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Preclinical Evaluation of [<sup>155/161</sup>Tb]Tb-Crown-TATE—A Novel SPECT Imaging Theranostic Agent Targeting Neuroendocrine Tumours
oleh: Luke Wharton, Scott W. McNeil, Helen Merkens, Zheliang Yuan, Michiel Van de Voorde, Gokce Engudar, Aidan Ingham, Helena Koniar, Cristina Rodríguez-Rodríguez, Valery Radchenko, Maarten Ooms, Peter Kunz, François Bénard, Paul Schaffer, Hua Yang
Format: | Article |
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Diterbitkan: | MDPI AG 2023-04-01 |
Deskripsi
Terbium radioisotopes (<sup>149</sup>Tb, <sup>152</sup>Tb, <sup>155</sup>Tb, <sup>161</sup>Tb) offer a unique class of radionuclides which encompass all four medicinally relevant nuclear decay modalities (α, <i>β</i><sup>+</sup>, γ, <i>β</i><sup>−</sup>/e<sup>−</sup>), and show high potential for the development of element-matched theranostic radiopharmaceuticals. The goal of this study was to design, synthesise, and evaluate the suitability of crown-TATE as a new peptide-conjugate for radiolabelling of [<sup>155</sup>Tb]Tb<sup>3+</sup> and [<sup>161</sup>Tb]Tb<sup>3+</sup>, and to assess the imaging and pharmacokinetic properties of each radiotracer in tumour-bearing mice. [<sup>155</sup>Tb]Tb-crown-TATE and [<sup>161</sup>Tb]Tb-crown-TATE were prepared efficiently under mild conditions, and exhibited excellent stability in human serum (>99.5% RCP over 7 days). Longitudinal SPECT/CT images were acquired for <sup>155</sup>Tb- and <sup>161</sup>Tb- labelled crown-TATE in male NRG mice bearing AR42J tumours. The radiotracers, [<sup>155</sup>Tb]Tb-crown-TATE and [<sup>161</sup>Tb]Tb-crown-TATE, showed high tumour targeting (32.6 and 30.0 %ID/g, respectively) and minimal retention in non-target organs at 2.5 h post-administration. Biodistribution studies confirmed the SPECT/CT results, showing high tumour uptake (38.7 ± 8.0 %ID/g and 38.5 ± 3.5 %ID/g, respectively) and favourable tumour-to-background ratios. Blocking studies further confirmed SSTR2-specific tumour accumulation. Overall, these findings suggest that crown-TATE has great potential for element-matched molecular imaging and radionuclide therapy using <sup>155</sup>Tb and <sup>161</sup>Tb.