Evaluation of F-18 PSMA-11 PET/CT for Diagnostic Accuracy in Staging Hepatocellular Carcinoma Compared to F-18 FDG and F-18 Choline PET/CT

The primary objective of this study is to determine the **diagnostic accuracy** of F-18 PSMA-11 PET/CT for the (re)staging of **hepatocellular carcinoma** (HCC) compared to F-18 FDG PET/CT and F-18 Choline PET/CT. This is clinically relevant as accurate staging is crucial for the effective management and treatment planning of HCC, potentially impacting patient outcomes and survival rates.

Secondary objectives include:

• Comparing overall survival and progression-free survival between subjects with PSMA-avid disease versus those with FDG-avid and Choline-avid disease.
• Evaluating tumor-to-background ratios for intrahepatic lesions.
• Assessing Standard Uptake Value (SUV) parameters for all lesions.
• Determining the proportion of subjects with metastatic disease detected by PSMA PET/CT, versus those detected by FDG and Choline PET.

The clinical trial focuses on participants diagnosed with **hepatocellular carcinoma**. The sponsor has not provided the total number of participants involved in the study. The study population includes both male and female subjects, aged 18 years and older, encompassing a vulnerable population. Participants were selected based on specific clinical scenarios, such as a new diagnosis of hepatocellular carcinoma confirmed by biopsy or imaging, or a known diagnosis requiring restaging. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include the ability to provide informed consent and having undergone or planning to undergo specific PET/CT scans as part of their diagnostic or staging workup. The trial aims to assess the diagnostic accuracy of F-18 PSMA-11 PET/CT in comparison to other imaging modalities for the staging or restaging of hepatocellular carcinoma.

The clinical trial is designed to evaluate the diagnostic accuracy of **F-18 PSMA-11 PET/CT** for the (re)staging of **hepatocellular carcinoma** (HCC) compared to F-18 FDG PET/CT and F-18 Choline PET/CT. This is a Phase IV, randomized, double-blind, controlled study. The trial is expected to commence recruitment on August 1, 2024, and conclude by August 1, 2029. Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being the per-lesion detection rate of F-18 PSMA-11 PET/CT, assessed 60-90 minutes post-injection.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 years or older), mental and legal capacity to provide informed consent, and specific clinical scenarios related to HCC diagnosis or restaging. Participants must have undergone or be scheduled for F-18 FDG PET/CT and F-18 Choline PET/CT scans within four weeks of the study. Follow-up visits will be conducted to monitor overall survival and progression-free survival, with assessments of tumor-to-background ratio and standard uptake value parameters for intrahepatic HCC lesions. The end-of-study visit will mark the completion of the two-year follow-up period for all patients.

Participant involvement is expected to last for the duration of the study, with conditions for early termination including withdrawal of consent or any adverse events that may compromise participant safety. The trial will utilize **gozetotide alf-18** as the active substance, administered via intravenous injection, with a maximum daily and total dose of 2.2 MBq/kg. The study aims to provide comprehensive data on the efficacy of F-18 PSMA-11 PET/CT in detecting metastatic HCC compared to other imaging modalities, contributing valuable insights into the management of hepatocellular carcinoma.

The clinical trial involves the use of the experimental medication **[18F]PSMA-11**, which is a **solution for injection**. The active substance in this formulation is **gozetotide alf-18**, also known by its synonyms **AL(18F)PSMA-11** and **(AL18F)PSMA-HBED**. This compound is chemically synthesized and is administered via **intravenous injection**. The dosage is calculated based on the participant's body weight, with a maximum daily and total dose of 2.2 megabecquerels per kilogram (MBq/kg). The treatment period is limited to a single day.

In this study, **[18F]PSMA-11** is utilized for its potential diagnostic capabilities in the imaging and staging of **hepatocellular carcinoma** (HCC). The trial aims to assess the diagnostic accuracy of **F-18 PSMA-11 PET/CT** in comparison to other imaging modalities such as **F-18 FDG PET/CT** and **F-18 Choline PET/CT**. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial protocol. Participant compliance with the dosing schedule is monitored to ensure adherence to the study protocol.

The clinical trial aims to assess the efficacy of **F-18 PSMA-11 PET/CT** in the imaging and staging of hepatocellular carcinoma (HCC). The primary endpoint for evaluating efficacy is the per-lesion detection rate of F-18 PSMA-11 PET/CT, measured 60-90 minutes post-injection. Secondary endpoints include Overall Survival (OS) and Progression-Free Survival (PFS), which will be measured among subjects with PSMA-avid, FDG-avid, and Choline-avid HCC lesions after a 2-year follow-up period. Additionally, the Tumor-to-Background Ratio for intrahepatic HCC lesions will be assessed 60-90 minutes post-injection using F-18 PSMA-11 PET/CT. Standard Uptake Value (SUV) parameters will be analyzed for all HCC lesions detected within the same timeframe. The proportion of subjects with metastatic HCC will be compared between those detected by F-18 PSMA-11 PET/CT, F-18 FDG PET, and F-18 Choline PET, also 60-90 minutes post-injection.