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Position for site-s...
Position for site-specific attachment of a DOTA chelator to synthetic affibody molecules has a different influence on the targeting properties of 68Ga-Compared to 111in-labeled conjugates
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- Honarvar, Hadis (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Strand, Joanna (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Perols, Anna (författare)
- KTH,Proteinteknologi,Chemical Protein Engineering
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- Orlova, Anna (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap,Plattformen för preklinisk PET
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- Selvaraju, Ram Kumar (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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- Eriksson Karlström, Amelie (författare)
- KTH,Proteinteknologi,Chemical Protein Engineering
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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(creator_code:org_t)
- 2014-12
- 2014
- Engelska.
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Ingår i: Molecular Imaging. - : SAGE Publications. - 1535-3508 .- 1536-0121. ; 13:10
- Relaterad länk:
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https://doi.org/10.2...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Affibody molecules, small (7 kDa) scaffold proteins, are a promising class of probes for radionuclide molecular imaging. Radiolabeling of Affibody molecules with the positron-emitting nuclide 68Ga would permit the use of positron emission tomography (PET), providing better resolution, sensitivity, and quantification accuracy than single-photon emission computed tomography (SPECT). The synthetic anti-HER2 ZHER2:S1 Affibody molecule was conjugated with DOTA at the N-terminus, in the middle of helix 3, or at the Cterminus. The biodistribution of 68Ga-and 111In-labeled Affibody molecules was directly compared in NMRI nu/nu mice bearing SKOV3 xenografts. The position of the chelator strongly influenced the biodistribution of the tracers, and the influence was more pronounced for 68Ga-labeled Affibody molecules than for the 111In-labeled counterparts. The best 68Ga-labeled variant was 68Ga-[DOTA-A1]-ZHER2:S1, which provided a tumor uptake of 13 ± 1 %ID/g and a tumor to blood ratio of 39 ± 12 at 2 hours after injection. 111In-[DOTA-A1]-ZHER2:S1 and 111In-[DOTA-K58]-ZHER2:S1 were equally good at this time point, providing a tumor uptake of 15 to 16 %ID/g and a tumor to blood ratio in the range of 60 to 80. In conclusion, the selection of the best position for a chelator in Affibody molecules can be used for optimization of their imaging properties. This may be important for the development of Affibody-based and other protein-based imaging probes.
Ämnesord
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Biokemikalier (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Biochemicals (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Medicinteknik -- Medicinsk bildbehandling (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Medical Engineering -- Medical Image Processing (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
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