Translational Development of a Zr-89-Labeled Inhibitor of Prostate-specific Membrane Antigen for PET Imaging in Prostate Cancer
| Autor: | Beate Zimmermanns, Heike Endepols, Melanie Hohberg, Felix Dietlein, Klaus Schomäcker, Bernd Neumaier, Alexander Drzezga, Samir-Ghali Tawadros, Sergio Muñoz Vázquez, Markus Dietlein, Thomas Fischer |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Biochemical recurrence
Male Cancer Research Biodistribution Prostate biopsy PET imaging Biokinetics Gallium Radioisotopes urologic and male genital diseases Prostate cancer Mice Prostate carcinoma In vivo Prostate Cell Line Tumor Positron Emission Tomography Computed Tomography ddc:570 LNCaP medicine Animals Humans Radiology Nuclear Medicine and imaging Tissue Distribution Radioisotopes Cell uptake Radiochemistry medicine.diagnostic_test Chemistry Prostatic Neoplasms Zirconium-89 Prostate-Specific Antigen medicine.disease medicine.anatomical_structure Oncology Affinity Positron-Emission Tomography Cancer cell Cancer research Zirconium Research Article |
| Zdroj: | Molecular imaging & biology 24, 115-125 (2022). doi:10.1007/s11307-021-01632-x Molecular Imaging and Biology |
| DOI: | 10.1007/s11307-021-01632-x |
| Popis: | PurposeWe present here a Zr-89-labeled inhibitor of prostate-specific membrane antigen (PSMA) as a complement to the already established F-18- or Ga-68-ligands.ProceduresThe precursor PSMA-DFO (ABX) was used for Zr-89-labeling. This is not an antibody, but a peptide analogue of the precursor for the production of [177Lu]Lu-PSMA-617. The ligand [89Zr]Zr-PSMA-DFO was compared with [68Ga]Ga-PSMA-11 and [18F]F-JK-PSMA-7in vitroby determination of theKdvalue, cellular uptake, internalization in LNCaP cells, biodistribution studies with LNCaP prostate tumor xenografts in mice, andin vivoby small-animal PET imaging in LNCaP tumor mouse models. A first-in-human PET was performed with [89Zr]Zr-PSMA-DFO on a patient presenting with a biochemical recurrence after brachytherapy and an ambiguous intraprostatic finding with [18F]F-JK-PSMA-7 but histologically benign cells in a prostate biopsy 7 months previously.Results[89Zr]Zr-PSMA-DFO was prepared with a radiochemical purity ≥ 99.9% and a very highin vitrostability for up to 7 days at 37 °C. All radiotracers showed similar specific cellular binding and internalization,in vitroand comparable tumor uptake in biodistribution experiments during the first 5 h. The [89Zr]Zr-PSMA-DFO achieved significantly higher tumor/background ratios in LNCaP tumor xenografts (tumor/blood: 309 ± 89, tumor/muscle: 450 ± 38) after 24 h than [68Ga]Ga-PSMA-11 (tumor/blood: 112 ± 57, tumor/muscle: 58 ± 36) or [18F]F-JK-PSMA-7 (tumor/blood: 175 ± 30, tumor/muscle: 114 ± 14) after 4 h (p in vivothat tumor visualization with [89Zr]Zr-PSMA-DFO is comparable to [68Ga]Ga-PSMA-11 or [18F]F-JK-PSMA-7 at early time points (1 h p.i.) and that PET scans up to 48 h p.i. clearly visualized the tumor at late time points. A late [89Zr]Zr-PSMA-DFO PET scan on a patient with biochemical recurrence (BCR) had demonstrated intensive tracer accumulation in the right (SUVmax13.25, 48 h p.i.) and in the left prostate lobe (SUV max 9.47), a repeat biopsy revealed cancer cells on both sides.Conclusion[89Zr]Zr-PSMA-DFO is a promising PSMA PET tracer for detection of tumor areas with lower PSMA expression and thus warrants further clinical evaluation. |
| Databáze: | OpenAIRE |
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