Axonal transport and MR imaging: Prospects for contrast agent development

Filler, Aaron G.

doi:10.1002/jmri.1880040308

Cited by 21 publications

(12 citation statements)

References 144 publications

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“…We demonstrate possible axonal transport of SPION-sODN (Fig. 5E), an observation that is consistent with reports using other MR contrast agents (Enochs et al, 1993;Filler, 1994;van Everdingen et al, 1994). In the current study, the uptake and distribution of ODN and iron in regions distant from the site of infusion are similar with lipofectin ( Fig.…”

Section: Discussionsupporting

confidence: 78%

Imaging Cerebral Gene Transcripts in Live Animals

Liu

Kim²,

Ren³

et al. 2007

J. Neurosci.

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To circumvent the limitations of using postmortem brain in molecular assays, we used avidin-biotin binding to couple superparamagnetic iron oxide nanoparticles (SPIONs) (15-20 nm) to phosphorothioate-modified oligodeoxynucleotides (sODNs) with sequence complementary to c-fos and ␤-actin mRNA (SPION-cfos and SPION-␤actin, respectively) (14 -22 nm). The Stern-Volmer constant for the complex of SPION and fluorescein isothiocyanate (FITC)-sODN is 3.1 ϫ 10 6 /M. We studied the feasibility of using the conjugates for in vivo magnetic resonance imaging (

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Section: Discussionsupporting

confidence: 78%

Imaging Cerebral Gene Transcripts in Live Animals

Liu

Kim²,

Ren³

et al. 2007

J. Neurosci.

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“…Structure (2) disappears in the STIR image due to fat suppression. Based on this identification, the median nerve (1/1a) is compared to the non-neural structure (2/2a) and is seen to lose intensity in the four and half hour interval between images ( b ) and ( c ) reflecting transport of the WGA-magnetite contrast agent injected in the forearm flexor muscles [24]. The image conspicuity of this structure was measured by multiplying its volume times the intensity in grayscale and this reveals a decrease of 52% in the 270 minute interval.…”

Section: Resultsmentioning

confidence: 99%

“…The underlying physiological basis of this process and its biochemistry are increasingly well understood [10-19]. However, although axonal transport for drug delivery has been proposed previously [20-24], little or nothing is known about the major features of this biological system from the point of view of approaching it pharmacologically and there has been no agent demonstrated capable of accomplishing a pharmacological effect via this route.…”

Section: Introductionmentioning

confidence: 99%

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

et al. 2010

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BackgroundTargeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior.ResultsWe developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle.ConclusionSpecific targeting of selected subpopulations of CNS neurons for drug delivery by axonal transport holds great promise. The data shown here provide a basic framework for the intraneural pharmacology of this tripartite complex. The pharmacologically efficacious drug delivery demonstrated here verify the fundamental feasibility of using axonal transport for targeted drug delivery.

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“…Contrast agents presently do not offer a reliable alternative for current protocols for direct nerve imaging. Intravenous gadolinium enhances nerves in a variable fashion, differing from site to site along a single nerve whether or not the nerve is affected by pathology [49] and intraneural MR contrast agents (for delivery by axonal transport) remain at an early stage in their development [71]. Two-dimensional gradient-recalled-echo magnetisation transfer sequences were found to be more sensitive than T1-weighted spin echo in demonstrating perineural contrast enhancement in CTS, the latter feature being especially useful in the post-operative patient [72].…”

Section: Future Developments In Nerve Imagingmentioning

confidence: 99%

The role of diagnostic radiology in compressive and entrapment neuropathies

et al. 2002

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Diagnostic imaging is increasingly being utilised to aid the diagnosis of compression and entrapment neuropathies. Cross-sectional imaging, primarily ultrasound and magnetic resonance imaging, can provide exquisite anatomical detail of peripheral nerves and the changes that may occur as a result of compression. Imaging can provide a useful diagnostic aid to clinicians, which may supplement clinical evaluation, and may eventually provide an alternative to other diagnostic techniques such as nerve conduction studies. This article describes the abnormalities that may be demonstrated by current imaging techniques, and critically analyses the impact of imaging in diagnosis of peripheral compressive neuropathy.

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Axonal transport and MR imaging: Prospects for contrast agent development

Cited by 21 publications

References 144 publications

Imaging Cerebral Gene Transcripts in Live Animals

Imaging Cerebral Gene Transcripts in Live Animals

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

The role of diagnostic radiology in compressive and entrapment neuropathies

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