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Improved Radiolytic...
Improved Radiolytic Stability of a 68Ga-labelled Collagelin Analogue for the Imaging of Fibrosis
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- Velikyan, Irina, 1966- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET,PET-Centre, Centre for Medical Imaging, Uppsala University Hospital
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- Rosenström, Ulrika (författare)
- Uppsala universitet,Preparativ läkemedelskemi,Theranostics
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- Rosestedt, Maria (författare)
- Uppsala universitet,Institutionen för läkemedelskemi,Science for Life Laboratory, SciLifeLab
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- Eriksson, Olof (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET
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- Antoni, Gunnar (författare)
- Uppsala universitet,Preparativ läkemedelskemi,Science for Life Laboratory, SciLifeLab,PET-Centre, Centre for Medical Imaging, Uppsala University Hospital
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(creator_code:org_t)
- 2021-09-28
- 2021
- Engelska.
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 14:10
- 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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Abstract
Ämnesord
Stäng
- There is an unmet medical need for non-invasive, sensitive, and quantitative methods for the assessment of fibrosis. Herein, an improved collagelin analogue labelled with gallium-68 for use with positron emission tomography (PET) is presented. A cyclic peptide, c[CPGRVNleHGLHLGDDEGPC], was synthesized by solid-phase peptide synthesis, conjugated to 2-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazonan-1-yl)acetic acid, and labelled with gallium-68. High performance liquid chromatography (HPLC) was used for the quality and stability assessment of the collagelin analogue. Non-specific organ distribution, blood clearance, and excretion rates were investigated in healthy mice and rats using ex vivo organ distribution analysis and dynamic in vivo PET/CT. Mice with carbon tetrachloride (CCl4) induced liver fibrosis were used for the investigation of specific binding via in vitro frozen section autoradiography, ex vivo organ distribution, and in vivo PET/CT. A non-decay corrected radiochemical yield (48 ± 6%) of [68Ga]Ga-NOTA-PEG2-c[CPGRVNleHGLHLGDDEGPC] ([68Ga]Ga-NO2A-[Nle13]-Col) with a radiochemical purity of 98 ± 2% was achieved without radical scavengers. The 68Ga-labelling was regioselective and stable at ambient temperature for at least 3 h. The autoradiography of the cryosections of fibrotic mouse liver tissue demonstrated a distinct heterogeneous radioactivity uptake that correlated with the fibrosis scores estimated after Sirius Red staining. The blood clearance and tissue washout from the [68Ga]Ga-NO2A-[Nle13]-Col was fast in both normal and diseased mice. Dosimetry investigation in rats indicated the possibility for 4–5 PET/CT examinations per year. Radiolytic stability of the collagelin analogue was achieved by the substitution of methionine with norleucine amino acid residue without a deterioration of its binding capability. [68Ga]Ga-NO2A-[Nle13]-Col demonstrated a safe dosimetry profile suitable for repeated scanning.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Nyckelord
- fibrosis
- radiochemistry
- collagen
- collagelin
- positron emission tomography
- gallium-68
- molecular imaging
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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