Radiolabeled PSMA Inhibitors

Neels, Oliver; Kopka, Klaus; Liolios, Christos; Afshar‐Oromieh, Ali

doi:10.3390/cancers13246255

Cited by 24 publications

(31 citation statements)

References 245 publications

(250 reference statements)

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“…PSMA-targeted PET/ CT has become increasingly important in the management of prostate cancer for initial staging, localization of biochemical This article is part of the Topical Collection on Oncology -Genitourinary recurrence, and screening or monitoring of PSMA-targeted radioligand therapy [5][6][7][8]. In recent years, various PSMA-ligands have been developed, of which 68 Ga-labeled PSMA-11 and 18 F-labeled DCFPyL or PSMA-1007 have become widely used for PET/CT imaging in clinical practice, and 177 Lu-labeled PSMA-617 for radioligand therapy [9,10].…”

Section: Introductionmentioning

confidence: 99%

[89Zr]Zr-PSMA-617 PET/CT in biochemical recurrence of prostate cancer: first clinical experience from a pilot study including biodistribution and dose estimates

Rosar

Schaefer-Schuler

Bartholomä

et al. 2022

Eur J Nucl Med Mol Imaging

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Purpose Prostate-specific membrane antigen (PSMA)-targeted PET/CT has become increasingly important in the management of prostate cancer, especially in localization of biochemical recurrence (BCR). PSMA-targeted PET/CT imaging with long-lived radionuclides as 89Zr (T1/2 = 78.4 h) may improve diagnostics by allowing data acquisition on later time points. In this study, we present our first clinical experience including preliminary biodistribution and dosimetry data of [89Zr]Zr-PSMA-617 PET/CT in patients with BCR of prostate cancer. Methods Seven patients with BCR of prostate cancer who revealed no (n = 4) or undetermined (n = 3) findings on [68Ga]Ga-PSMA-11 PET/CT imaging were referred to [89Zr]Zr-PSMA-617 PET/CT. PET/CT imaging was performed 1 h, 24 h, 48 h, and 72 h post injection (p.i.) of 111 ± 11 MBq [89Zr]Zr-PSMA-617 (mean ± standard deviation). Normal organ distribution and dosimetry were determined. Lesions visually considered as suggestive of prostate cancer were quantitatively analyzed. Results Intense physiological uptake was observed in the salivary and lacrimal glands, liver, spleen, kidneys, intestine and urinary tract. The parotid gland received the highest absorbed dose (0.601 ± 0.185 mGy/MBq), followed by the kidneys (0.517 ± 0.125 mGy/MBq). The estimated overall effective dose for the administration of 111 MBq was 10.1 mSv (0.0913 ± 0.0118 mSv/MBq). In 6 patients, and in particular in 3 of 4 patients with negative [68Ga]Ga-PSMA-11 PET/CT, at least one prostate cancer lesion was detected in [89Zr]Zr-PSMA-617 PET/CT imaging at later time points. The majority of tumor lesions were first visible at 24 h p.i. with continuously increasing tumor-to-background ratio over time. All tumor lesions were detectable at 48 h and 72 h p.i. Conclusion [89Zr]Zr-PSMA-617 PET/CT imaging is a promising new diagnostic tool with acceptable radiation exposure for patients with prostate cancer especially when [68Ga]Ga-PSMA-11 PET/CT imaging fails detecting recurrent disease. The long half-life of 89Zr enables late time point imaging (up to 72 h in our study) with increased tracer uptake in tumor lesions and higher tumor-to-background ratios allowing identification of lesions non-visible on [68Ga]Ga-PSMA-11 PET/CT imaging.

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Section: Introductionmentioning

confidence: 99%

[89Zr]Zr-PSMA-617 PET/CT in biochemical recurrence of prostate cancer: first clinical experience from a pilot study including biodistribution and dose estimates

Rosar

Schaefer-Schuler

Bartholomä

et al. 2022

Eur J Nucl Med Mol Imaging

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“…A growing body of literature reported remarkable results for PSMA-targeted imaging and therapy in prostate cancer [ 8 , 9 , 10 , 11 , 12 ]. To date, most clinical research on PSMA-targeted imaging and therapy focuses on prostate cancer due to the high level of PSMA expression by prostate cancer tumor cells [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Prostate specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II, is a membrane antigen overexpressed in the majority of prostate cancer cells; therefore, PSMA has proven to be a good target for diagnosis and therapy (theranostics) of prostate cancer using a variety of radiolabelled PSMA-targeting radiopharmaceuticals [ 8 , 9 , 10 ]. Undoubtedly, PSMA PET is a hot topic of imaging in the last years.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Accuracy of PET/CT or PET/MRI Using PSMA-Targeting Radiopharmaceuticals in High-Grade Gliomas: A Systematic Review and a Bivariate Meta-Analysis

