Evaluation of 99mTc-EUK-(SO3)CY5-MAS3 for PSMA-Targeted Imaging in Prostate Cancer: A Feasibility Study

The primary objective of this study is to confirm the **lesion-specific uptake** of 99mTc-hPSMA in patients with **prostate cancer** (PCa). This is clinically relevant as it aims to validate the targeted imaging capabilities of 99mTc-hPSMA, potentially enhancing the precision of prostate cancer diagnostics and treatment planning.

Secondary objectives include:

• Evaluating the safety and tolerability of 99mTc-hPSMA in patients with primary PCa.
• Assessing the biodistribution and clearance profile of 99mTc-hPSMA at two different time points post-injection in a subset of patients.
• Determining if 99mTc-hPSMA aids in the intraoperative localization of tumor activity within the prostate during robotic-assisted laparoscopic prostatectomy (RALP) that had been previously detected as positive on PSMA-PET/CT and/or PSMA-SPECT/CT.
• Evaluating if 99mTc-hPSMA can assist in detecting positive surgical margins respective to pathology.
• Registering and comparing radioactive and fluorescent signal intensities in background and tumor tissue.
• Evaluating the concordance between 99mTc-hPSMA-based PSMA-SPECT/CT and areas previously detected as positive on PSMA-PET/CT.
• Assessing if 99mTc-hPSMA aids in the intraoperative localization of PSMA-positive lymph nodes at the time of extended pelvic lymph node dissection (ePLND) compared to preoperative PSMA-PET/CT and PSMA-SPECT/CT.
• Evaluating the sensitivity and specificity of 99mTc-hPSMA in detecting small nodal metastases respective to pathology.
• Monitoring for biochemical recurrence at the first post-operative visit.
• Evaluating the signal-to-background ratio of the fluorescent and radioactive signal both in vivo and ex vivo.
• Assessing the surgeons' dexterity during RALP using a drop-in gamma probe.

The clinical trial involves a study population of **male** participants aged 18 years and older, all of whom have been diagnosed with **prostate cancer**. The trial specifically targets individuals with histopathologically confirmed adenocarcinoma of the prostate. Participants must have undergone a routine PSMA PET/CT within 90 days prior to surgery and exhibit a PSMA avid tumor on the PSMA PET/CT. They should be suitable for RALP +ePLND according to institutional guidelines. The trial does not include a vulnerable population, and only male subjects are involved. The sponsor has not provided information regarding the total number of participants. Participants are required to provide written and signed informed consent to be included in the study. No specific lifestyle considerations such as diet or physical activity are mentioned as part of the trial criteria.

The clinical trial is designed to evaluate the **lesion-specific uptake** of 99mTc-hPSMA in patients with **prostate cancer**. This study is a randomized, double-blind, controlled trial, aiming to confirm the uptake of the tracer in prostate cancer lesions. The trial is expected to commence on August 1, 2025, and conclude by August 1, 2027. Participants will be involved in the study for a duration that includes preoperative and postoperative assessments, with the primary endpoint being the presence of lesion-specific uptake of 99mTc-hPSMA.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histopathological confirmation of adenocarcinoma of the prostate, and recent PSMA PET/CT results. Participants will then undergo the investigational procedure, followed by a series of follow-up visits to monitor tracer distribution and assess adverse events according to CTCv5 for 14 days post-injection. The end-of-study visit will occur approximately 3-6 months postoperatively, where PSA levels will be measured, and the overall outcomes will be evaluated.

Participant involvement is expected to last from the initial screening through the final postoperative visit, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The trial will assess both primary and secondary endpoints, including tracer distribution, intra-operative mapping, and the sensitivity and specificity of surgical margin identification. The study will also evaluate the concordance between preoperative imaging and intraoperative findings, as well as the signal-to-background ratio of the tracer in tissues.

The clinical trial involves the administration of an experimental medication known as **hybrid PSMA**. This investigational product is formulated as a **solution for injection in pre-filled syringe**. The active substance in this formulation is **99MTC-EUK-(SO3)CY5-MAS3**, which is a protein-based compound. The medication is administered via **intravenous administration**. The frequency and specific dosage of administration are not detailed in the provided data. The investigational product is not a pediatric formulation and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The trial's main objective is to confirm the lesion-specific uptake of 99mTc-hPSMA in prostate cancer. Participant compliance monitoring and additional dosing schedules are not specified in the available information. The investigational product is developed by the HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS STICHTING, and it is currently authorized for use in this clinical trial.

Efficacy in this clinical trial will be assessed primarily through the presence of lesion-specific uptake of **99mTc-hPSMA** by prostate cancer (PCa). This primary endpoint will be evaluated to confirm the targeted uptake of the tracer in cancerous lesions. Secondary endpoints will include a comprehensive assessment of tracer distribution at specific time points post-injection, namely at 1 hour and 15 hours, in different patient groups. Additionally, intra-operative mapping of prostatic tumor foci using **99mTc-hPSMA** will be conducted to evaluate the tracer's effectiveness in identifying cancerous tissues during surgery.

Further efficacy assessments will involve the sensitivity and specificity of positive surgical margins identification, as well as the concordance rate between preoperative PSMA-PET/CT and PSMA-SPECT/CT imaging results. The trial will also measure the number and location of lymph nodes identified intra-operatively compared to preoperative imaging findings. The sensitivity and specificity of **99mTc-hPSMA** in detecting nodal metastases will be analyzed against histopathological analysis. Additional parameters include the registration of radioactive and fluorescent signal intensities, the signal-to-background ratio of these signals in both in vivo and ex vivo tissues, and the assessment of surgeons' dexterity during robotic-assisted laparoscopic prostatectomy (RALP) using a drop-in gamma probe.