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

The patient was a 64-year-old, right-handed man. He graduated from a junior high school at 15 years of age, and worked in a supermarket. There were no notable issues in either his medical or family history. At 60 years of age, he exhibited symptoms including the inability to name products and to comprehend in-store announcements. He visited the authors’ hospital for the first time in 2016, as his symptoms gradually interfered with his work. Proper conduct was maintained, and his spontaneous speech was fluent. However, word-finding difficulty was detected. According to the Neuropsychiatric Inventory (NPI), he had mild depression, possibly caused by his inability to understand the meaning of words, but did not exhibit any behavioral disorders or other findings. Neuropsychological assessment revealed mild anomia, disturbance in word comprehension, and spared repetition (Table 1). In the object-naming subtest of the Western Aphasia Battery (WAB), some tasks revealed anomia, which was not improved after the cues of the initial sound of the words. In the vocabulary subtest of the Wechsler Adult Intelligence Scale-III (WAIS-III), he was unable to provide the definitions of low-frequency words. In the Kanji (Japanese morphogram) reading task, surface dyslexia was detected. He was unable to understand the meanings of idioms and proverbs. Because auditory word recognition was preserved in the Standard Language Test of Aphasia (SLTA), semantic aphasia was considered to be mild. In the face-recognition subtests of the Visual Perception Test for Agnosia (VPTA), prosopagnosia was not detected. Additionally, there was no impairment in recognizing the faces of family members or acquaintances in daily life. No abnormalities were detected in the neurological examination. 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 anterior area of the left temporal lobe. The visual assessment of [¹¹C]Pittsburgh Compound-B (PiB) PET scans, based on the Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI) protocol [11], yielded negative results. His apolipoprotein E phenotype was E3/5 or E3/7. He was diagnosed with svPPA based on the diagnostic criteria developed by Gorno-Tempini et al. [1]. His naming impairment and word comprehension deficits were mild. Moreover, he presented no atrophy in the right temporal lobe. Accordingly, this patient was considered to be in an early stage of the disease. [¹⁸F]THK-5351 PET imaging revealed significant [¹⁸F]THK-5351 retention in the bilateral temporal lobes, predominantly on the left side (Fig. 1 and Additional file 1: Figure S1). Structural MRI revealed brain atrophy in the left anterior temporal pole. [^99mTc]ECD SPECT scan also revealed unilateral hypoperfusion in the left anterior temporal pole. For the comparison of different imaging modalities, Z-score maps of [¹⁸F]THK-5351 PET were created by the comparison of individual PET images with the mean and standard deviation of 20 normal controls, using PMOD software (PMOD Technologies, Zürich, Switzerland). Z-score maps of CBF-SPECT and voxel-based morphometry (VBM)-MRI were also created using easy Z-score imaging system (eZIS) software (Fujifilm RI Pharma., Tokyo, Japan) and voxel-based specific regional analysis system for AD (VSRAD) software (Eisai, Tokyo, Japan) [12, 13]. In the right temporal lobe, the Z-score of [¹⁸F]THK-5351 PET (Z = 3.70) was greater than that of CBF-SPECT (Z < 1.0) and VBM-MRI (Z < 1.0).

The patient was a 79-year-old, right-handed man with 16 years of education. There were no notable issues in either his medical or family history. When he was 77 years of age, his wife noticed that he became unable to name objects used in daily life. During the next two years, his language symptoms had gradually worsened, and he visited the authors’ hospital in 2017. Although his spontaneous speech was fluent and proper conduct was maintained, word-finding difficulty was evident, and his episodic memory in daily life was preserved. According to the NPI, there was no behavioral disorder. Neuropsychological assessment revealed mild anomia, disturbance in word comprehension, and spared repetition (Table 1). In the object-naming subtest of the WAB, some tasks revealed anomia, which was not improved after the cues of the initial sound of the words. In the vocabulary subtest of the WAIS-III, he was unable to provide the definitions of low-frequency words. In the Kanji (Japanese morphogram) reading task, surface dyslexia was detected. He was unable to understand the meanings of idioms and proverbs. Because auditory word recognition was preserved in SLTA, semantic aphasia was considered to be mild. In the face-recognition subtests of the VPTA, prosopagnosia was not detected. Additionally, there was no impairment in recognizing the faces of family members and acquaintances in daily life. No abnormalities were detected on the neurological examination. MRI revealed atrophy in the anterior and inferior portions of the left temporal lobe. [^99mTc]ECD SPECT scan revealed hypoperfusion in the left temporal lobe. [¹¹C]PiB-PET scan was considered to be negative according to the J-ADNI protocol [11], although very mild and focal [¹¹C]PiB retention was observed only in the parietal lobe. His apolipoprotein E phenotype was E3/3. He was diagnosed with svPPA based on the diagnostic criteria developed by Gorno-Tempini et al. [1]. He was considered to be in an early stage of svPPA because of his mild anomia and word comprehension disturbance, and no remarkable atrophy in the right temporal lobe. In [¹⁸F]THK-5351 PET scan, [¹⁸F]THK-5351 retention was observed in the bilateral temporal lobes, predominantly in the left side (Fig. 2 and Additional file 1: Figure S1). In an analysis similar to case 1, Z-score in the right temporal pole was greater in [¹⁸F]THK-5351 PET (Z = 1.27) than in CBF-SPECT (Z < 1.0) and VBM-MRI (Z < 1.0).