scholarly journals 68Ga-labeled ODAP-Urea-based PSMA Agents in Prostate Cancer: First-in-human Imaging of an Optimized Agent

2021 ◽  
Author(s):  
Xiaojiang Duan ◽  
Zhen Cao ◽  
Hua Zhu ◽  
Chen Liu ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Human Study ◽  
Radiochemical Yield ◽  
Cell Uptake ◽  
Normal Organ ◽  
Promising Target ◽  
Pharmacokinetic Properties ◽  
Xenograft Models ◽  
Specific Membrane ◽  
Yield And Purity

Abstract Purpose: Prostate-specific membrane antigen (PSMA) is a promising target for prostate cancer imaging and therapy. The most commonly used scaffold incorporates a glutamate-urea (Glu-Urea) function. We recently developed oxalyldiaminopropionic acid-urea (ODAP-Urea) PSMA ligands in an attempt to improve upon the pharmacokinetic properties of existing agents. Here we report the synthesis of an optimized 68 Ga-labeled ODAP-Urea-based ligand, [ 68 Ga]Ga-P 137 , and first-in-human results. Methods: Twelve ODAP-Urea-based ligands were synthesized and radiolabeled with 68 Ga in high radiochemical yield and purity. Their PSMA inhibitory capacities were determined using the NAALADase assay. Radioligands were evaluated in mice bearing 22Rv1 prostate tumors by microPET. Lead compound [ 68 Ga]Ga-P 137 was evaluated for stability, cell uptake and biodistribution. PET imaging of [ 68 Ga]Ga-P 137 was performed in three patients head-to-head compared to [ 68 Ga]Ga-PSMA-617. Results : Ligands were synthesized in 11.1%-44.4% yield and >95% purity. They have high affinity to PSMA( K i of 0.13 NM to 5.47 nM). [ 68 Ga]Ga-P 137 was stable and hydrophilic. [ 68 Ga]Ga-P 137 showed higher uptake than [ 68 Ga]Ga-PSMA-617 in tumor-bearing mice at 6.43 ± 0.98 %ID/g vs 3.41 ± 1.31 %ID/g at 60 min post-injection. In humans studies, the normal organ biodistribution of [ 68 Ga]Ga-P 137 was grossly equivalent to that of [ 68 Ga]Ga-PSMA-617 except for within the urinary tract, in which [ 68 Ga]Ga-P 137 demonstrated lower uptake. Conclusion: The optimized ODAP-Urea-based ligand [ 68 Ga]Ga-P 137 can image PSMA in xenograft models and humans, with lower bladder accumulation to the Glu-Urea-based agent, [ 68 Ga]Ga-PSMA-617, in a preliminary, first-in-human study.

PSMA-targeted melanin-like nanoparticles as a multifunctional nanoplatform for prostate cancer theranostics

2021 ◽  
Author(s):  
Liqun Dai ◽  
Guohua Shen ◽  
Peng Yang ◽  
Hong Wang ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Cancer Imaging ◽  
Prostate Tumor ◽  
Prostate Specific Membrane Antigen ◽  
Promising Target ◽  
Prostate Tumor Cells ◽  
Cancer Theranostics ◽  
Specific Membrane

Prostate-specific membrane antigen (PSMA) is highly expressed on the surface of most prostate tumor cells and is considered a promising target for prostate cancer imaging and treatment. It is possible...

scholarly journals On Site Production of [18F]-PSMA1007 Using Different [18F]-fluoride Activities. Practical, Technical and Economical Impact.

