Dataset Information

MRl of prostate cancer antigen expression for diagnosis and immunotherapy.

ABSTRACT:

Background

Tumor antigen (TA)-targeted monoclonal antibody (mAb) immunotherapy can be effective for the treatment of a broad range of cancer etiologies; however, these approaches have demonstrated variable clinical efficacy for the treatment of patients with prostate cancer (PCa). An obstacle currently impeding translational progress has been the inability to quantify the mAb dose that reaches the tumor site and binds to the targeted TAs. The coupling of mAb to nanoparticle-based magnetic resonance imaging (MRI) probes should permit in vivo measurement of patient-specific biodistributions; these measurements could facilitate future development of novel dosimetry paradigms wherein mAb dose is titrated to optimize outcomes for individual patients.

Methods

The prostate stem cell antigen (PSCA) is broadly expressed on the surface of prostate cancer (PCa) cells. Anti-human PSCA monoclonal antibodies (mAb 7F5) were bound to Au/Fe(3)O(4) (GoldMag) nanoparticles (mAb 7F5@GoldMag) to serve as PSCA-specific theragnostic MRI probe permitting visualization of mAb biodistribution in vivo. First, the antibody immobilization efficiency of the GoldMag particles and the efficacy for PSCA-specific binding was assessed. Next, PC-3 (prostate cancer with PSCA over-expression) and SMMC-7721 (hepatoma cells without PSCA expression) tumor-bearing mice were injected with mAb 7F5@GoldMag for MRI. MRI probe biodistributions were assessed at increasing time intervals post-infusion; therapy response was evaluated with serial tumor volume measurements.

Results

Targeted binding of the mAb 7F5@GoldMag probes to PC-3 cells was verified using optical images and MRI; selective binding was not observed for SMMC-7721 tumors. The immunotherapeutic efficacy of the mAb 7F5@GoldMag in PC-3 tumor-bearing mice was verified with significant inhibition of tumor growth compared to untreated control animals.

Conclusion

Our promising results suggest the feasibility of using mAb 7F5@GoldMag probes as a novel paradigm for the detection and immunotherapeutic treatment of PCa. We optimistically anticipate that the approaches have the potential to be translated into the clinical settings.

SUBMITTER: Ren J

PROVIDER: S-EPMC3384648 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

MRl of prostate cancer antigen expression for diagnosis and immunotherapy.

Ren Jing J Wang Fang F Wei Guangquan G Yang Yong Y Liu Ying Y Wei Mengqi M Huan Yi Y Larson Andrew C AC Zhang Zhuoli Z

PloS one 20120627 6

<h4>Background</h4>Tumor antigen (TA)-targeted monoclonal antibody (mAb) immunotherapy can be effective for the treatment of a broad range of cancer etiologies; however, these approaches have demonstrated variable clinical efficacy for the treatment of patients with prostate cancer (PCa). An obstacle currently impeding translational progress has been the inability to quantify the mAb dose that reaches the tumor site and binds to the targeted TAs. The coupling of mAb to nanoparticle-based magneti ...[more]

PMID: 22761679

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Project description:BackgroundProstate-specific membrane antigen (PSMA), overexpressed on prostate cancer (PCa), is a well-characterized cell surface protein to selectively diagnose PCa. PSMA's unique characteristics and its 1000-fold higher expression in PCa compared with other tissues renders it as a suitable biomarker for detection of PCa in its early stage. In this report, we critically analyze and recommend the requirements needed for the development of variety of PSMA-targeted molecular imaging agents based on antibodies, small molecule ligands, peptides, and aptamers. The targeting moieties are either conjugated to radionuclear isotopes or near-infrared agents for efficient diagnosis of PCa.Recent findingsFrom the analysis, it was found that several small molecule-derived PCa imaging agents are approved for clinical trials in Europe and the United States, and few are already in the clinical use for diagnosis of PCa. Even though 111In-labeled capromab pendetide was approved by the Food and Drug Administration (FDA) and other engineered antibodies are available for detection of PCa, but high production cost, low shelf life (less than 1 month at 4°C), possibility of human immuno reactions, and low blood clearance rate necessitated a need for developing new imaging agents, which are serum stable, cost-effective, and possesses longer shelf life (6 months), have fast clearance rate from nontargeted tissues during the diagnosis process. It is found that small molecule ligand-derived imaging agents possesses most of the desired properties expected for an ideal diagnostic agent when compared with other targeting moieties.ConclusionThis report discusses in detail the homing moieties used in the development of targeted diagnostic tools for detection of PCa. The merits and demerits of monoclonal antibodies, small molecule ligands, peptides, and aptamers for imaging of PCa and intraoperative guided surgery are extensively analyzed. Among all, urea-based ligands were found to be most successful in preclinical and clinical trials and show a major promise for future commercialization.

Dataset Information

MRl of prostate cancer antigen expression for diagnosis and immunotherapy.

Background

Methods

Results

Conclusion

Publications

MRl of prostate cancer antigen expression for diagnosis and immunotherapy.

Similar Datasets

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