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This study investigated the in vivo properties of two heavy chain antibody fragments (VHH), ni3A and pa2H, to differentially detect vascular or parenchymal amyloid-β deposits characteristic for Alzheimer's disease and cerebral amyloid angiopathy. Blood clearance and biodistribution including brain uptake were assessed by bolus injection of radiolabeled VHH in APP/PS1 mice or wildtype littermates. In addition, in vivo specificity for Ab was examined in more detail with fluorescently labeled VHH by circumventing the blood-brain barrier via direct application or intracarotid co-injection with mannitol. All VHH showed rapid renal clearance (10-20 min). Twenty-four hours post-injection 99mTc-pa2H resulted in a small yet significant higher cerebral uptake in the APP/PS1 animals. No difference in brain uptake were observed for 99mTc-ni3A or DTPA(111In)- pa2H, which lacked additional peptide tags to investigate further clinical applicability. In vivo specificity for Aβ was confirmed for both fluorescently labeled VHH, where pa2H remained readily detectable for 24 hours or more after injection. Furthermore, both VHH showed affinity for parenchymal and vascular deposits, this in contrast to human tissue, where ni3A specifically targeted only vascular Aβ. Despite a brain uptake that is as yet too low for in vivo imaging, this study provides evidence that VHH detect Aβ deposits in vivo, with high selectivity and favorable in vivo characteristics, making them promising tools for further development as diagnostic agents for the distinctive detection of different Ab deposits. [ABSTRACT FROM AUTHOR]

Background and Purpose: Although total cerebral blood flow (tCBF) is known to be related to age, less is known regarding the associations between tCBF and the morphologic changes of the brain accompanying cerebral aging. The purpose of this study was to investigate whether total cerebral blood flow (tCBF) is related to white matter hyperintensity (WMH) volume and/or cerebral atrophy. Furthermore, we investigate whether tCBF should be expressed in mL/min, as was done in all previous MR studies, or in mL/100 mL/min, which yielded good results in precious SPECT, PET and perfusion MRI studies investigating regional cerebral blood flow. Materials and Methods: Patients were included from the nested MRI sub-study of the PROSPER study. Dual fast spin echo and FLAIR images were obtained in all patients. In addition, single slice phase contrast MR angiography was used for flow measurements in the internal carotids and vertebral arteries. tCBF was expressed in both mL/min and mL/100 mL/min. Results: We found a significant correlation between tCBF in mL/min and both age (r =-.124; p = p≤.001) and parenchymal volume (r = 0.430; p≤.001). We found no association between tCBF in mL/min and %-atrophy (r =-.077; p = .103) or total WMH volume (r =-.069; p = .148). When tCBF was expressed in mL/100 mL/min the correlation between tCBF and age was no longer found (r =-.001; p = .985). Multivariate regression analyses corrected for age showed a significant correlation between tCBF in mL/100 mL/min and WMH volume (r =-.106; p = .044). No significant association between tCBF in mL/ 100 mL/min and %-atrophy was found. Conclusion: From this study we conclude that, when evaluating tCBF alterations due to various pathologies, tCBF should in mL/100 mL/min instead of mL/min. Furthermore, changes or differences in WMH volume should be accounted for. [ABSTRACT FROM AUTHOR]