2021 ◽  
Author(s):  
Costantina Maisto ◽  
Anna Morisco ◽  
Roberta de Marino ◽  
Squame Elisabetta ◽  
Valentina Porfidia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Large Scale ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Good Target ◽  
Pet Ct ◽  
Fetal Bovine ◽  
Imaging Properties ◽  
Specific Membrane ◽  
Psma Inhibitor

Abstract BackgroundProstate-Specific Membrane Antigen is overexpressed in prostate cancer and it is considered a good target for staging of primary and recurrences as well as for radioligand therapy. Different PSMA-analogues have been investigated, labeled with [68Ga], showing excellent imaging properties; although, only small amounts can be produced for single synthesis. Recently, a fluorinated PSMA-inhibitor, [18F]-PSMA-1007, has been introduced, ensuring large-scale productions. In this study, the radiosynthesis of [18F]-PSMA-1007 using low (A), medium (B) and high (C) starting activities of [18F]-Fluoride, has been fully tested. The following parameters radiochemical yield, radiochemical purity and stability of [18F]-PSMA-1007 have been measured in 65, consecutive batches to verify the effects of the three different conditions. In addition, the analysis of the costs for the production has been performed. ResultsThe radiochemical yield percentage for low and medium range of activities of [18F]-Fluoride was 52%, while for the high range it decreases to 40%. The radiochemical purity was 99% in all three tested starting activities. [18F]-PSMA-1007 did not show radiolysis up to 8 hours after the end of synthesis, confirming that the radiopharmaceutical is stable an suitable for PET studies in humans. Furthermore, stability studies performed in fetal bovine serum demonstrated radiochemical stability at 37°C for 120’. ConclusionsA starting activity of [18F]-Fluoride of 90 GBq (range B) enables a final amount of [18F]-PSMA-1007 of about 50 GBq, which is powerful for different choices: to perform up to 25 PET/CT scans in a referral institution for prostate cancer, and/or to supply the eventual peripheral PET centers.

scholarly journals PSMA Theranostics: Current Status and Future Directions

2018 ◽  
Vol 17 ◽  
pp. 153601211877606 ◽  
Author(s):  
Kambiz Rahbar ◽  
Ali Afshar-Oromieh ◽  
Hossein Jadvar ◽  
Hojjat Ahmadzadehfar
Keyword(s):  
Prostate Cancer ◽  
Current Status ◽  
Castration Resistant Prostate Cancer ◽  
Future Directions ◽  
Castration Resistant ◽  
Promising Target ◽  
Challenges And Opportunities ◽  
Low Toxicity ◽  
Patient Selection Criteria ◽  
Specific Membrane

Prostate-specific membrane antigen (PSMA) is a promising target for imaging diagnostics and targeted radionuclide therapy (theranostics) of prostate cancer and its metastases. There is increasing evidence of encouraging response rates and a low toxicity profile of radioligand therapy (RLT) of metastatic castration-resistant prostate cancer using 177Lu-labeled PSMA ligands. In this article, we review the current status of diagnostics and therapy using radiolabeled PSMA ligands. We also suggest protocols for patient selection criteria and conduct of PSMA-based RLT. Challenges and opportunities of PSMA theranostics are discussed.

479: Prostate-Specific Membrane Antigen (PSMA) Expression as a Predictor of Prostate Cancer Progression

2006 ◽  
Vol 175 (4S) ◽  
pp. 155-156
Author(s):  
Matthias D. Hofer ◽  
Sven Perner ◽  
Haojie Li ◽  
Rainer Kuefer ◽  
Richard E. Hautmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Specific Membrane Antigen ◽  
Prostate Cancer Progression ◽  
Specific Membrane ◽  
Psma Expression

Hispidulin inhibits proliferation, migration, and invasion by promoting autophagy via regulation of PPARγ activation in prostate cancer cells and xenograft models

2020 ◽  
Author(s):  
Yuanyuan Wang ◽  
Shanqi Guo ◽  
Yingjie Jia ◽  
Xiaoyu Yu ◽  
Ruiyu Mou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Flavonoid Compound ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Invasion And Migration ◽  
Beneficial Effects ◽  
Anticancer Properties ◽  
Xenograft Models ◽  
And Migration

