European journal of nuclear medicine and molecular imaging · 2025
A true theranostic pair - 44/47Sc-labeled GRPR antagonist shows great promise for managing prostate and breast cancer.
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Kumar Naveen, Bilinska Adrianna, Menéndez Elena, Läppchen Tilman, Moon Euy Sung, Zoltowska Malgorzata, Pawlak Dariusz, Cieszykowska Izabela, Mikolajczak Renata, Rösch Frank, Rominger Axel, Gourni Eleni
Аннотация
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.
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.