Table of Contents

• Overview of [99mTc]PSMA I&S Clinical Research
• Trial Design and Methodology
• Patient Population and Eligibility
• Intervention and Administration
• Primary Outcomes and Evaluation
• Surgical Application and Imaging Guidance

Overview of [99mTc]PSMA I&S Clinical Research

Clinical trials investigating [99mTc]PSMA I&S focus on improving surgical outcomes for patients with prostate cancer who require lymph node removal^[1]. The research evaluates whether this radioactive imaging agent can help surgeons better identify cancerous lymph nodes during robot-assisted radical prostatectomy^[1]. The primary objective is to enhance clinicians’ ability to detect lymph node invasion in patients undergoing surgery with extended pelvic lymph node dissection^[1].

The substance [99mTc]PSMA I&S is designed to target prostate-specific membrane antigen (PSMA), a protein commonly found on prostate cancer cells. By using this imaging agent during surgery, doctors aim to locate areas where cancer may have spread to nearby lymph nodes more accurately than with traditional surgical techniques alone^[1].

Trial Design and Methodology

The clinical trial investigating [99mTc]PSMA I&S is classified as a Phase 2 interventional study^[1]. Phase 2 trials are designed to evaluate whether a treatment or diagnostic method works effectively in a larger group of patients while continuing to monitor safety. This particular study has been completed and enrolled 100 patients^[1].

The trial uses a specific methodology involving both [99mTc]PSMA I&S and another imaging agent called [68Ga]PSMA-HBED-CC^[1]. This dual-agent approach allows researchers to compare different imaging techniques and determine which provides the best guidance during surgery. The study specifically focuses on implementing imaging guidance during robotic surgery to improve the detection of lymph node involvement^[1].

Patient Population and Eligibility

The clinical trial enrolled patients with specific characteristics to ensure the research addresses the most relevant population. Eligible participants include patients diagnosed with prostate cancer who are candidates for surgical treatment with robot-assisted radical prostatectomy^[1].

A key eligibility criterion is the presence of a greater than 5% risk of lymph nodal invasion based on preoperative data^[1]. This risk assessment is determined before surgery using various tests and clinical information. Patients meeting this threshold are considered to have a sufficient likelihood of lymph node involvement to benefit from enhanced imaging guidance during their surgical procedure.

The trial specifically targets patients who will undergo lymph node removal as part of their cancer treatment. This population represents individuals with more advanced or aggressive prostate cancer where the disease may have spread beyond the prostate gland itself^[1].

Intervention and Administration

The trial involves the administration of two different radioactive imaging agents. The primary agent being studied is [99mTc]PSMA I&S, which is given intravenously at a dose of 850 megabecquerels (MBq)^[1]. Intravenous administration means the substance is injected directly into a vein, allowing it to circulate throughout the body and accumulate in areas where prostate cancer cells are present.

Additionally, patients receive [68Ga]PSMA-HBED-CC at a dose of 160 MBq, also administered intravenously^[1]. Both substances work by targeting the same protein on prostate cancer cells but use different radioactive markers that can be detected with specialized imaging equipment during surgery.

The timing of administration is carefully coordinated with the surgical procedure to ensure the imaging agents have sufficient time to reach and highlight cancerous tissue while the patient is in the operating room. This allows surgeons to use specialized detection equipment during the operation to identify areas that may contain cancer cells.

Primary Outcomes and Evaluation

The primary outcome measure for the trial is the rate of lymph node invasion observed during final pathology examination after surgery guided by 99mTc-PSMA radioguided surgery^[1]. This means researchers evaluate how many patients actually had cancer in their lymph nodes based on laboratory analysis of the removed tissue.

The pathology evaluation is performed by dedicated high-volume uropathologists, who are specialists with extensive experience in examining prostate and urinary system tissues^[1]. This specialized expertise ensures accurate assessment of whether cancer cells are present in the removed lymph nodes.

Results from the pathological examination are typically available approximately 10 days after surgery^[1]. These findings are then compared to what surgeons identified during the operation using the imaging guidance. This comparison helps determine whether the [99mTc]PSMA I&S imaging agent successfully helped surgeons locate cancerous lymph nodes that might have been missed using traditional surgical techniques.

Surgical Application and Imaging Guidance

The implementation of imaging guidance represents a significant advancement in surgical technique for prostate cancer treatment. During robot-assisted radical prostatectomy, surgeons use robotic instruments controlled from a console to perform precise movements while removing the prostate gland and surrounding lymph nodes^[1].

With the addition of [99mTc]PSMA I&S, surgeons can use specialized detection probes during the operation to identify areas emitting radioactivity, which indicates the presence of prostate cancer cells. This technology allows for more targeted removal of affected lymph nodes and potentially reduces the risk of leaving cancerous tissue behind.

The trial specifically evaluates the role of 99mTc-PSMA-I&S in patients undergoing extended pelvic lymph node dissection (ePLND)^[1]. Extended lymph node dissection involves removing a larger number of lymph nodes from the pelvic area compared to standard procedures. The imaging guidance aims to make this extensive surgery more effective by helping surgeons identify exactly which nodes need to be removed.

By improving the detection of lymph node invasion, this imaging approach may help ensure more complete cancer removal, potentially improving long-term outcomes for patients. The completed trial with 100 participants provides valuable data on whether this technology delivers meaningful benefits in real-world surgical settings^[1].