6.1.1. 99mTc-Pertechnetate Scintigraphy

Scintigraphy of the major salivary glands is a nuclear imaging technique that evaluates salivary gland function by uptake and secretion patterns of the radioactive tracer Technetium-99m pertechnetate ( 99mTc-pertechnetate). 99mTc-pertechnetate is actively taken up by salivary gland epithelial cells, probably by using Na+/I− symporters, and secreted into the ductal lumen along with saliva [87]. The technique was included in previous classification criteria of pSS, in which a positive scintigraphy was defined as delayed uptake, reduced concentration, and/or delayed excretion of the tracer [16]. However, due to the low specificity and the inability to differentiate uptake failure from secretory failure, scintigraphy was omitted from the ACR-EULAR classification criteria [14,88]. Various studies stated that scintigraphic examination should focus on the degree of salivary gland dysfunction in pSS, instead of the differentiation between pSS and non-SS [31,89].

Several studies found a relationship between scintigraphic findings and severity of the disease. Brito-Zéron et al. [90] concluded that severe scintigraphic patterns were a prognostic factor for developing extraglandular manifestations. In a large retrospective study by Ramos-Casals et al. [89], patients presenting with severe involvement of the salivary glands according to the scintigraphic examination not only showed increased risk of developing serious extraglandular manifestations, but also a higher risk of developing lymphoma and a lower survival rate. The latter authors also reported that scintigraphic findings worsened during follow-up in 32% of patients. This subgroup of patients also had higher prevalence of high ANA titers, compared to patients with stabilization or improvement of scintigraphy [89]. Furthermore, scintigraphy was associated with histopathological findings within labial salivary glands of pSS patients, as scintigraphic parameters decreased significantly with higher stages of lymphocytic infiltrates graded by Chisholm and Mason's grading system [91–93].
