Preclinical Evaluation of [ 155/161 Tb]Tb-Crown-TATE-A Novel SPECT Imaging Theranostic Agent Targeting Neuroendocrine Tumours

Terbium radioisotopes ( Tb, Tb, Tb, Tb) offer a unique class of radionuclides which encompass all four medicinally relevant nuclear decay modalities (α, , γ, /e ), and show high potential for the development of element-matched theranostic radiopharmaceuticals. The goal of this study was to design, s...

Full description

Saved in:

Bibliographic Details
Published in:	Molecules (Basel, Switzerland) Switzerland), 2023-04, Vol.28 (7), p.3155
Main Authors:	Wharton, Luke, McNeil, Scott W, Merkens, Helen, Yuan, Zheliang, Van de Voorde, Michiel, Engudar, Gokce, Ingham, Aidan, Koniar, Helena, Rodríguez-Rodríguez, Cristina, Radchenko, Valery, Ooms, Maarten, Kunz, Peter, Bénard, François, Schaffer, Paul, Yang, Hua
Format:	Article
Language:	eng
Subjects:	Animals Computed tomography Evaluation Humans Image acquisition Male Medical imaging Mice NETs Neuroendocrine Tumors Peptides Pharmacokinetics Precision Medicine PRRT Radiation Radiation therapy Radioactive tracers Radioisotopes Radioisotopes - therapeutic use Radiolabelling Radiopharmaceuticals - pharmacokinetics Single photon emission computed tomography SPECT imaging Terbium Terbium-155 Terbium-161 theranostics Tissue Distribution Tomography, Emission-Computed, Single-Photon - methods Tumors
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Terbium radioisotopes ( Tb, Tb, Tb, Tb) offer a unique class of radionuclides which encompass all four medicinally relevant nuclear decay modalities (α, , γ, /e ), 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 [ Tb]Tb and [ Tb]Tb , and to assess the imaging and pharmacokinetic properties of each radiotracer in tumour-bearing mice. [ Tb]Tb-crown-TATE and [ 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 Tb- and Tb- labelled crown-TATE in male NRG mice bearing AR42J tumours. The radiotracers, [ Tb]Tb-crown-TATE and [ 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 Tb and Tb.
ISSN:	1420-3049 1420-3049