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Molecular Design of...
Molecular Design of HER3-Targeting Affibody Molecules : Influence of Chelator and Presence of HEHEHE-Tag on Biodistribution of 68Ga-Labeled Tracers
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- Dahlsson Leitao, Charles (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden
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- Rinne, Sara S. (författare)
- KTH,Uppsala universitet,Theranostics,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden
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- Mitran, Bogdan (författare)
- Uppsala universitet,Theranostics
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- Vorobyeva, Anzhelika (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Andersson, Ken G. (författare)
- KTH,Proteinvetenskap,Skolan för teknikvetenskap (SCI),KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Ståhl, Stefan (författare)
- KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden
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- Löfblom, John (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden
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- Orlova, Anna, 1960- (författare)
- Uppsala universitet,Theranostics,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2019-03-02
- 2019
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 20:5
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.mdpi.com...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Affibody-based imaging of HER3 is a promising approach for patient stratification. We investigated the influence of a hydrophilic HEHEHE-tag ((HE)3-tag) and two different gallium-68/chelator-complexes on the biodistribution of Z08698 with the aim to improve the tracer for PET imaging. Affibody molecules (HE)3-Z08698-X and Z08698-X (X = NOTA, NODAGA) were produced and labeled with gallium-68. Binding specificity and cellular processing were studied in HER3-expressing human cancer cell lines BxPC-3 and DU145. Biodistribution was studied 3 h p.i. in Balb/c nu/nu mice bearing BxPC-3 xenografts. Mice were imaged 3 h p.i. using microPET/CT. Conjugates were stably labeled with gallium-68 and bound specifically to HER3 in vitro and in vivo. Association to cells was rapid but internalization was slow. Uptake in tissues, including tumors, was lower for (HE)3-Z08698-X than for non-tagged variants. The neutral [68Ga]Ga-NODAGA complex reduced the hepatic uptake of Z08698 compared to positively charged [68Ga]Ga-NOTA-conjugated variants. The influence of the chelator was more pronounced in variants without (HE)3-tag. In conclusion, hydrophilic (HE)3-tag and neutral charge of the [68Ga]Ga-NODAGA complex promoted blood clearance and lowered hepatic uptake of Z08698. [68Ga]Ga-(HE)3-Z08698-NODAGA was considered most promising, providing the lowest blood and hepatic uptake and the best imaging contrast among the tested variants.
Ämnesord
- 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)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- HER3
- affibody
- NOTA
- NODAGA
- molecular imaging
- gallium-68
- PET
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Dahlsson Leitao, ...
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Rinne, Sara S.
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Mitran, Bogdan
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Vorobyeva, Anzhe ...
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Andersson, Ken G ...
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Tolmachev, Vladi ...
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Ståhl, Stefan
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Löfblom, John
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Orlova, Anna, 19 ...
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