18F-FSPG PET in Imaging Patients With Liver Cancer Before Undergoing Surgery or Transplant

Phase 1

Recruiting

• Conditions: Metastases to Liver; Adult Hepatocellular Carcinoma; Cholangiocarcinoma; Benign Liver Tumor; Resectable Hepatocellular Carcinoma
• Interventions: Biological: Fluorine F 18 L-glutamate Derivative 18F-FSPG; Procedure: Positron Emission Tomography; Biological: Carbon C 11 Acetate; Other: Laboratory Biomarker Analysis; Biological: Fluorine F 18 2-deoxy-2-(18F)fluoro-D-glucose

• Registration Number: NCT02379377
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This clinical trial studies fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) positron emission tomography (PET) in imaging patients with liver cancer before undergoing surgery or transplant. Diagnostic procedures, such as 18F-FSPG PET, may help find and diagnose liver cancer and find out how far the disease has spread.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the relationship between 18F-FSPG PET/computed tomography (CT), pathology, and cancer metabolism in patients with suspected hepatocellular carcinoma (HCC) scheduled for liver resection surgery and orthotopic liver transplant (OLT).

II. To compare 18F-FSPG PET/CT with standard-of-care (SOC) diagnostic MRI imaging in patients with suspected HCC scheduled for liver resection surgery or OLT.

III. To compare the uptake of 18F-FSPG PET/CT with 11C-acetate PET/CT AND 18F-FDG PET/CT in suspected HCC and background liver in patients scheduled for liver resection surgery or OLT.

IV. To evaluate uptake of 18F-FSPG PET/CT in benign liver lesions compared to background.

V. To evaluate uptake of 18F-FSPG PET/CT in malignant non-HCC liver tumors.

OUTLINE:

Patients undergo 18F-FSPG PET and either carbon-11 (11C)-acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.

Study Timeline

• Study First Submitted: 2015-02-06
• Study First Submitted QC: 2015-02-26
• Study First Posted: 2015-03-04
• Study Start: 2022-02-15
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-18
• Primary Completion: 2025-05-31
• Study Completion: 2025-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

1. Diagnosis of HCC with one or more of the following:

   1. Liver mass with non-rim arterial phase hyperenhancement (APHE) and one of the following: 1) 10-19 mm with ≥2 additional major features according to LI-RADS criteria ("washout", enhancing "capsule", and/or threshold growth), 2) 10-19 mm with "washout" and visibility at antecedent ultrasound (US) but with no "capsule" or threshold growth, 3) 10-19 mm with ≥50% size increase in ≤6 months but with no "washout" or "capsule" or 4) ≥20 mm with ≥1 additional major feature according to LI-RADS criteria ("washout", enhancing "capsule", or threshold growth).
   2. Lesions that meet LI-RADS 4 criteria or
   3. Lesions that meet LI-RADS 5 criteria or
   4. Suggestive imaging findings plus AFP > 200 mg/dL or
   5. Tumor confirmed by arteriography or
   6. Pathologic confirmation of tumor or

2. Diagnosis of a benign abdominal or pelvic tumor with the following characteristics:

   1. Liver mass (≥ 1 cm) that has suggestive imaging findings of a benign liver mass (adenoma, hemangioma, focal nodular hyperplasia).
   2. Prior SOC MRI or CT of the benign lesion within 8 weeks of enrollment or

3. Diagnosis of a malignant non-HCC liver tumor with one or more of the following characteristics:

   1. Liver mass (≥ 1 cm) that is biopsy proven, MRI-confirmed, or CT-confirmed metastatic disease (metastatic colorectal cancer, metastatic pancreatic cancer).
   2. Liver mass (≥ 1 cm) that is a non-HCC primary malignancy (cholangiocarcinoma).
   3. Prior SOC MRI or CT of the malignant non-HCC liver tumor within 8 weeks of enrollment or

4. Diagnosis of oligometastatic solid tumors in the following disease sites: colorectal, sarcoma, lung, head and neck, ovarian, renal, melanoma, pancreatic, prostate, cervix, breast, uterine and cholangiocarcinoma undergoing local consolidative therapy.

   and

5. Each patient must have completed conventional imaging and staging and MRI or CT before initiation of the investigational PET studies.

   and

6. Participants with HCC must be a candidate for liver resection, orthotopic liver transplant (OLT), or Y90 radioembolization.

Exclusion Criteria

1. Participants under the age of 18 will be excluded from this study.
2. Participants who have HCC or cholangiocarcinoma but are not candidates for liver resection surgery or OLT, or Y90 radioembolization.
3. Pregnant and breastfeeding patients. Adequate birth control measures (oral, implanted, or barrier methods) must be used by all female participants of childbearing potential until all research PET scans are completed. Female participants of childbearing potential must have a negative serum or urine pregnancy test within 24 hours of the proposed investigational PET/CT scan(s) prior to injection of the investigational radiopharmaceutical.
4. Participants with poorly controlled diabetes mellitus (fasting blood glucose level > 200 mg/dL).
5. Participants with a known Infiltrative variant of HCC.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Diagnostic (18F-FSPG PET)	Fluorine F 18 L-glutamate Derivative 18F-FSPG	Patients undergo an 18F-FSPG PET scan within 4 weeks of surgery or OLT. Patients may also receive a second 18F-FSPG PET scan following standard-of-care treatment.
Diagnostic (11C-Acetate PET or 18F-FDG PET)	Laboratory Biomarker Analysis	Patients may undergo either carbon-11 (11C)-Acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.
Diagnostic (18F-FSPG PET)	Laboratory Biomarker Analysis	Patients undergo an 18F-FSPG PET scan within 4 weeks of surgery or OLT. Patients may also receive a second 18F-FSPG PET scan following standard-of-care treatment.
Diagnostic (11C-Acetate PET or 18F-FDG PET)	Fluorine F 18 2-deoxy-2-(18F)fluoro-D-glucose	Patients may undergo either carbon-11 (11C)-Acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.
Diagnostic (18F-FSPG PET)	Positron Emission Tomography	Patients undergo an 18F-FSPG PET scan within 4 weeks of surgery or OLT. Patients may also receive a second 18F-FSPG PET scan following standard-of-care treatment.
Diagnostic (11C-Acetate PET or 18F-FDG PET)	Fluorine F 18 L-glutamate Derivative 18F-FSPG	Patients may undergo either carbon-11 (11C)-Acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.
Diagnostic (11C-Acetate PET or 18F-FDG PET)	Carbon C 11 Acetate	Patients may undergo either carbon-11 (11C)-Acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.
Diagnostic (11C-Acetate PET or 18F-FDG PET)	Positron Emission Tomography	Patients may undergo either carbon-11 (11C)-Acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.

