PD16-11 COMPARISON OF PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA)-TARGETED RADIONUCLIDE THERAPY (TRT) WITH LUTETIUM-177 (177LU) VIA ANTIBODY J591 VS SMALL MOLECULE LIGAND PSMA-617

The aim of this study was to analyze the required absorbed doses to detectable metastases (Dreq) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4–6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The Dreq was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The Dreq for iodine-131 and yttrium-90 was high (920–3300 Gy). The Dreq for lutetium-177 was between 560 and 780 Gy and considerably lower Dreq were obtained for actinium-225 and terbium-161, with 240–330 Gy and 210–280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands.

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The Future of PSMA-Targeted Radionuclide Therapy: An Overview of Recent Preclinical Research

Pharmaceutics ◽

10.3390/pharmaceutics11110560 ◽

2019 ◽

Vol 11 (11) ◽

pp. 560 ◽

Cited By ~ 6

Author(s):

Eline A.M. Ruigrok ◽

Wytske M. van Weerden ◽

Julie Nonnekens ◽

Marion de Jong

Keyword(s):

Radionuclide Therapy ◽

Therapeutic Strategies ◽

Prostate Specific Membrane Antigen ◽

Targeted Radionuclide Therapy ◽

Tumor Uptake ◽

Research Projects ◽

Major Focus ◽

Preclinical Research ◽

Specific Membrane ◽

Focus Point

Prostate specific membrane antigen (PSMA) has become a major focus point in the research and development of prostate cancer (PCa) imaging and therapeutic strategies using radiolabeled tracers. PSMA has shown to be an excellent target for PCa theranostics because of its high expression on the membrane of PCa cells and the increase in expression during disease progression. Therefore, numerous PSMA-targeting tracers have been developed and (pre)clinically studied with promising results. However, many of these PSMA-targeting tracers show uptake in healthy organs such as the salivary glands, causing radiotoxicity. Furthermore, not all patients respond to PSMA-targeted radionuclide therapy (TRT). This created the necessity of additional preclinical research studies in which existing tracers are reevaluated and new tracers are developed in order to improve PSMA-TRT by protecting the (PSMA-expressing) healthy organs and improving tumor uptake. In this review we will give an overview of the recent preclinical research projects regarding PCa-TRT using PSMA-specific radiotracers, which will give an indication of where the PSMA-TRT research movement is going and what we can expect in future clinical trials.

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Spotlight on PSMA as a new theranostic biomarker for bladder cancer

Scientific Reports ◽

10.1038/s41598-021-89160-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maria Maddalena Tumedei ◽

Sara Ravaioli ◽

Federica Matteucci ◽

Monica Celli ◽

Ugo De Giorgi ◽

...

Keyword(s):

Bladder Cancer ◽

Diagnostic Tests ◽

Radionuclide Therapy ◽

Tumor Type ◽

Prostate Specific Membrane Antigen ◽

Bladder Tissue ◽

Tissue Samples ◽

Specific Membrane ◽

Psma Expression ◽

Degree Of Extension

AbstractBladder cancer (BCa) patients are diagnosed by cytology and cystoscopy. However, these diagnostic tests bear some limitations. We sought for reliable biomarkers to better determine BCa extension. Prostate-specific membrane antigen (PSMA) appears to fulfill this requirement in prostate cancer but its role in BCa has not been established yet. We then analyzed 87 bladder tissue samples from 74 patients assessing PSMA expression by immunohistochemistry. The median PSMA expression, exclusively found in tumor neovasculature, in terms of H-score significantly differed between non-tumor samples and tumor samples (p = 0.00288) showing a higher neovasculature-related PSMA expression. No differences were observed in relation to tumor type, grade and stage. BCa neovasculature-related PSMA overexpression may be useful in defining the degree of extension of the neoplasm. In addition, testing PSMA expression by immunohistochemistry may hold theranostic implications both considering anti-angiogenesis agents and radio-labelled PSMA ligands for intracavitary radionuclide therapy. In our opinion, BCa neovasculature-related PSMA overexpression may be considered an apt target for anti-angiogenesis and radionuclide treatment in BCa, once the evaluation of tumor-retention time for the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment will be performed.

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Imaging of Prostate-Specific Membrane Antigen with Small-Molecule PET Radiotracers: From the Bench to Advanced Clinical Applications

Annual Review of Medicine ◽

10.1146/annurev-med-062117-073027 ◽

2019 ◽

Vol 70 (1) ◽

pp. 461-477 ◽

Cited By ~ 16

Author(s):

Steven P. Rowe ◽

Michael A. Gorin ◽

Martin G. Pomper

Keyword(s):

Small Molecules ◽

Small Molecule ◽

High Sensitivity ◽

Standard Of Care ◽

Prostate Specific Membrane Antigen ◽

Preclinical Development ◽

Positron Emission ◽

Definitive Therapy ◽

Pet Radiotracers ◽

Specific Membrane

In recent years, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) labeled with radionuclides that allow for positron emission tomography (PET) imaging have been extensively studied in many clinical contexts in men with prostate cancer (PCa). The high sensitivity and specificity of these agents for identifying sites of PCa has quickly led to their widespread adoption as a de facto clinical standard of care throughout much of the world. PSMA-targeted PET radiotracers have been particularly well-studied in preoperatively staging men with high-risk PCa, evaluating biochemical recurrence following definitive therapy, and guiding metastasis-directed therapy in patients suspected of having oligorecurrent/oligometastatic disease. Furthermore, the expression of PSMA on the tumor neovasculature of many nonprostate malignancies has enabled a burgeoning subfield concentrated on delineating the potential utility of PSMA-targeted PET agents for imaging other cancers. In this review, we highlight the preclinical development of key small molecules that are now being clinically utilized for PCa imaging, discuss the roles of PSMA-targeted agents in guiding patient management, and consider the role these compounds may play in imaging nonprostate cancers.

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