Early clinical experience with ⁶⁸Ga-Trivehexin PET/CT in parathyroid adenomas: a proof-of- concept imaging study

The success of surgical treatment in Primary Hyperparathyroidism (PHPT) depends on the accurate localization of the parathyroid adenoma. Although cervical ultrasonography (USI) and ⁹⁹ᵐTc- Sestamibi scintigraphy are common methods in this context, their diagnostic performance might be limited in small, ectopically located, or biologically atypical lesions. As a novel PET agent targeting integrin αvβ6 (alpha-v beta-6), ⁶⁸Ga-Trivehexin can image biological processes associated with pathological tissue remodeling. This proof-of-concept study aimed to evaluate the feasibility and potential diagnostic contribution of ⁶⁸Ga-Trivehexin PET/CT in detecting parathyroid adenoma in patients with PHPT.

This single-center, prospective proof-of-concept study included 28 patients who had a biochemical diagnosis of PHPT. All patients underwent neck ultrasound, ⁹⁹ᵐTc-Sestamibi parathyroid scintigraphy, and ⁶⁸Ga-Trivehexin PET/CT imaging. Fine Needle Aspiration Biopsy (FNAB) and Parathyroid Hormone (PTH) washout tests were performed for some patients as clinically necessary. Histopathological findings were used as the reference standard in patients who underwent surgery. The agreement between imaging methods was evaluated with Cohen's Kappa coefficient for exploratory purposes.

A total of 64.2% of the patients were female, and the mean age was 56.1 ± 11.3 years. ⁹⁹ᵐTc- Sestamibi scintigraphy was found to be positive in 60.7% of the patients, while the positivity rate for ⁶⁸Ga-Trivehexin PET/CT was 78.6%. A significant proportion of cases with negative ⁹⁹ᵐTc- Sestamibi scintigraphy showed positive lesions with ⁶⁸Ga-Trivehexin PET/CT. Statistically significant, moderate agreement levels were detected in all patients between ⁹⁹ᵐTc-Sestamibi scintigraphy and ⁶⁸Ga-Trivehexin PET/CT (kappa = 0.430; p = 0.013). A moderate level of agreement was observed between the two methods in patients with histopathologically confirmed parathyroid adenoma (kappa = 0.429; p = 0.070).

The results of this proof-of-concept study imply that ⁶⁸Ga-Trivehexin PET/CT may be a feasible and promising imaging method for localizing parathyroid adenomas in patients with primary hyperparathyroidism. It may offer potential contributions as a complementary diagnostic tool, particularly in selected cases where conventional imaging methods are limited. Further large, multicenter studies are needed to confirm these findings.