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

Terbium radioisotopes (Tb-149, Tb-152, Tb-155, Tb-161) offer a unique class of radionuclides which encompass all four medicinally relevant nuclear decay modalities (alpha, beta(+), gamma, beta(-)/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 [(15)5Tb]Tb3+ and [Tb-161]Tb3+, and to assess the imaging and pharmacokinetic properties of each radiotracer in tumour-bearing mice. [Tb-155]Tb-crown-TATE and [Tb-161]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-155- and Tb-161- labelled crown-TATE in male NRG mice bearing AR42J tumours. The radiotracers, [Tb-155]Tb-crown-TATE and [Tb-161]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-155 and Tb-161.

Automated summary

Terbium radioisotopes (Tb-149, Tb-152, Tb-155, Tb-161) possess all four relevant nuclear decay modalities for theranostic radiopharmaceuticals. This study developed crown-TATE as a peptide-conjugate for radiolabeling with Tb-155 and Tb-161, and evaluated their imaging and pharmacokinetic properties in tumor-bearing mice. The radiotracers showed high tumor targeting and minimal retention in non-target organs, suggesting the potential of crown-TATE for molecular imaging and radionuclide therapy.