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Improved Radiolytic Stability of a 68 Ga-labelled Collagelin Analogue for the Imaging of Fibrosis.
- Source :
- Pharmaceuticals (14248247); Oct2021, Vol. 14 Issue 10, p990-990, 1p
- Publication Year :
- 2021
-
Abstract
- 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 (CCl<subscript>4</subscript>) 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 [<superscript>68</superscript>Ga]Ga-NOTA-PEG<subscript>2</subscript>-c[CPGRVNleHGLHLGDDEGPC] ([<superscript>68</superscript>Ga]Ga-NO2A-[Nle<superscript>13</superscript>]-Col) with a radiochemical purity of 98 ± 2% was achieved without radical scavengers. The <superscript>68</superscript>Ga-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 [<superscript>68</superscript>Ga]Ga-NO2A-[Nle<superscript>13</superscript>]-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. [<superscript>68</superscript>Ga]Ga-NO2A-[Nle<superscript>13</superscript>]-Col demonstrated a safe dosimetry profile suitable for repeated scanning. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14248247
- Volume :
- 14
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Pharmaceuticals (14248247)
- Publication Type :
- Academic Journal
- Accession number :
- 153346876
- Full Text :
- https://doi.org/10.3390/ph14100990