Page 101 - New epidemiological and PSMA-expression based paradigms in salivary gland tumors

Distribution of PSMA-ligand in salivary and lacrimal glands on PET/CT
Introduction
Functional imaging of tissues expressing the prostate-specific membrane antigen (PSMA) with radiolabelled ligand Gallium-68 [68Ga]-HBED-CC-Glu-NH-CO- NH-Lys(Ahx) and positron emission tomography combined with computed tomography (PSMA PET/CT), is primarily used for the detection and (re)staging of prostate cancer [1].
However, binding of PSMA-ligands is not limited to prostate cancer cells. Clinical experience with PSMA PET/CT for prostate cancer has revealed consistent and significant uptake in other tissues, most notably the major salivary and lacrimal glands [1]. Because tracer uptake is based on expression of the PSMA epitope in present glandular cells, it can be hypothesized that uptake of PSMA-ligand is associated with gland volume and thus functional capacity of the gland. Two arguments support this hypothesis. First, xerostomia is a well-known side effect of lutetium-177 (177Lu)-PSMA treatment and could be explained by cell loss as a consequence of toxicity. Second, a difference can be noted in 68Ga-PSMA uptake between normal and irradiated submandibular glands, with the latter having decreased glandular function after radiotherapy (Figure 1) [2,3]. Current clinical tomographic imaging modalities such as CT, magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) PET/CT can adequately visualize the parotid and submandibular salivary glands, and clinicians are generally well aware of their normal location and appearance [4].
The sublingual glands are more difficult to detect on CT or FDG PET/CT and they require specific magnetic resonance sequences for good visualization [5]. Imaging of the minor (mucosal) salivary glands with current techniques has been a challenge because until now adequate visualization of these small (1-5mm) glands was impossible. Imaging experts may not even be aware of their existence. In addition, the lack of tools to visualize minor salivary and seromucous glands, and the inability to estimate gland viability limits the options for personalized treatment aiming to preserve the function of these glands, which play a vital role in lubrication of the oral cavity [6,7].
With the introduction of PSMA PET/CT for prostate cancer staging and follow- up, clinicians are confronted with unfamiliar uptake patterns throughout the
6
99