A Novel 68Ga Labeled FAP Ligand PET/CT in Patients With Various Malignant Tumors (68Ga-GPFAPI)

Comparison of 68Ga-GPFAPI-04 and 18F-FDG PET/CT in Patients With Malignant Tumors

The investigators designed and synthesized a novel fibroblast activation protein (FAP) ligand (DOTA-GPFAPI-04) by assembling three functional moieties: a quinoline-based FAP inhibitor for specifically targeting FAP, a FAP substrate Gly-Pro as a linker for increasing the FAP protein interaction, and a 2,2',2",2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) chelator for radiolabeling with different radionuclides.

Molecular docking studies investigated the FAP targeting ability of DOTA-GPFAPI-04. DOTA-GPFAPI-04 was then radiolabeled with 68Ga to give 68Ga-DOTA-GPFAPI-04 for positron emission tomography (PET) imaging. The investigators found that the 68Ga-DOTA-GPFAPI-04 has high stability, targeted specificity, and longer retention time. The tumor-to-muscle (T/M) ratio for 68Ga-DOTA-GPFAPI-04 reached 9.15.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Metastatic Cancer; Malignant Neoplasm; Tumors
• Intervention / Treatment: Diagnostic test: 68Ga-DOTA-GPFAPI-04 PET/CT

Detailed Description

At the beginning of 2022, the National Cancer Center released the latest statistical data showing that the incidence rate of malignant tumors in China reached 293.91/100000, and the mortality rate reached 174.55/100000. Malignant tumors have become an important public health issue affecting the health of Chinese residents, bringing a heavy economic burden to the public health system. Different from the cancer spectrum in developed countries, digestive system tumors with poor prognosis in China, such as lung cancer, liver cancer, stomach cancer, intestinal cancer, and esophageal cancer, are at a high incidence, while those with good prognosis in European and American developed countries are at a high incidence, such as thyroid cancer, breast cancer and prostate cancer; Even the 5-year survival rate of thyroid cancer, breast cancer and prostate cancer with good prognosis still lags behind that of developed countries such as the United States. The main reason is the low number of early cases, low early diagnosis rate, and non-standard clinical diagnosis and treatment of late cases. Therefore, early detection, diagnosis, staging, and intervention have become urgent issues to be addressed.

Malignant tumors often have insidious onset and overlapping symptoms; Most patients are discovered by chance, and when clinical symptoms and signs are more obvious, patients are often in the late clinical stage. Relying solely on serum tumor markers for diagnosis may result in certain false positives and false negatives. Imaging examination is the preferred and non-invasive evaluation method for malignant tumors, with the advantages of being intuitive and simple. Ultrasound imaging has the advantages of being non-invasive, convenient, and highly accurate in the diagnosis of superficial organs such as the thyroid, breast, and liver. However, the doctor's experience greatly influences the detection results, and the repeatability is poor. Its application in staging, efficacy evaluation, and prognosis follow-up is limited. CT and MR scans can provide detailed and accurate anatomical information for identifying the location of the primary lesion, and local and distant metastases, and are crucial for determining the optimal surgical plan and treatment selection. However, the accuracy of anatomical imaging is limited by the size and morphology of the lesion, and small lesions are prone to misdiagnosis. In addition, some malignant tumor lesions have concealment, making them difficult to detect and diagnose.

The emergence of functional imaging devices has made real-time fusion of anatomical structures and functional/metabolic/biochemical images possible. Positron emission computed tomography/X-ray computed tomography (PET/CT) uses specific molecular probes to target tumor visualization. It can provide detailed information on the biochemical changes of tumor tissue at the cellular and molecular levels, with better sensitivity and specificity than traditional imaging methods, achieving the goal of accurate diagnosis. 18F-FDG is currently the most widely used positron imaging agent in clinical practice, with good sensitivity and specificity for lung cancer. 18F-FDG is not a tumor-specific imaging agent and is susceptible to interference from patient eating and blood glucose levels; Before the examination, the patient needs to have an empty stomach for at least 6 hours, and the blood sugar level needs to be lower than 11.0mmol/L, which is difficult for some diabetes patients to tolerate. The physiological uptake of brain, myocardium, intestinal mucosa, infected tissue, or inflammatory cells can lead to high uptake of 18F-FDG, resulting in a significant increase in false positive rates; In addition, some tumors, such as well-differentiated hepatocellular carcinoma, renal cell carcinoma, and signet ring cell carcinoma, have a low uptake rate of 18F-FDG and a high false negative rate. Therefore, developing new tumor-targeted molecular probes is very important.

