Preclinical Evaluation of a Radiolabeled Anti-PSMA Dimeric Aptamer in a Murine Model of Human Prostate Cancer

Akesh Sinha; Darpan N. Pandya; Prabhakar Eeka; Olcay Boyacioglu; William H. Gmeiner; Thaddeus J. Wadas

doi:10.3390/molecules31030493

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Preclinical Evaluation of a Radiolabeled Anti-PSMA Dimeric Aptamer in a Murine Model of Human Prostate Cancer

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Preclinical Evaluation of a Radiolabeled Anti-PSMA Dimeric Aptamer in a Murine Model of Human Prostate Cancer

Akesh Sinha, Darpan N. Pandya, Prabhakar Eeka, Olcay Boyacioglu, William H. Gmeiner and Thaddeus J. Wadas

Molecules (Basel, Switzerland), Vol.31(3), 493

01/31/2026

DOI: 10.3390/molecules31030493

PMCID: PMC12899641

PMID: 41683470

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Abstract

Prostate cancer is the third-leading cause of cancer death in men. Prostate-specific membrane antigen (PSMA) is a robust biomarker that is expressed in approximately 80% of patients diagnosed with prostate cancer; several theranostic strategies have emerged based upon targeting this biomarker. This report describes a dimeric aptamer complex (DAC) which is selective for PSMA+ cancer cells and is amenable to derivatization with additional diagnostic and therapeutic molecules. Confocal microscopy confirmed the selective nature of the DAC for PSMA+ LNCAP tumor cells. In addition, the affinity of the DAC for the PSMA protein was determined to be 2.16 ± 0.15 nM using biolayer interferometry (BLI). In proof-of-principle studies, this DAC was biotinylated (BioDAC; A10), complexed with streptavidin (SA), and radiolabeled with the positron-emitting radioisotope zirconium-89 (89Zr: t½ = 78.4 h, β+: 22.8%) to form the radiopharmaceutical [89Zr]Zr-Df-SA-BioDAC ([89Zr]Zr-A12). Acute biodistribution studies revealed elevated levels of radioactivity in PSMA+ tumors when compared to PSMA− tumors. Radioactivity retention in the kidney was high due to the presence of streptavidin, while radioactivity retention in the liver was comparable with that of other radiolabeled aptamer complexes. Accordingly, the data suggests that the radiopharmaceutical will need to be redesigned using a strategy that is not reliant on a biotin–streptavidin paradigm before additional preclinical assessments are made and clinical translation can be attempted.

Prostate Cancer

Radiochemistry

aptamer

prostate-specific membrane antigen

zirconium-89

Details

Title: Subtitle: Preclinical Evaluation of a Radiolabeled Anti-PSMA Dimeric Aptamer in a Murine Model of Human Prostate Cancer
Creators: Akesh Sinha - University of Iowa
Darpan N. Pandya - University of Iowa
Prabhakar Eeka - University of Iowa
Olcay Boyacioglu - Adnan Menderes University
William H. Gmeiner - Wake Forest University
Thaddeus J. Wadas - University of Iowa
Resource Type: Journal article
Publication Details: Molecules (Basel, Switzerland), Vol.31(3), 493
DOI: 10.3390/molecules31030493
PMID: 41683470
PMCID: PMC12899641
NLM abbreviation: Molecules
ISSN: 1420-3049
eISSN: 1420-3049
Publisher: MDPI
Grant note: Fusion Energy Sciences (http://data.elsevier.com/vocabulary/SciValFunders/100006207) Wake Forest Innovations North Carolina Biotechnology Center (http://data.elsevier.com/vocabulary/SciValFunders/100005562) R21-CA227709 / National Cancer Institute, Cairo University (501100002387) Office of the Vice President for Research and Economic Development, University of Iowa (100011641) R21-CA227709 / National Computational Infrastructure (100010582) Nuclear Physics (http://data.elsevier.com/vocabulary/SciValFunders/100006209) Graduate College, University of Iowa (100012011) Roy J. and Lucille A. Carver College of Medicine, University of Iowa (100015515) North Carolina Biotechnology Center (100005562)
Language: English
Date published: 01/31/2026
Academic Unit: Radiology; Radiation Oncology
Record Identifier: 9985139273102771

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