⁶⁸Ga-FAPI as a PET Agent for the Differentiation of Benign and Premalignant Intraductal Papillary Mucinous Neoplasms

Take-Away Points

• ■ Major Focus: Using gallium 68 (⁶⁸Ga)–labeled fibroblast activation protein inhibitors (FAPI) with PET/CT imaging to identify intraductal papillary mucinous neoplasms (IPMNs) at high risk for malignant transformation.

• ■ Key Results: ⁶⁸Ga-FAPI exhibited differential static and dynamic standardized uptake values (SUVs) in high-grade and menacing IPMNs (men-IPMNs) compared with low-grade IPMNs.

• ■ Impact: ⁶⁸Ga-FAPI PET may serve as a new method in addition to MRI, CT, and endoscopic US imaging to identify IPMNs with a high risk of malignancy.

Resection of men-IPMNs is a critical goal to prevent malignant transformation into pancreatic ductal adenocarcinoma. Selective resection is ideal to avoid complications of pancreatic surgery in cases of IPMN with low-grade dysplasia. Currently, IPMNs are differentiated with CT, MRI, and endoscopic US. However, differentiation using these modalities is widely debated because of deficiencies in specificity and sensitivity, ultimately leading to only one-third of men-IPMNs being resected in a timely manner.

Lang et al evaluated ⁶⁸Ga-FAPI with PET/CT imaging to selectively visualize IPMNs with high uptake of FAPI, and thus, FAP-positive cancer-associated fibroblasts. Twenty patients with a proven pancreatic cyst confirmed via MRI or CT, leading to a diagnosis of IPMN, were administered ⁶⁸Ga-FAPI prior to three-dimensional PET scans. Results indicated increased mean and maximum SUV (SUV_mean and SUV_max, respectively) in men-IPMNs compared with low-grade IPMNs and other benign lesions. Differences in kinetic uptake behavior were also observed, with men-IPMNs showing a gradual relative uptake for approximately 6 minutes prior to a slow decrease, while low-grade IPMNs exhibited immediate peaks followed by rapid decrease. Area under the receiver operating characteristic curve values for each of the static (SUV_max and SUV_mean) and dynamic (time-to-peak) imaging parameters were at least 80%, indicating their high specificity and sensitivity for differentiating low-grade and men-IPMNs.

Static and dynamic ⁶⁸Ga-FAPI PET/CT shows promising results for the differentiation of IPMNs, which may prove helpful in minimizing unnecessary surgery in patients with low-grade IPMNs. These data represent a strong precursor to subsequent investigations on the clinical evaluation of ⁶⁸Ga-FAPI uptake for the detection of malignancy in the pancreas.

Highlighted Article

• Lang M, Spektor AM, Hielscher T, et al. Static and Dynamic 68Ga-FAPI PET/CT for the Detection of Malignant Transformation of Intraductal Papillary Mucinous Neoplasia of the Pancreas. J Nucl Med 2023;64(2):224-251. doi: https://doi.org/10.2967/jnumed.122.264361