FAPI-PET Surpasses FDG-PET in Detecting Gastrointestinal Cancers: A Paradigm Shift in Oncologic Imaging

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FAPI-PET Surpasses FDG-PET in Detecting Gastrointestinal Cancers: A Paradigm Shift in Oncologic Imaging

Abstract

Recent advances in positron emission tomography (PET) imaging have led to the development of Fibroblast Activation Protein Inhibitor (FAPI)-PET as a revolutionary tool for detecting gastrointestinal (GI) cancers. This article discusses the superior diagnostic performance of FAPI-PET/CT compared to the conventional fluorodeoxyglucose (FDG)-PET/CT. A multicenter study from Xiamen, China, provides compelling clinical evidence highlighting the enhanced sensitivity and imaging efficacy of F-18-labeled FAPI tracers. This column reviews the background, pathophysiology, imaging characteristics, comparative effectiveness, and potential clinical impact of FAPI-PET/CT in GI oncology, especially gastric, liver, and pancreatic cancers.

Introduction

Gastrointestinal malignancies remain a global health burden with high incidence and mortality rates. Accurate staging, restaging, and monitoring of recurrence are vital for effective treatment planning and prognostication. FDG-PET/CT has long been a cornerstone of oncologic imaging, but its limitations in certain cancer types, particularly gastric cancer, have driven the exploration of novel radiotracers. Among these, FAPI-PET/CT has emerged as a promising alternative, targeting the fibroblast activation protein (FAP), which is highly overexpressed in tumor-associated fibroblasts of epithelial cancers.

Background and Scientific Rationale

What is FAP and Why Target It?

Fibroblast Activation Protein (FAP) is a serine protease selectively expressed on cancer-associated fibroblasts (CAFs) in more than 90% of epithelial tumors, but not in normal adult tissues. This tumor microenvironment component plays a critical role in extracellular matrix remodeling, immunosuppression, and tumor progression.

FAPI Radiotracers

FAP-targeted inhibitors (FAPIs), when labeled with radiotracers such as Gallium-68 or Fluorine-18, allow non-invasive visualization of FAP-expressing tissues. F-18 FAPI-74, in particular, offers a longer half-life (110 minutes) and improved logistics for centralized production and imaging workflows compared to Ga-68-labeled agents.

Clinical Evidence: Multicenter Comparative Study

Representative of nine patients who underwent F-18 FDG and F-18 FAPI-74 PET imaging.

In a pivotal prospective study published in the Journal of Nuclear Medicine (October 26), researchers from Xiamen enrolled 112 patients diagnosed with gastric, hepatic, or pancreatic malignancies. Each patient underwent both F-18 FDG-PET/CT and F-18 FAPI-74 PET/CT imaging. Key highlights include:

·         Patient Demographics:

o    Gastric cancer: 49 patients

o    Liver cancer: 39 patients

o    Pancreatic cancer: 24 patients

·         Clinical Purpose:

o    69 patients for initial staging

o    43 patients for recurrence detection

·         Diagnostic Accuracy:

o    FAPI-74 PET/CT showed higher lesion detectability across all categories, including primary tumors, local recurrence, peritoneal, liver, and bone metastases.

Comparative Sensitivity of FAPI vs. FDG PET/CT

Cancer Type

FDG-PET/CT Sensitivity

FAPI-74 PET/CT Sensitivity

Gastric cancer

60%

88%

Liver cancer

82%

100%

Pancreatic cancer

86%

100%

Moreover, FAPI-PET resulted in upstaging in 17 patients and directly influenced clinical decision-making in 4 cases, highlighting its transformative potential.

Case Highlight (Selected Examples)

Representative images from nine patients showed that FAPI-PET outperformed FDG-PET in:

·         Primary tumor detection (Patients 11, 39, 50, etc.)

·         Local recurrence (Patient 4)

·         Lymph node and peritoneal metastases (Patients 4, 85, etc.)

·         Bone metastases (Patient 85)

·         Liver metastases (Patient 50)

These findings underscore the broader lesion contrast, superior tumor-to-background ratio, and increased sensitivity of FAPI tracers.

