HAHAHA, HEHEHE, HIHIHI, or HKHKHK: Influence of Position and Composition of Histidine Containing Tags on Biodistribution of [Tc-99m(CO)(3)](+)-Labeled Affibody Molecules

HAHAHA, HEHEHE, HIHIHI, or HKHKHK : Influence of Position and Composition of Histidine Containing Tags on Biodistribution of [Tc-99m(CO)(3)](+)-Labeled Affibody Molecules

Altai, Mohamed (author): Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev

Honarvar, Hadis (author): Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev

Strand, Joanna (author): Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev

Malmberg, Jennie (author): Uppsala universitet,Plattformen för preklinisk PET,Anna Orlova

Hosseinimehr, Seyed Jalal (author): Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Yolmachev

Orlova, Anna (author): Uppsala universitet,Plattformen för preklinisk PET,Anna Orlova

Tolmachev, Vladimir (author): Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev

(creator_code:org_t)

2013-06-14
2013
English.
In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:12, s. 4966-4974

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Abstract Subject headings

Engineered affibody molecules can be used for high contrast in vivo molecular imaging. Extending a recombinantly produced HER2 binding affibody molecule with a hexa-histidine tag allows for convenient purification by immobilized metal-ion affinity chromatography and labeling with [Tc-99m(CO)(3)](+) but increases radioactivity uptake in the liver. To investigate the impact of charge, lipophilicity, and position on biodistribution, 10 variants of a histidine-based tag was attached to a HER2 binding affibody molecule. The biochemical properties and the HER2 binding affinity appeared to be similar for all variants. In vivo, positive charge promoted liver uptake. For N-terminally placed tags, promoted liver uptake and decreased kidney uptake. Kidney uptake was higher for C-terminally placed tags compared to their N-terminal counterparts. The variant with the amino acid composition HEHEHE placed in the N-terminus gave the lowest nonspecific uptake.

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)

By the author/editor: Hofström, Camill ...; Altai, Mohamed; Honarvar, Hadis; Strand, Joanna; Malmberg, Jennie; Hosseinimehr, Se ...; show more...; Orlova, Anna; Gräslund, Torbjö ...; Tolmachev, Vladi ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medicinal Chemis ...

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