Immunization of mice with a 14-mer peptide TKDNNLLGRFELSG, termed "TKD," comprising amino acids 450-461 (aa [450][451][452][453][454][455][456][457][458][459][460][461] ) in the C terminus of inducible Hsp70, resulted in the generation of an IgG1 mouse mAb cmHsp70.1. The epitope recognized by cmHsp70.1 mAb, which has been confirmed to be located in the TKD sequence by SPOT analysis, is frequently detectable on the cell surface of human and mouse tumors, but not on isogenic cells and normal tissues, and membrane Hsp70 might thus serve as a tumor-specific target structure. As shown for human tumors, Hsp70 is associated with cholesterol-rich microdomains in the plasma membrane of mouse tumors. Herein, we show that the cmHsp70.1 mAb can selectively induce antibody-dependent cellular cytotoxicity (ADCC) of membrane Hsp70 + mouse tumor cells by unstimulated mouse spleen cells. Tumor killing could be further enhanced by activating the effector cells with TKD and IL-2. Three consecutive injections of the cmHsp70.1 mAb into mice bearing CT26 tumors significantly inhibited tumor growth and enhanced the overall survival. These effects were associated with infiltrations of NK cells, macrophages, and granulocytes. The Hsp70 specificity of the ADCC response was confirmed by preventing the antitumor response in tumor-bearing mice by coinjecting the cognate TKD peptide with the cmHsp70.1 mAb, and by blocking the binding of cmHsp70.1 mAb to CT26 tumor cells using either TKD peptide or the C-terminal substrate-binding domain of Hsp70.immunotherapy | syngeneic tumor model | tumor antibody dependent cellular cytotoxicity | epitope mapping | surface antigen

Purpose To compare PET/MR hypoperfusion and hypometabolism in patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) compared with healthy control (HC) participants. Materials and Methods Maps of cerebral blood flow (CBF; pulsed arterial spin-labeling [ASL] MRI), glucose metabolism (fluorine 18 [F] fluorodeoxyglucose [FDG] PET), and gray matter (GM) volume (structural T1-weighted MRI) were calculated from integrated PET/MR data in 45 patients with AD (mean age, 69 years ± 9 [standard deviation]; age range, 51-89 years), 20 patients with MCI (mean age, 64 years ± 10; age range, 45-82 years), and 11 HC participants (mean age, 65 years ± 8; age range, 54-80 years) between 2011 and 2014. After preprocessing, voxel-wise analyses of variance, volume of interest, and independent component analyses were performed for comparisons of CBF and glucose metabolism. Results Analyses revealed high overlap between components, regional and quantitative hypoperfusion, and hypometabolism in patients with AD compared with HC participants in precuneus, parietal, temporal, and occipital cortex. In patients with MCI compared with HC participants, FDG PET exclusively demonstrated quantitative hypometabolism and a component in the precuneus. Volume-of-interest analysis in global GM in patients with AD compared with HC participants showed lower CBF (42 mL/100 g per minute ± 8 vs 49 mL/100 g per minute ± 7, respectively; P = .035) and lower FDG uptake (0.8 ± 0.1 vs 1 ± 0.1, respectively; P < .001). Conclusion In patients with AD, pulsed ASL MRI revealed regional and quantitative abnormalities and components similar to F-FDG PET with a reduced extent. In patients with MCI,F-FDG PET exclusively demonstrated quantitative hypometabolism and a component in the precuneus, indicating higher sensitivity to detect preclinical AD compared with the currently used pulsed ASL MRI sequence.

The performance of a recently introduced spectral computed tomography system based on a dual‐layer detector has been investigated. A semi‐anthropomorphic abdomen phantom for CT performance evaluation was imaged on the dual‐layer spectral CT at different radiation exposure levels (CTDI vol of 10 mGy, 20 mGy and 30 mGy). The phantom was equipped with specific low‐contrast and tissue‐equivalent inserts including water‐, adipose‐, muscle‐, liver‐, bone‐like materials and a variation in iodine concentrations. Additionally, the phantom size was varied using different extension rings to simulate different patient sizes. Contrast‐to‐noise (CNR) ratio over the range of available virtual mono‐energetic images (VMI) and the quantitative accuracy of VMI Hounsfield Units (HU), effective‐Z maps and iodine concentrations have been evaluated. Central and peripheral locations in the field‐of‐view have been examined. For all evaluated imaging tasks the results are within the calculated theoretical range of the tissue‐equivalent inserts. Especially at low energies, the CNR in VMIs could be boosted by up to 330% with respect to conventional images using iDose/spectral reconstructions at level 0. The mean bias found in effective‐Z maps and iodine concentrations averaged over all exposure levels and phantom sizes was 1.9% (eff. Z) and 3.4% (iodine). Only small variations were observed with increasing phantom size (+3%) while the bias was nearly independent of the exposure level (±0.2%). Therefore, dual‐layer detector based CT offers high quantitative accuracy of spectral images over the complete field‐of‐view without any compromise in radiation dose or diagnostic image quality.