IMPORTANCE Amyloid-β (Aβ), tau, and cerebral small vessel disease (CSVD), which occasionally coexist, are the most common causes of cognitive impairments in older people. However, whether tau is observed in patients with subcortical vascular cognitive impairment (SVCI), as well as its associations with Aβ and CSVD, are not yet established. More importantly, the role of tau underlying cognitive impairments in SVCI is unknown. OBJECTIVE To investigate the extent and the role of tau in patients with SVCI using 18 F-AV1451, which is a new ligand to detect neurofibrillary tangles in vivo.

Vivax malaria reemerged in the Republic of Korea in 1993. Most of the cases occurred among soldiers in the region adjacent to the Demilitarized Zone (DMZ) until 1995. To determine the rate of dispersion of vivax malaria, we evaluated its epidemiologic characteristics. Of 13,903 cases of vivax malaria reported in 2000, 40.1% (5,577) were reported among Republic of Korea military personnel, 26.2% (3,641) among veterans discharged less than two years from the military, and 33.7% (4,685) among civilians. Cases of vivax malaria have rapidly increased annually among counties bordering the DMZ, and have spread to approximately 40 km south of the DMZ. Chemoprophylaxis administered to military personnel may have been responsible for the decreasing number of cases among the Republic of Korea military population. The first mosquito-transmitted cases appeared in early June. Therefore, chemoprophylaxis should be instituted in early April to reduce the number of infected mosquitoes. Extensive intervention is warranted to reduce the spread of vivax malaria in the Republic of Korea.

We developed an 89 Zr-labeled anti-programmed death ligand 1 (anti-PD-L1) immune PET that can monitor chemotherapy-mediated modulation of tumor PD-L1 expression in living subjects. Methods:Anti-PD-L1 underwent sulfohydryl moiety-specific conjugation with maleimide-deferoxamine followed by 89 Zr radiolabeling. CT26 colon cancer cells and PD-L1 overexpressing CT26/PD-L1 cells underwent binding assays, flow cytometry, and Western blotting. In vivo pharmacokinetics, biodistribution, and PET imaging was evaluated in mice. Results: 89 Zr-anti-PD-L1 synthesis was straightforward and efficient. SDS PAGE showed that reduction produced half-antibody fragments, and MALDI-TOF analysis estimated 2.18 conjugations per antibody, indicting specific conjugation at the hinge region disulfide bonds. CT26/PD-L1 cells showed 102.2 ± 6.7-fold greater 89 Zr-anti-PD-L1 binding compared to weak expressing CT26 cells. Excellent target specificity was confirmed by a drastic reduction of binding by excess cold antibody. Intravenous 89 Zr-anti-PD-L1 followed bi-exponential blood clearance. PET/CT image analysis demonstrated decreases in major organ activity over 7 days, whereas high CT26/PD-L1 tumor activity was maintained. Again, this was suppressed by excess cold antibody. Treatment of CT26 cells with gemcitabine for 24 h augmented PD-L1 protein to 592.4 ± 114.2% of controls and increased 89 Zr-anti-PD-L1 binding. This was accompanied by increased AKT activation and reduced PTEN. In CT26 tumor-bearing mice, gemcitabine treatment substantially increased tumor uptake from 1.56 ± 0.48 to 6.24 ± 0.37 %ID/g (tumor/blood ratio: 34.7). Immunoblots revealed significant increases in tumor PD-L1 and activated AKT and a decrease of PTEN. Conclusion: 89 Zr-anti-PD-L1 showed specific targeting with favorable imaging properties. Gemcitabine treatment upregulated cancer cell and tumor PD-L1 expression and increased 89 Zr-anti-PD-L1 uptake. 89 Zr-anti-PD-L1 PET may thus be useful for monitoring chemotherapy-mediated tumor PD-L1 modulation in living subjects.

A delayed scan is more favorable for the detection of hepatic metastases of colorectal cancer, and the TLR on the delayed scan was the most useful parameter.