ABSTRACT Prostate cancer (PCa) is one of the important factors of cancer deaths especially in the western countries. Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid compound proved to possess anticancer properties, but its effects on PCa are left to be released. The aims of this study were to investigate the effects and the relative mechanisms of Hispidulin on PCa development. Hispidulin administration inhibited proliferation, invasion, and migration, while accelerated apoptosis in Du145 and VCaP cells, which was accompanied by PPARγ activation and autophagy enhancement. The beneficial effects of Hispidulin could be diminished by PPARγ inhibition. Besides, Hispidulin administration suppressed PCa tumorigenicity in Xenograft models, indicating the anticancer properties in vivo. Therefore, our work revealed that the anticancer properties of Hispidulin might be conferred by its activation on PPARγ and autophagy.

scholarly journals [18F]F-PSMA-1007 Radiolabelling without an On-Site Cyclotron: A Quality Issue

2021 ◽  
Vol 14 (7) ◽  
pp. 599
Author(s):  
Valentina Di Iorio ◽  
Stefano Boschi ◽  
Anna Sarnelli ◽  
Cristina Cuni ◽  
David Bianchini ◽  
...  
Keyword(s):  
Quality Assurance ◽  
Radiochemical Purity ◽  
Competent Authority ◽  
Radiochemical Yield ◽  
Synthesis Process ◽  
Control Parameters ◽  
Quality Issue ◽  
Assurance System ◽  
Quality Control Parameters ◽  
Specific Membrane

Radiopharmaceuticals targeting the prostate-specific membrane antigen (PSMA) has become the gold standard for PET imaging of prostate cancer. [68Ga]Ga-PSMA-11 has been the forerunner but a [18F]F-PSMA ligand has been developed because of the intrinsic advantages of Fluorine-18. Fluorine-18 labelled compounds are usually prepared in centers with an on-site cyclotron. Since our center has not an on-site cyclotron, we decided to verify the feasibility of producing the experimental 18F-labelled radiopharmaceutical [18F]F-PSMA-1007 with [18F]F- from different external suppliers. A quality agreement has been signed with two different suppliers, and a well-established and correctly implemented quality assurance protocol has been followed. The [18F]F- was produced with cyclotrons, on Nb target, but with different beam energy and current. Extensive validation of the [18F]F-PSMA-1007 synthesis process has been performed. The aim of this paper was the description of all the quality documentation which allowed the submission and approval of the Investigational Medicinal Product Dossier (IMPD) to the Competent Authority, addressing the quality problems due to different external suppliers. The result indicates that no significant differences have been found between the [18F]F- from the two suppliers in terms of radionuclidic and radiochemical purity and [18F]F- impacted neither the radiochemical yield of the labelling reaction nor the quality control parameters of the IMP [18F]F-PSMA-1007. These results prove how a correct quality assurance system can overcome some Regulatory Authorities issue that may represent an obstacle to the clinical use of F-18-labelled radiopharmaceuticals without an on-site cyclotron

scholarly journals 225Actinium-labeled prostate-specific membrane antigen targeting peptide induces complete response in a metastatic prostate cancer patient

2021 ◽  
Vol 10 (5) ◽  
pp. 205846012110225
Author(s):  
Omer Aras ◽  
Stefan Harmsen ◽  
Richard Ting ◽  
Haluk B Sayman
Keyword(s):  
Prostate Cancer ◽  
Standard Of Care ◽  
Complete Response ◽  
Prostate Specific Membrane Antigen ◽  
Limited Data ◽  
Castrate Resistant Prostate Cancer ◽  
Targeting Peptide ◽  
Castrate Resistant ◽  
Specific Membrane

Targeted radionuclide therapy has emerged as a promising and potentially curative strategy for high-grade prostate cancer. However, limited data are available on efficacy, quality of life, and pretherapeutic biomarkers. Here, we highlight the case of a patient with prostate-specific membrane antigen (PSMA)-positive metastatic castrate-resistant prostate cancer who displayed complete response to 225Ac-PSMA-617 after having been resistant to standard-of-care therapy, then initially partially responsive but later resistant to subsequent immunotherapy, and resistant to successive 177Lu-PSMA-617. In addition, the patient’s baseline germline mutation likely predisposed him to more aggressive disease.

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