Potential Efficacy of 68Ga-Trivehexin PET/CT and Immunohistochemical Validation of αvβ6 Integrin Expression in Patients With Head and Neck Squamous Cell Carcinoma and Pancreatic Ductal Adenocarcinoma

Purpose: alpha v beta 6 integrin is exclusively expressed in epithelial cells and is upregulated in many carcinomas, such as pancreatic ductal adenocarcinomas (PDACs) and head and neck squamous cell carcinomas (H&NSCCs). Trivehexin is a recently synthesized trimerized alpha v beta 6 integrin selective nonapeptide, which can be labeled with a positron emitter like( 68)Ga. This is a pilot study to assess the potential role of Ga-68-Trivehexin PET/CT in patients with H&NSCC and PDAC and their correlation with alpha v beta 6 integrin expression by the tumor tissue on immunohistochemistry (IHC). Patients and Methods: Thirty-two patients with suspected H&NSCC (n = 20) or PDAC (n = 12) underwent whole-body Ga-68-Trivehexin PET/CT and F-18-FDG PET/CT scans on 2 separate days. All 32 patients underwent biopsy from the tumor site for histopathological diagnosis and IHC for alpha v beta 6 integrin expression. The degree of alpha v beta 6 integrin expression on IHC was scored using the immunoreactive score and modified 4-point immunoreactive score classification. Results: The Ga-68-Trivehexin PET images demonstrated increased tracer uptake (mean SUVmax 5.9 +/- 3.3) in the primary and metastatic lesions with good lesion delineation in 8 out of the 9 cases of PDACs. However, FDG PET showed increased tracer uptake in 7 cases (6.2 +/- 2.6). Among various cases of H&NSCC, increased uptakes of Ga-68-Trivehexin (6.6 +/- 4.5) and F-18-FDG (12.7 +/- 6.7) were seen in 17 out of the 18 patients. The 2 cases of inflammatory changes with suspected disease recurrence showed increased tracer uptake in F-18-FDG PET (7.98 +/- 3.1) and no significant uptake in 68Ga-Trivehexin PET (2.2 +/- 0.34). IHC showed higher expression of alpha v beta 6 integrins in lesions with higher uptake of 68Ga-Trivehexin. A higher sensitivity, specificity, and accuracy of Ga-68-Trivehexin PET over 18F-FDG PET was seen for detection of primary and metastatic lesions. Conclusions: Ga-68-Trivehexin is a promising noninvasive molecular imaging agent for tumors expressing alpha v beta 6 integrin, especially in cases where F-18-FDG PET/CT scan may be suboptimal due to its low uptake, or due to its nonspecific uptake around tumor sites.