et al. 2022

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Background: Several studies proposed the use of positron emission tomography (PET) with Prostate Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in brain tumors. Our aim is to calculate the diagnostic accuracy of these methods in high-grade gliomas (HGG) with a bivariate meta-analysis. Methods: A comprehensive literature search of studies on the diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG was performed. Original articles evaluating these imaging methods both in the differential diagnosis between HGG and low-grade gliomas (LGG) and in the assessment of suspicious HGG recurrence were included. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) including 95% confidence intervals (95% CI) were calculated. Statistical heterogeneity was also assessed using the I2 test. Results: The meta-analysis of six selected studies (157 patients) provided the following results about PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in the diagnosis of HGG: sensitivity 98.2% (95% CI: 75.3–99.9%), specificity 91.2% (95% CI: 68.4–98.1%), LR+ 4.5 (95% CI: 2.2–9.3), LR− 0.07 (95% CI: 0.04–0.15), and DOR 70.1 (95% CI: 19.6–250.9). No significant statistical heterogeneity among the included studies was found (I2 = 0%). Conclusions: the quantitative data provided demonstrate the high diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HGG detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in this clinical setting.

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“…Various PSMA ligands have been developed so far as diagnostics or therapeutics for PCa . Among them, [ 68 Ga]Ga-PSMA-11 ( 1 ) (gozetotide), initially developed by our team, has been recently approved by the Food and Drug Administration (1st December 2020) for PET diagnosis of PCa and is considered the most prominent radioligand for PET imaging of PCa, especially for cases showing increased PSA levels post castration.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Tumor Cells and Receptor-Ligand Simulation Models for the Development of PET Imaging Probes Targeting PSMA and GRPR and a Possible Crosstalk between the Two Receptors

et al. 2022

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Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) have both been used in nuclear medicine as targets for molecular imaging and therapy of prostate (PCa) and breast cancer (BCa). Three bioconjugate probes, the PSMA specific: [ 68 Ga]Ga-1, ((HBED-CC)-Ahx-Lys-NH-CO-NH Glu or PSMA-11), the GRPR specific: [ 68 Ga]Ga-2, ((HBED-CC)-4-amino-1-carboxymethyl piperidine-[D-Phe 6 , Sta 13 ]BN(6−14), a bombesin (BN) analogue), and 3 (the BN analogue: 4-amino-1-carboxymethyl piperidine-[(R)-Phe 6 , Sta 13 ]-BN(6−14) connected with the fluorescent dye, BDP-FL), were synthesized and tested in vitro with PCa and BCa cell lines, more specifically, with PCa cells, PC-3 and LNCaP, with BCa cells, T47D, MDA-MB-231, and with the in-house created PSMAoverexpressing PC-3 (PSMA) , T47D (PSMA) , and MDA-MB-231 (PSMA) . In addition, biomolecular simulations were conducted on the association of 1 and 2 with PSMA and GRPR. The PSMA overexpression resulted in an increase of cell-bound radioligand [ 68 Ga]Ga-1 (PSMA) for PCa and BCa cells and also of [ 68 Ga]Ga-2 (GRPR), especially in those cell lines already expressing GRPR. The results were confirmed by fluorescence-activated cell sorting with a PE-labeled PSMA-specific antibody and the fluorescence tracer 3. The docking calculations and molecular dynamics simulations showed how 1 enters the PSMA funnel region and how pharmacophore Glu-urea-Lys interacts with the arginine patch, the S1′, and S1 subpockets by forming hydrogen and van der Waals bonds. The chelating moiety of 1, that is, HBED-CC, forms additional stabilizing hydrogen bonding and van der Waals interactions in the arenebinding site. Ligand 2 is diving into the GRPR transmembrane (TM) helical cavity, thereby forming hydrogen bonds through its amidated end, water-mediated hydrogen bonds, and π−π interactions. Our results provide valuable information regarding the molecular mechanisms involved in the interactions of 1 and 2 with PSMA and GRPR, which might be useful for the diagnostic imaging and therapy of PCa and BCa.

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Radiolabeled PSMA Inhibitors

Cited by 24 publications

References 245 publications

[89Zr]Zr-PSMA-617 PET/CT in biochemical recurrence of prostate cancer: first clinical experience from a pilot study including biodistribution and dose estimates

[89Zr]Zr-PSMA-617 PET/CT in biochemical recurrence of prostate cancer: first clinical experience from a pilot study including biodistribution and dose estimates

Diagnostic Accuracy of PET/CT or PET/MRI Using PSMA-Targeting Radiopharmaceuticals in High-Grade Gliomas: A Systematic Review and a Bivariate Meta-Analysis

Investigation of Tumor Cells and Receptor-Ligand Simulation Models for the Development of PET Imaging Probes Targeting PSMA and GRPR and a Possible Crosstalk between the Two Receptors

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