Role of FAPI PET/CT in the Management of Colorectal Cancer

Introduction: Colorectal cancer ranks as the second leading cause of cancer-related deaths in the United States. Early detection and accurate staging are important for better patient outcomes. In this educational abstract, we aimed to review the role of FAPI PET/CT in managing colorectal cancer.

Methods: A literature review was conducted using PubMed databases and the Google Scholar search engine on FAPI PET/CT in colorectal cancer (CRC). The search terms were "FAPI PET", " FAPI PET/CT" and "colorectal cancer ". Studies were included if they were primary research articles that focused on FAP imaging in primary or metastatic CRC.

Results: Fibroblast-activating protein (FAP) is an enzyme anchored to cell membranes, found in cancer-associated fibroblasts (CAFs), and is elevated in most tumors, fibrotic tissues, and inflammatory processes. However, its presence is notably lower in normal and healthy tissues. It contributes to tumor progression by aiding invasion and metastasis. CAFs play a crucial role in tumor growth, angiogenesis, and immune suppression within the tumor microenvironment, contributing to poor patient prognosis. FAP is highly expressed in CRC cells and tumor stroma, serves as an early indicator of CRC development, and is seen as a promising therapeutic target for CRC. Targeting FAP in imaging through FAPI tracers demonstrates considerable potential in accurately detecting tumors, presenting advantages over the conventional FDG-PET methods. FAPI exhibited significant uptake and favorable Tumor-to-Background Ratios (TBR) in both primary and metastatic CRC, resulting in alterations in TNM clinical staging. For example, heterogeneity affects FDG PET/CT’s accuracy and has limitations for detecting CRC liver metastases. FAPI PET/CT has the potential to enhance the visualization of CRC liver metastases due to its ability to maintain a high TBR, which is aided by the naturally low background FAPI levels in the liver.

In contrast to FDG, FAPI exhibits the potential to detect even small liver metastases, indicating the presence of FAP-expressing cells in the early stages. Compared to FDG PET/CT, the SUV max of FAPI is higher with higher sensitivity and detection rate for primary and metastases colorectal cancer and recurrence detection. FAPI PET/CT improves the detection of lymph node metastases in CRC by highlighting the abundant stroma in both lymph nodes and corresponding metastases. FAPI PET/CT enhanced the quality of identifying peritoneal metastases due to clearer delineation and more distinct outlining of tumors, along with a higher TBR.

Caution is needed as FAPI positivity can also result from inflammation-induced fibrosis, as seen in Crohn's disease and other inflammatory enteritis such as tuberculosis due to elevated FAP expression in activated fibroblasts. Differentiating between heightened FAPI uptake caused by inflammation or colorectal cancer requires interpreting the imaging results considering clinical symptoms and pertinent medical history.

Conclusions: FAPI PET/CT, a novel imaging technique targeting fibroblast activation protein (FAP), exhibits a notable uptake in tumors while maintaining minimal background noise. This results in a favorable tumor-to-background ratio, enhancing its utility in tumor staging. Colorectal cancer has the biological characteristics of high expression of FAP, which provides the foundation for targeted FAP imaging. The potential applications of FAPI PET/CT scans are from altering initial staging and restaging of colorectal cancer to monitoring recurrences, managing treatments, and ultimately augmenting patient prognosis.

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