Primary Outcome Measures

Name	Time	Method
Immunohistochemistry	After surgery; Through study completion, up to 4 years	Tissue samples will be obtained for patients following liver resection surgery. The expression of immunohistochemical markers (ie. xC- and CD44) will be evaluated in these tumor tissues on an ordinal scale of 0, 1, 2 or 3 and correlated to 18F-FSPG PET imaging data. In addition, markers of inflammation and immune cell recruitment (ie. CD86, CD163, CD3), proliferation (Ki67), and apoptosis (Caspase 3) will also be evaluated and correlated to 18F-FSPG PET imaging data.
18F-FSPG PET standardized uptake value (SUV)	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy	The Standardized Uptake Value (SUV) for 18F-FSPG PET images will be determined in the hepatocellular carcinoma (HCC) tumor lesions, non-HCC liver tumors (benign), and background liver (normal tissue). These metrics include SUVmax, SUVpeak, or SUVmean and are common PET imaging measures.
11C-acetate standardized uptake value (SUV)	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy	The Standardized Uptake Value (SUV) for 11C-acetate PET images will be determined in the tumor lesions and background liver (normal tissue). These metrics include SUVmax, SUVpeak, or SUVmean and are common PET imaging measures.
18F-FDG standardized uptake value (SUV)	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy	The Standardized Uptake Value (SUV) for 18F-FDG PET images will be determined in the hepatocellular carcinoma (HCC) tumor lesions and background liver (normal tissue). These metrics include SUVmax, SUVpeak, or SUVmean and are common PET imaging measures.
Pharmacokinetics of 18F-FSPG, 11C-acetate, and 18F-FDG	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy	The pharmacokinetics of 18F-FSPG, 11C-acetate and 18F-FDG uptake will be determined using compartmental modeling of PET imaging data. Venous samples will be collected over the course of 18F-FSPG, 11C-acetate and 18F-FDG scans to confirm blood pool radioactivity, evaluate metabolism, and to calibrate image-derived input functions. We will also utilize blood samples collected prior to scanning to assay plasma levels of carbon-12 acetate and glucose in each patient to explore normalizing pharmacokinetic parameters across patients.
Sensitivity of 18F-FSPG PET imaging	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy	Sensitivity is defined as the true positive rate. It is defined as true positive/(true positive + false negative). The determination of HCC status will be based on diagnostic pathology.
Specificity of 18F-FSPG PET imaging	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy	Specificity is defined as the true negative rate. It is defined as true negative/(true negative + false positive). The determination of HCC status will be based on diagnostic pathology.
Number of lesions	Within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy	The number of lesions detected by 18F-FSPG PET will be determined and compared to the number of lesions detected by standard-of-care MRI, 11C-acetate PET, or 18F-FDG PET on a per patient basis.
Diagnostic pathology	After surgery; Through study completion, up to 4 years	Tissue samples will be obtained for patients following either liver resection surgery or orthotopic liver transplant. Pathology will be performed on these tumor tissues as the gold-standard assessment to confirm the presence of HCC tumor. Histology will be correlated to PET imaging data.
Tumor grade	After surgery; Through study completion, up to 4 years	Tissue samples will be obtained for patients following either liver resection surgery or orthotopic liver transplant. Tumor grade will be determined from pathology of tissue samples and correlated to PET imaging data for 18F-FSPG, 11C-acetate and 18F-FDG PET. The concordance of 18F-FSPG PET/CT and 11C-acetate PET/CT or 18F-FSPG PET/CT and 18F-FDG PET/CT will be evaluated. This will determine whether 18F-FSPG can be used singularly in place of combined use of 11C-acetate PET/CT (which typically detects low grade HCC) and 18F-FDG PET/CT (which typically detects high grade HCC).

Secondary Outcome Measures

Name	Time	Method
Milan classification	Baseline prior to imaging and surgery	Milan criteria will be applied to standard-of-care (SOC) MRI images. The number and size of lesions will be determined. A patient will be deemed to meet Milan criteria if they exhibit A) A single lesion 2 to 5 cm in diameter or B) Three or fewer tumors, each measuring 1 to 3 cm in diameter, and C) No evidence of extrahepatic involvement or microvascular invasion. The proportion of patients whose Milan classification by novel imaging classification changed following validation by histological confirmation will be determined.
Metabolic profile	After surgery; Through study completion, up to 4 years	HCC tumor and non-cancerous liver tissue samples will be obtained for patients following liver resection surgery. Overall, tumoral tissue, peritumoral tissue and grossly normal surrounding liver will be evaluated. Metabolic profiles will be analyzed by mass spectrometry. The unbiased metabolomic phenome will be determined and correlated to 18F-FSPG PET.

Trial Locations

Locations (1)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States