ImmunoPET for prostate cancer in the PSMA era: do we need other targets?

Filippi, Luca; Evangelista, Laura; Sathekge, Mike; Schillaci, Orazio

doi:10.1007/s40336-022-00520-w

Cited by 3 publications

(2 citation statements)

References 60 publications

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“…Significant progress has been made in PCa biomarker discovery, mainly due to advances in genomic technologies. The development of these assays has opened up new opportunities to improve PCa diagnosis, prognosis, and treatment [4].…”

Section: Introductionmentioning

confidence: 99%

Influence of Molecular Design on the Tumor Targeting and Biodistribution of PSMA-Binding Tracers Labeled with Technetium-99m

Bezverkhniaia,

Kanellopoulos,

Rosenström

et al. 2024

IJMS

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Previously, we designed the EuK-based PSMA ligand BQ0413 with an maE3 chelator for labeling with technetium-99m. It showed efficient tumor targeting, but our preclinical data and preliminary clinical results indicated that the renal excretion levels need to be decreased. We hypothesized that this could be achieved by a decrease in the ligand’s total negative charge, achieved by substituting negatively charged glutamate residues in the chelator with glycine. The purpose of this study was to evaluate the tumor targeting and biodistribution of two new PSMA inhibitors, BQ0411 and BQ0412, compared to BQ0413. Conjugates were radiolabeled with Tc-99m and characterized in vitro, using PC3-pip cells, and in vivo, using NMRI and PC3-pip tumor-bearing mice. [99mTc]Tc-BQ0411 and [99mTc]Tc-BQ0412 demonstrated PSMA-specific binding to PC3-pip cells with picomolar affinity. The biodistribution pattern for the new conjugates was characterized by rapid excretion. The tumor uptake for [99mTc]Tc-BQ0411 was 1.6-fold higher compared to [99mTc]Tc-BQ0412 and [99mTc]Tc-BQ0413. [99mTc]Tc-BQ0413 has demonstrated predominantly renal excretion, while the new conjugates underwent both renal and hepatobiliary excretion. In this study, we have demonstrated that in such small targeting ligands as PSMA-binding EuK-based pseudopeptides, the structural blocks that do not participate in binding could have a crucial role in tumor targeting and biodistribution. The presence of a glycine-based coupling linker in BQ0411 and BQ0413 seems to optimize biodistribution. In conclusion, the substitution of amino acids in the chelating sequence is a promising method to alter the biodistribution of [99mTc]Tc-labeled small-molecule PSMA inhibitors. Further improvement of the biodistribution properties of BQ0413 is needed.

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Section: Introductionmentioning

confidence: 99%

Influence of Molecular Design on the Tumor Targeting and Biodistribution of PSMA-Binding Tracers Labeled with Technetium-99m

Bezverkhniaia,

Kanellopoulos,

Rosenström

et al. 2024

IJMS

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“…A variety of other surface targets are currently under evaluation in prostate cancer, including bombesin [ 13 ], prostate stem cell antigen (PSCA) [ 14 ], CUB-domain-containing protein 1 (CDCP-1), CD46 [ 15 , 16 ], human kallikrein 2 (hK2) [ 17 ], delta-like ligand 3 (DLL3) [ 18 , 19 , 20 ], and TROP-2 [ 21 ]. Nevertheless, due to the major advantages of high tumor and low background expression, and highly optimized targeting ligands, PSMA remains by far the most thoroughly investigated theranostic target in prostate cancer [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

PSMA-Targeted Nanotheranostics for Imaging and Radiotherapy of Prostate Cancer

et al. 2023

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Targeted nanotheranostic systems offer significant benefits due to the integration of diagnostic and therapeutic functionality, promoting personalized medicine. In recent years, prostate-specific membrane antigen (PSMA) has emerged as an ideal theranostic target, fueling multiple new drug approvals and changing the standard of care in prostate cancer (PCa). PSMA-targeted nanosystems such as self-assembled nanoparticles (NPs), liposomal structures, water-soluble polymers, dendrimers, and other macromolecules are under development for PCa theranostics due to their multifunctional sensing and therapeutic capabilities. Herein, we discuss the significance and up-to-date development of “PSMA-targeted nanocarrier systems for radioligand imaging and therapy of PCa”. The review also highlights critical parameters for designing nanostructured radiopharmaceuticals for PCa, including radionuclides and their chelators, PSMA-targeting ligands, and the EPR effect. Finally, prospects and potential for clinical translation is discussed.

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