[¹⁸F]THK-5351 PET imaging in early-stage semantic variant primary progressive aphasia: a report of two cases and a literature review

Background: Semantic variant primary progressive aphasia (svPPA) is a subtype of primary progressive aphasia characterized by two-way anomia and disturbance in word comprehension, with focal atrophy in the left temporal lobe. [¹⁸F]THK-5351 was originally developed to trace tau protein. However, it has recently been suggested that [¹⁸F]THK-5351 binds to monoamine oxidase B in astrocytes, which reflects gliosis. Herein, the authors present two cases involving patients with early-stage svPPA who underwent [¹⁸F]THK-5351 positron emission tomography (PET) imaging, and examined whether [¹⁸F]THK-5351 PET imaging is more sensitive to neurodegenerative lesions than conventional imaging modalities such as magnetic resonance imaging (MRI) and cerebral blood flow (CBF)-single photon emission computed tomography (SPECT).

Case presentation: Two patients, 64- and 79-year-old men, without notable medical or family history, exhibited disturbances in word comprehension and mild anomia with fluent speech and spared repetition. In both cases, surface dyslexia was observed but prosopagnosia was absent. Although mild depression was detected in 1 of the 2 patients, no behavioral disorders were present in either case. In both cases, MRI revealed atrophy in the anterior and inferior portions of the left temporal lobe. Technetium-99-ethyl cysteinate dimer ([^99mTc]ECD) SPECT revealed hypoperfusion in the left temporal lobe. Alzheimer's disease was ruled out by [¹¹C]Pittsburgh Compound-B (PiB) PET scan. Both patients fulfilled the diagnostic criteria for svPPA. Because of mild language deficits and lack of right temporal atrophy, they were considered to be at an early stage of the disease. In both cases, [¹⁸F]THK-5351 retention was observed in bilateral temporal lobes, predominantly on the left side. Comparison of different imaging modalities suggested that [¹⁸F]THK-5351 was more sensitive in detecting neurodegenerative change in the right temporal lobe than MRI and [^99mTc]ECD SPECT.

Conclusions: [¹⁸F]THK-5351 retention was clearly demonstrated at an early stage of svPPA. Results of the present study suggest that [¹⁸F]THK-5351 PET imaging may facilitate very early diagnosis of the disease.