The latest research found that in tumor tissues, especially epithelial tumors, such as ovarian cancer, gastric cancer, lung cancer, and breast cancer, the tumor matrix fibroblast membrane highly expresses fibroblast activation protein (FAP), which is a type II transmembrane serine protease. It is worth noting that the liver, ovaries, pancreas, and stomach hardly exhibit FAP activity under normal conditions, but after carcinogenesis, the expression level of FAP is significantly increased. Therefore, based on the upregulation and selective expression of FAP after normal tissue carcinogenesis, it has been identified as a potential biomarker for tumor-associated fibroblasts. In recent years, foreign scholars have achieved very good results in using positron-labeled FAP inhibitors to target FAP and display tumor stroma. Although the studies were based on small sample data or case reports, they achieved significantly better results than 18F-FDG. Therefore, further multi-case and head-to-head studies with 18F-FDG are necessary for various malignant tumors.

Therefore, this study used an intra-individual control to compare the head-to-head comparison between positron-labeled fibroblast activation protein inhibitors and 18F-FDG PET/CT in detecting primary and metastatic lesions of malignant tumors.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Lei Jiang, M.D.; Phone Number: +86 20 8352 5975; Email: jianglei6814@gdph.org.cn
      • Contact: En-Tao Liu, M.D.; Phone Number: +86 15818806018; Email: liuentao@gdph.org.cn
      • Principal Investigator: Lei Jiang, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with high clinical suspicion of malignant tumors;
2. Those who have undergone endoscopic biopsy or puncture biopsy indicating malignant tumors but have not undergone surgery or chemotherapy;
3. Previous history of malignant tumor surgery, suspected of recurrence or distant metastasis;
4. There is a willingness for puncture biopsy or surgery, and there are no contraindications for puncture biopsy or surgery, and there are no contraindications for anesthesia;
5. Sign an informed consent form and undergo a nuclear medicine examination, without any contraindications, with the ability and willingness to participate in the follow-up plan.

Exclusion Criteria:

1. Those who cannot tolerate puncture biopsy or surgical contraindications;
2. Those who have undergone radiotherapy and chemotherapy in the past 3 months;
3. Individuals who are allergic to multiple drugs or foods;
4. Those who refuse nuclear medicine examinations;
5. Those who do not agree to sign an informed consent form and are unable or willing to follow up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 68Ga-DOTA-GPFAPI-04 PET/CT; Imaging was performed 60 minutes after injection of 5mci 68Ga-DOTA-GPFAPI-04 tracer	Diagnostic test: 68Ga-DOTA-GPFAPI-04 PET/CT; The same group of patients underwent 68Ga-DOTA-GPFAPI-04 PET/CT and FDG PET/CT examinations respectively; Other Names: FDG PET/CT examinations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SUVmax (Standardized Uptake Value max)	Manual delineation of the area of interest to measure the maximum standard uptake values of the primary lesion and each metastatic lesion	Within 24 hours after the patient's PET/CT scan is completed

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor-to-background ratios	Manually delineate the area of interest to measure the maximum standard uptake value (SUVmax) of the primary lesion and each metastatic lesion, as well as the average standard uptake value (SUVmean) in the liver and ascending aorta. Using the SUVmax/SUVmean ratio	Within 24 hours after the patient's PET/CT scan is completed

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital
• Collaborators: Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Publications and helpful links

General Publications

• Pang Y, Zhao L, Fang J, Chen J, Meng L, Sun L, Wu H, Guo Z, Lin Q, Chen H. Development of FAPI Tetramers to Improve Tumor Uptake and Efficacy of FAPI Radioligand Therapy. J Nucl Med. 2023 Sep;64(9):1449-1455. doi: 10.2967/jnumed.123.265599. Epub 2023 Jun 15.
• Zhao L, Niu B, Fang J, Pang Y, Li S, Xie C, Sun L, Zhang X, Guo Z, Lin Q, Chen H. Synthesis, Preclinical Evaluation, and a Pilot Clinical PET Imaging Study of 68Ga-Labeled FAPI Dimer. J Nucl Med. 2022 Jun;63(6):862-868. doi: 10.2967/jnumed.121.263016. Epub 2021 Sep 23.
• Lai C, Cao R, Li R, He C, Wang X, Shi H, Qu C, Qian K, Song S, Chen WH, Cheng Z. Fibroblast Activation Protein Targeting Probe with Gly-Pro Sequence for PET of Glioblastoma. Mol Pharm. 2023 Aug 7;20(8):4120-4128. doi: 10.1021/acs.molpharmaceut.3c00248. Epub 2023 Jul 24.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2024
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 15, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 2, 2024

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: PET/CT; PET/MRI; Fibroblast Activation Protein Targeting Probe
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 68Ga-DOTA-GPFAPI-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Case Record Form and Electronic Collection and Management System
• IPD Sharing Time Frame: Within 2 years after the completion of the study
• IPD Sharing Access Criteria: Case Record Form and Electronic Collection and Management System
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No