Discussion

Cause and Etiology

Gastrointestinal cancers, such as gastric, hepatic, and pancreatic cancers, are primarily driven by genetic mutations (e.g., TP53, KRAS), chronic inflammation (H. pylori, hepatitis viruses), dietary factors, and environmental carcinogens. The tumor microenvironment, notably cancer-associated fibroblasts (CAFs), facilitates tumor growth and metastasis via immunosuppression, extracellular matrix deposition, and angiogenesis.

Pathophysiology

The overexpression of FAP in CAFs is a pathophysiological hallmark of many solid tumors. FAP contributes to cancer cell invasion and metastasis by breaking down the extracellular matrix and promoting epithelial-mesenchymal transition (EMT). Unlike FDG, which targets tumor glycolysis, FAPI-PET exploits the tumor stroma, thus offering complementary and often superior imaging insight.

Epidemiology

Gastric cancer is the fifth most common malignancy globally and the third leading cause of cancer-related deaths. Liver cancer ranks as the sixth most common, while pancreatic cancer, though less frequent, has the highest mortality-to-incidence ratio due to late detection.

Clinical Presentation

Symptoms vary by tumor type and stage:

·         Gastric cancer: early satiety, weight loss, epigastric pain

·         Liver cancer: jaundice, right upper quadrant pain

·         Pancreatic cancer: painless jaundice, back pain, weight loss

Imaging Features

·         FDG-PET/CT: Effective in many cancers but limited in mucinous or diffuse-type tumors due to low glucose metabolism.

·         FAPI-PET/CT: Superior contrast in stromal-rich tumors; not influenced by blood glucose levels or dietary state.

Treatment Implications

The improved diagnostic confidence of FAPI-PET supports:

·         Better staging and restaging

·         Tailored surgical planning

·         Monitoring treatment response

·         Potential theranostic applications using FAPI ligands labeled with therapeutic isotopes

Prognosis

Early and accurate detection is directly associated with improved outcomes. With enhanced lesion detectability, FAPI-PET holds promise for enabling earlier interventions, reducing recurrence, and extending survival.

Advantages of FAPI-PET Over FDG-PET

Feature

FDG-PET/CT

FAPI-PET/CT

Tumor background contrast

Moderate

High

Sensitivity in GI cancers

Limited (esp. gastric)

Superior (esp. peritoneal)

Patient preparation required

Fasting, glucose control

None

Imaging workflow

Time-consuming

Faster, centralized

Detectability in low-FDG tumors

Poor

High

Conclusion

The rise of FAPI-PET represents a seismic shift in the imaging of gastrointestinal cancers. With superior lesion detectability, streamlined logistics, and minimal patient preparation, FAPI-PET is poised to redefine oncologic imaging standards. Ongoing studies and multicenter trials will further elucidate its role in routine clinical practice and precision oncology.

References

[1] H. Chen et al., “Fibroblast Activation Protein–Targeted PET/CT with 18F-Fibroblast Activation Protein Inhibitor-74 for Evaluation of Gastrointestinal Cancer: Comparison with 18F-FDG PET/CT,” J. Nucl. Med.., vol. 64, no. 10, pp. 1530–1537, Oct. 2023.

[2] G. Kratochwil et al., “FAPI PET/CT: tracer uptake in 28 different kinds of cancer,” J. Nucl. Med.., vol. 60, no. 6, pp. 801–805, Jun. 2019.

[3] J. Loktev et al., “A novel FAP-targeted radiotracer for PET imaging: synthesis and preclinical evaluation of FAPI-04,” J. Nucl. Med.., vol. 59, no. 9, pp. 1415–1422, Sept. 2018.

[4] C. Kesch et al., “FAP imaging in prostate cancer: initial experience with FAPI PET,” Eur. J. Nucl. Med.. Mol. Imaging, vol. 47, no. 5, pp. 1395–1406, May 2020.

[5] L. Pang et al., “FAPI PET/CT in colorectal cancer: a comparative study with FDG PET/CT,” Clin. Nucl. Med., vol. 48, no. 1, pp. e45–e52, Jan. 2023.

[6] R. Röhrich et al., “FAPI-PET for non-oncologic imaging: possibilities and pitfalls,” J. Nucl. Med.., vol. 62, no. 4, pp. 513–520, Apr. 2021.

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