First-in-Patient Study of PSMA-Targeted Fluorescent Tracer for Intraoperative Imaging of PSMA-Positive Prostate Cancer

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In a single-institution Dutch phase IIa feasibility trial reported in The Lancet Oncology, Stibbe et al evaluated the pharmacokinetics and safety of the prostate-specific membrane antigen (PSMA)-targeted fluorescent tracer OTL78 in patients undergoing robot-assisted radical prostatectomy for prostate cancer.

Study Details

The study involved 18 eligible patients enrolled at the Netherlands Cancer Institute between June 2020 and 2021 with PSMA positron-emission tomography–avid disease with an International Society of Urological Pathology grade group of 2 or more. All patients underwent robot-assisted radical prostatectomy using OTL78 with or without extended pelvic lymph node dissection. OTL78 dosing cohorts consisted of a single intravenous infusion of either 0.06 mg/kg 1 to 2 hours before surgery (cohort 1), 0.03 mg/kg 1 to 2 hours before surgery (cohort 2), or 0.03 mg/kg 24 hours before surgery (cohort 3). The primary outcome measures were the safety and pharmacokinetics of OTL78.

Key Findings

In 16 (89%) of the 18 patients, robot-assisted radical prostatectomy was accompanied by extended pelvic lymph node dissection.

The most common adverse events of any grade (all grade 1 or 2) were lymphedema (56%), hematoma (28%), urinary incontinence (28%), hematuria (22%), myalgia (17%), and urinary tract infection (17%). Three grade 3 adverse events (lymphocele, urosepsis, and intraperitoneal hemorrhage) occurred in one patient. No adverse events were considered related to the administration of OTL78 or intraoperative fluorescence imaging. No patients died, required a dose reduction, or required discontinuation due to drug-related toxicity.

For the 0.03 mg/kg vs 0.06 mg/kg dose, dose-normalized maximum serum concentration was 84.1 ng/mL/mg vs 79.6 ng/mL/mg, half-life was 5.1 vs 47 hours, volume of distribution was 22.9 L vs 19.5 L, and clearance was 3.1 L/h vs 3.0 L/h.  

It was found that OTL78 could intraoperatively enhance visualization of primary prostate tumors, surgical margins, residual disease in the resection bed, and nodal metastases.  Sensitivities for prostate cancer detection in dose cohorts 1, 2, and 3 were 23.3%, 33.5%, and 65.3% on gross macroscopy and 43.3%, 71.3%, and 88.6% on microscopic slides, respectively.  

The investigators concluded, “This first-in-patient study showed that OTL78 was well tolerated and had the potential to improve prostate cancer detection. Optimal dosing was 0.03 mg/kg, 24 [hours] preoperatively. PSMA-directed fluorescence imaging allowed real-time identification of visually occult prostate cancer and might help to achieve complete oncological resections.”

Henk G. van der Poel, MD, of the Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by On Target Laboratories. For full disclosures of the study authors, visit

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