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Purpose <p>This study investigates the theranostic potential of a <sup>44/47</sup>Sc-labeled antagonist targeting the gastrin-releasing peptide receptor (GRPR) in prostate and breast tumors.</p> Methods <p>A statine-based GRPR antagonist (AAZTA<sup>5</sup>-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH<sub>2</sub>: LF1) was radiolabeled with scandium-44/47. Detailed in vitro evaluation was carried out in PC3 and T47D cancer cells. In vivo studies, including blood and organ clearance, plasma protein binding, metabolic stability and SPECT/CT imaging, were performed in PC3- and T47D-mice. To assess its therapeutic efficacy, PC3-mice were treated with [<sup>47</sup>Sc]Sc-LF1 either alone or in combination with everolimus.</p> Results <p>[<sup>47</sup>Sc]Sc-LF1 exhibited high binding affinity, low internalization rate (&lt; 10% in PC3 and T47D cells), and favorable pharmacokinetics, including rapid blood clearance and low plasma protein binding. In PC3-mice, it demonstrated high and specific tumor uptake (45.4 ± 3.9 and 4.9 ± 1.6% I.A./g at 4 and 96&#xa0;h p.i., respectively), while lower GRPR density in T47D-mice led to reduced uptake (6.1 ± 3.9 and 0.7 ± 0.1% I.A./g at 4 and 72&#xa0;h p.i.). Its pharmacokinetics enabled high-contrast SPECT/CT imaging in both models. Combined treatment with everolimus and [<sup>47</sup>Sc]Sc-LF1 in PC3-mice, significantly inhibited tumor growth compared to monotherapies.</p> Conclusion <p>The high tumor uptake in two cancer entities with elevated expression of GRPR and the tumor response (tumor size and survival rate) highlight the significant theranostic potential of [<sup>44</sup>Sc]Sc/[<sup>47</sup>Sc]Sc-LF1 for PET (scandium-44) and SPECT (scandium-47) imaging and radionuclide targeted therapy.</p>

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A true theranostic pair – 44/47Sc-labeled GRPR antagonist shows great promise for managing prostate and breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月11日

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  • Naveen Kumar,
  • Adrianna Bilinska,
  • Elena Menéndez,
  • Tilman Läppchen,
  • Euy Sung Moon,
  • Malgorzata Zoltowska,
  • Dariusz Pawlak,
  • Izabela Cieszykowska,
  • Renata Mikolajczak,
  • Frank Rösch,
  • Axel Rominger,
  • Eleni Gourni

摘要

Purpose

This study investigates the theranostic potential of a 44/47Sc-labeled antagonist targeting the gastrin-releasing peptide receptor (GRPR) in prostate and breast tumors.

Methods

A statine-based GRPR antagonist (AAZTA5-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2: LF1) was radiolabeled with scandium-44/47. Detailed in vitro evaluation was carried out in PC3 and T47D cancer cells. In vivo studies, including blood and organ clearance, plasma protein binding, metabolic stability and SPECT/CT imaging, were performed in PC3- and T47D-mice. To assess its therapeutic efficacy, PC3-mice were treated with [47Sc]Sc-LF1 either alone or in combination with everolimus.

Results

[47Sc]Sc-LF1 exhibited high binding affinity, low internalization rate (< 10% in PC3 and T47D cells), and favorable pharmacokinetics, including rapid blood clearance and low plasma protein binding. In PC3-mice, it demonstrated high and specific tumor uptake (45.4 ± 3.9 and 4.9 ± 1.6% I.A./g at 4 and 96 h p.i., respectively), while lower GRPR density in T47D-mice led to reduced uptake (6.1 ± 3.9 and 0.7 ± 0.1% I.A./g at 4 and 72 h p.i.). Its pharmacokinetics enabled high-contrast SPECT/CT imaging in both models. Combined treatment with everolimus and [47Sc]Sc-LF1 in PC3-mice, significantly inhibited tumor growth compared to monotherapies.

Conclusion

The high tumor uptake in two cancer entities with elevated expression of GRPR and the tumor response (tumor size and survival rate) highlight the significant theranostic potential of [44Sc]Sc/[47Sc]Sc-LF1 for PET (scandium-44) and SPECT (scandium-47) imaging and radionuclide targeted therapy.