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Selection of the op...
Selection of the optimal macrocyclic chelators for labeling with 111In and 68Ga improves contrast of HER2 imaging using engineered scaffold protein ADAPT6
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- von Witting, Emma (author)
- KTH Royal Inst Technol, Dept Prot Sci, SE-10691 Stockholm, Sweden
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- Garousi, Javad (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Lindbo, Sarah (author)
- KTH Royal Inst Technol, Dept Prot Sci, SE-10691 Stockholm, Sweden
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- Vorobyeva, Anzhelika (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Altai, Mohamed (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Oroujeni, Maryam, PhD, 1982- (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Mitran, Bogdan (author)
- Uppsala universitet,Theranostics
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- Orlova, Anna, 1960- (author)
- Uppsala universitet,Theranostics
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- Hober, Sophia (author)
- KTH Royal Inst Technol, Dept Prot Sci, SE-10691 Stockholm, Sweden
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English.
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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 140, s. 109-120
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Abstract
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- Radionuclide molecular imaging is a promising tool that becomes increasingly important as targeted cancer therapies are developed. To ensure an effective treatment, a molecular stratification of the cancer is a necessity. To accomplish this, visualization of cancer associated molecular abnormalities in vivo by molecular imaging is the method of choice. ADAPTs, a novel type of small protein scaffold, have been utilized to select and develop high affinity binders to different proteinaceous targets. One of these binders, ADAPT6 selectively interacts with human epidermal growth factor 2 (HER2) with low nanomolar affinity and can therefore be used for its in vivo visualization. Molecular design and optimization of labeled anti-HER2 ADAPT has been explored in several earlier studies, showing that small changes in the scaffold affect the biodistribution of the domain. In this study, we evaluate how the biodistribution properties of ADAPT6 is affected by the commonly used maleimido derivatives of the macrocyclic chelators NOTA, NODAGA, DOTA and DOTAGA with the aim to select the best variants for SPECT and PET imaging. The different conjugates were labeled with 111In for SPECT and 68Ga for PET. The acquired data show that the combination of a radionuclide and a chelator for its conjugation has a strong influence on the uptake of ADAPT6 in normal tissues and thereby gives a significant variation in tumor-toorgan ratios. Hence, it was concluded that the best variant for SPECT imaging is 111In-(HE)3DANS-ADAPT6-GSSC-DOTA while the best variant for PET imaging is 68Ga-(HE)3DANS-ADAPT6-GSSC-NODAGA.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (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)
Keyword
- ADAPT
- HER2
- Radionuclide imaging
- Indium-111
- Gallium-68
- DOTA
- NOTA
- NODAGA
- DOTAGA
Publication and Content Type
- ref (subject category)
- art (subject category)
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von Witting, Emm ...
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Garousi, Javad
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Lindbo, Sarah
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Vorobyeva, Anzhe ...
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Altai, Mohamed
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Oroujeni, Maryam ...
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Mitran, Bogdan
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Orlova, Anna, 19 ...
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Hober, Sophia
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Tolmachev, Vladi ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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Uppsala University