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A survey of research activity on nanoparticles (NPs) based on polymeric devices that could cross the blood-brain barrier (BBB) is given along with the presentation of our own data on the development of NPs of n-butyl-2-cyanoacrylate (BCA) for brain delivery to aid the early diagnosis of Alzeimer's disease (AD), a neurodegenerative disorder of the elderly people, the most prevalent form of dementia. Typical data are presented on in vivo detection of amyloid peptides (Aβ) (amyloid plaques) that are used as targets for developing the biological markers for the diagnosis of AD. In order to develop efficient in vivo probes, polymeric n-butyl-2-cyanoacrylate (PBCA) NPs have been prepared and encapsulated with the radio-labeled amyloid affinity drug I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) to improve the transport to brain and amyloid plaque retention of I-CQ using the NPs of PBCA. The I-CQ discriminately binds to the AD post-mortem brain tissue homogenates versus control. I-CQ-PBCA NPs labeled the Aβ plaques from the AD human post-mortem frontal cortical sections on paraffin-fixed slides. Storage phosphor imaging verified preferential uptake by AD brain sections compared to cortical control sections. The I-CQ-PBCA NPs crossed the BBB in wild type mouse, giving an increased brain uptake measured in terms of % ID/g i.e., injected dose compared to I-CQ. Brain retention of I-CQ-PBCA NPs was significantly increased in the AD transgenic mice (APP/PS1) and in mice injected with aggregated Aβ42 peptide versus age-matched wild type controls. The results of this study are verified by in vivo storage phosphor imaging and validated by histopathological staining of plaques and select metal ions, viz. Fe and Cu. The I-CQ-PBCA NPs had more efficient brain entry and rapid clearance in normal mice and enhanced the retention in AD mouse brain demonstrating the ideal in vivo imaging characteristics. The I-CQ-PBCA NPs exhibited specificity for Aβ plaques both in vitro and in vivo. This combination offered radio-iodinated CQ-PBCA NPs as the promising delivery vehicle for in vivo single photon emission tomography (SPECT) (I) or PET (I) amyloid imaging agent. The importance of the topic in relation to brain delivery and other similar type of work published in this area are covered to highlight the importance of this research to medical disciplines. WIREs Nanomed Nanobiotechnol 2010 2 35-47 For further resources related to this article, please visit the . [ABSTRACT FROM AUTHOR]

Detecting aggregated amyloid peptides (Aβ plaques) presents targets for developing biomarkers of Alzheimer's disease (AD). Polymeric n-butyl-2-cyanoacrylate (PBCA) nanoparticles (NPs) were encapsulated with radiolabelled amyloid affinity 125I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) as in vivo probes. 125I-CQ-PBCA NPs crossed the BBB (2.3±0.9 ID/g) (P < .05) in theWTmouse (N = 210), compared to 125I-CQ (1.0±0.4 ID/g). 125I-CQ-PBCA NP brain uptake increased in AD transgenic mice (APP/PS1) versusWT (N = 38; 2.54×105±5.31×104 DLU/mm2; versus 1.98×105±2.22×104 DLU/mm2) and in APP/PS1/Tau. Brain increases were in mice intracranially injected with aggregated Aβ42 peptide (N = 17; 7.19 × 105 ± 1.25 × 105 DLU/mm2), versusWT (6.07×105 ±7.47×104 DLU/mm2). Storage phosphor imaging and histopathological staining of the plaques, Fe2+ and Cu2+, validated results. 125I-CQ-PBCA NPs have specificity for Aβ in vitro and in vivo and are promising as in vivo SPECT (123I), or PET (124I) amyloid imaging agents. [ABSTRACT FROM AUTHOR]

A Small Animal Imager (SAI) for PET has been designed, built, tested in phantoms, and applied to investigations in mice and rats. The device uses principles based on γ-ray induced scintillation in crossed fiber optic detectors connected to Position Sensitive Photomultiplier Tubes (PSPMT). Each detector consists of an epoxied stack of 28 layers of 135 round 1 mm BCF-10 scintillating plastic fibers. The overlap region forms a 13.5 × 13.5 × 2.8 cm³ detector volume. Scintillating light from the fibers is detected by two (X and Y directions) Hamamatsu R-2486 PSPMTs with 16 anode wires in each of two orthogonal directions. A centroid-finding algorithm gives the position of a light cluster on the face (photocathode) of a PSPMT. The accuracy of the reconstruction of an interaction position is essentially independent of light cluster position. This translates to a nearly isotropic photon response for the entire detector. The system has been used to test several 3D image reconstruction algorithms, software modifications, and improvements. The sensitivity (∼12.6 cps/kBq at 9 cm inner diameter) and sub-millimeter spatial resolution (better than 1 mm in phantoms) obtained with an iterative algorithm incorporating system modeling make the SAI a relatively inexpensive high performance animal imager. The SAI is currently being used for imaging experiments in mice and rats. [ABSTRACT FROM AUTHOR]