treatment, demanding accurate tumor delineation and margin assessment. The hybrid molecule PSMA-914, which combines positron emission tomography (PET) and near-infrared fluorescence (NIRF) detection capabilities, was developed to improve preoperative imaging and intraoperative guidance during prostate cancer surgery. METHODS: In this first-in-human series, prostate cancer patients underwent preoperative PET/CT imaging with 68Ga-labeled PSMA-914 (n = 10), followed by fluorescence-guided surgery after intraoperative PSMA-914 administration (n = 7, doses ranging from 200 -1500 µg/patient). The optimal dose for effective tumor visualization was retrospectively evaluated, and both preoperative and postoperative imaging results were correlated with histopathological findings. RESULTS: Preoperative PET/CT with [68Ga]Ga-PSMA-914 showed high tracer uptake in primary tumors and metastases, facilitating accurate tumor localization. Intraoperatively, PSMA-914 at doses exceeding 1000 µg/patient provided a clear fluorescence signal, allowing for precise tumor and lymph node delineation. This approach significantly aided surgical resection by providing real-time guidance to differentiate malignant tissue from healthy tissue without altering the standard surgical workflow. Histopathological analysis confirmed the accuracy of [68Ga]Ga-PSMA-914 PET/CT staging. The procedure was well tolerated without adverse effects. CONCLUSION: The dual modality of PSMA-914 has the potential to significantly advance prostate cancer surgery by combining diagnostic imaging and intraoperative guidance. These first results warrant further large-scale clinical trials to validate efficacy and safety across diverse patient populations. The integration of PSMA-914 into clinical protocols promises to benefit prostate cancer surgery by facilitating real-time, high-contrast visualization to aid in complete tumor resection.

Abstract as published, via PubMed.