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  Development of MR guided probes for biotin/avidin based targeting techniques

Dhingra, K., Mishra, A., Engelmann, J., Maier, M., & Logothetis, N. (2009). Development of MR guided probes for biotin/avidin based targeting techniques. Poster presented at 4th Europen Molecular Imaging Meeting (EMIM 2009), Barcelona, Spain.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-14C9-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-14CA-3
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Dhingra, K1, 2, Author              
Mishra, A1, 2, Author              
Engelmann, J2, 3, Author              
Maier, ME, Author
Logothetis, NK1, 2, Author              
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1Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497798              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497794              
3Former Department MRZ, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_2528700              

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 Abstract: introduction: Molecular imaging has an important role in diagnosis and thus the effective treatment of diseases. Several strategies have been developed to specifically target/trace the early biochemical, physiological and anatomical changes under pathological conditions. The development of molecular probes selectively binding the biochemical targets has proved to be a boon in this area. The most common strategy for designing these probes make use of the monoclonal antibody (mab) fragments, high affinity mab, pretargeting strategies etc. The pretargeting techniques using the high affinity of biotin to avidin has proved to be the most efficient technique for selective accumulation of the probes at the target site 1. Methods: The basic skeleton of the molecules is do3a, functionalized and linked to biotin. The linking is done in a way to increase the stability toward cleavage action of the biotinidase. Two complexes, gd-biotin1 and gd-biotin2, have been synthesized and characterized by 1h nMr, 13C nMr, and eSi-MS. The synthesized ligands were finally loaded with gadolinium and the exact concentration of the complexes obtained was determined by bulk magnetic shift method. The relaxivity in the absence and presence of avidin was measured at various magnetic fields (1.5T, 4.7T, 7T, and 9.4T). Shin-3 cells were measured with the complexes (+/- avidin) and relaxation times were estimated in these cells at 3T in order to test if the magnetic properties are maintained in cellular system. results: The in vitro relaxivity measurement of gd-biotin1 and -2 with avidin in buffer demonstrated different longitudinal (r1) and transverse relaxation (r2) behaviour. gd-biotin1 enhanced r2 by ~1000% with the addition of avidin at all four magnetic fields, while r1 showed field dependent response. at 9.4 T 47% decrease, at 7T 31% decrease; at 3T 82% increase and at 1.5 T an increase of 266% was observed. on the otherhand, r1 of gd-biotin2 decreased by ~ 200% at 9.4T and 7T, 40% at 3T and increased by 40% at 1.5T. The r2 however, showed an increase of 240% at 7T. The measurement of r2 at other magnetic field is under progress. labelling of Shin-3 cells with these complexes did not induce similar T1/T2 changes inside the cells. no significant enhancement in r2 was detectable for gd-biotin1 and -2 at 3T while r1 increased by 10-14%. This might be due to the uptake of the complex into the cells by endocytosis. as the agent remains trapped in the vesicles, the contact with water molecules is limited, preventing the relaxivity enhancement as it was observed in buffer. Conclusions: The in vitro relaxivity data shows that the two complexes although only slightly vary in the linker connecting biotin and gd-do3a but shows very different behaviour toward their binding affinity to avidin and thus on the observed relaxivity. amongst the two complexes, gd-biotin1 showed the most promising r2/r1 behaviour in the presence of avidin. at 1.5 T, a marked increase in both r1 and r2 was observed which indicates that the agent could be used as T1 agent as well as T2 agent. The structural design also offers the stability against biotinidase degradation which is important for the in vivo applications. The results obtained with Shin-3 cells indicate that such complexes should only be used for extracellular tagging of cell and internalization should be avoided in order to maintain the strong T2 effects of the probe.

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 Dates: 2009-05
 Publication Status: Published online
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Title: 4th Europen Molecular Imaging Meeting (EMIM 2009)
Place of Event: Barcelona, Spain
Start-/End Date: 2009-05-27 - 2009-05-30

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Title: 4th Europen Molecular Imaging Meeting (EMIM 2009)
Source Genre: Proceedings
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Pages: - Volume / Issue: - Sequence Number: 26 Start / End Page: 186 Identifier: -