To analyze voxel-wise correlation between cerebral blood flow (CBF) measured using ASL-MRI and cognition in patients with Alzheimer’s disease (AD). Forty-one patients diagnosed with AD or mild cognitive impairment due to AD were recruited for this study. CBF images were obtained using ASL-MRI (n = 41) with a post-labeling delay (PLD) of 1.5 and 2.5 s (PLD1.5 and PLD2.5, respectively) using a 3 T scanner, in addition to brain perfusion SPECT with N-isopropyl-4-[I-123]iodoamphetamine (n = 28). Voxel-based analyses were performed for ASL-MRI and SPECT using Mini-Mental State Examination (MMSE) scores as covariates. Differences in CBF between PLD1.5 and PLD2.5 were assessed using a paired t-test with SPM12. Significant positive correlations were observed between MMSE scores and CBF at PLD1.5 in the right posterior cingulate cortex (PCC), and both temporo-parietal association cortexes. At PLD2.5, significant positive correlations were determined for MMSE scores and CBF in the superior parietal lobule and the right temporo-parietal association cortex. SPECT showed significant positive correlations in the PCC and both temporo-parietal association cortexes (right-side dominant). PLD1.5 showed significantly higher CBF than PLD2.5 in the proximal areas of vascular territories of the anterior, middle, and posterior cerebral arteries. Significant positive correlations in CBF, measured with both ASL-MRI and SPECT, with cognition were found in the PCC and temporo-parietal association cortexes. PLD1.5 and PLD2.5 showed similar correlations with cognition, although the CBF images had significant differences.

We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab. Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study. All patients underwent FDG-PET/CT at baseline and 1 month as a first response assessment, and contrast-enhanced or non-contrast-enhanced CT scan at 4 month as a second response assessment. Logistic regression analysis was performed to assess the association of potential predictors, including age, gender, baseline diameter, baseline maximum standardized uptake value (SUVmax), lung or not lung metastasis, elevation of SUVmax at 1st assessment, and decrease in diameter at 1st assessment with the response at 2nd assessment (decrease in the diameter ≥ 30% or not). There were 9 patients and 30 lesions. Mean days of first assessment with FDG-PET/CT and second assessment by CT scan from initiation of treatment were 32.3 ± 6.4, 115.5 ± 14.9, respectively. Lesions whose diameter decreased ≥30% at second assessment were defined as responding, and lesions whose diameter did not decrease ≥30% were defined as non-responding. There were 18 responding lesions, and 12 non-responding lesions. We compared change in diameter and SUVmax at first assessment with FDG-PET/CT, respectively. All lesions with decreased diameter and elevated SUVmax at first assessment with FDG-PET/CT showed responding at second assessment by CT scan, while most lesions with increased diameter and declined SUVmax at first assessment showed non-responding at second assessment. The multivariate logistic regression analyses revealed that only the elevation of SUVmax at 1 month was an independent predictor (P = 0.025, OR: 13.087, 95%CI: 1.373–124.716). Our findings suggest that the early assessment using FDG-PET/CT can be effective to predict the response of RCC to nivolumab. However, larger prospective studies are needed to confirm these preliminary results. Registered in University Hospital Medical Information Network in JAPAN [ UMIN0000008141 ], registration date: 11 Jun 2012.

Tyrosine-kinase inhibitor (TKI) targeting angiogenesis improves the prognosis of patients with metastatic renal cell carcinoma (RCC), but its effect is temporary. In order to understand the mechanism by which RCC acquires resistance to TKI, we investigated the change of glucose accumulation in RCC by FDG PET/CT when they demonstrated progression disease (PD) against TKI. We monitored the FDG accumulation in RCC of 38 patients treated with TKI by 162 PET/CT sequentially until they were judged to demonstrate PD. Standardized uptake value (SUV), a simplified index of tissue FDG accumulation rate, was measured, and the sequential changes of max SUVmax (the highest SUV in an individual patient) was analyzed. Additionally, the expression of glucose transporter 1 (GLUT-1) and associated proteins in 786-O cells cultured under hypoxia were analyzed. The 10 patients with RCC which FDG accumulation was accelerated after beginning of TKI treatment demonstrated PD soon. The other 28 patients with RCC which FDG accumulation was suppressed by TKI showed longer progression-free survival (3.6 months vs 6.5 months, P = 0.0026), but this suppression in most cases (96%) was temporary and FDG accumulation was accelerated when tumor demonstrated PD. Interestingly, the FDG accumulation at PD was higher than that before TKI treatment in the half cases. The acceleration of FDG accumulation was suppressed by following treatment by mammalian target of rapamycin (mTOR) inhibitor. Additionally, in vitro assay demonstrated that the expression of GLUT-1 was increased in the RCC cells surviving under hypoxia condition via mTOR pathway. The acceleration of glucose accumulation dependent on mTOR in RCC assessed by FDG PET/CT demonstrated acquisition of resistance to TKI. FDG PET/CT had potential as an assessment method monitoring not only the initial response but also following status of RCC during TKI treatment. UMIN0000008141 , 11 Jun 2012. This trial was retrospectively registered.