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Evaluation of Novel Prostate-Specific Membrane Antigen-Targeted Near-Infrared Imaging Agent for Fluorescence-Guided Surgery of Prostate Cancer
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| Zeitschriftentitel: | Clinical Cancer Research |
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| Personen und Körperschaften: | , , , , , , |
| In: | Clinical Cancer Research, 25, 2019, 1, S. 177-187 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>The ability to locate and remove all malignant lesions during radical prostatectomy leads not only to prevent biochemical recurrence (BCR) and possible side effects but also to improve the life expectancy of patients with prostate cancer. Fluorescence-guided surgery (FGS) has emerged as a technique that uses fluorescence to highlight cancerous cells and guide surgeons to resect tumors in real time. Thus, development of tumor-specific near-infrared (NIR) agents that target biomarkers solely expressed on prostate cancer cells will enable to assess negative tumor margins and affected lymph nodes.</jats:p> </jats:sec> <jats:sec> <jats:title>Experimental Design:</jats:title> <jats:p>Because PSMA is overexpressed in prostate cancer cells in &gt;90% of the prostate cancer patient population, a prostate-specific membrane antigen (PSMA)-targeted NIR agent (OTL78) was designed and synthesized. Optical properties, in vitro and in vivo specificity, tumor-to-background ratio (TBR), accomplishment of negative surgical tumor margins using FGS, pharmacokinetics (PKs) properties, and preclinical toxicology of OTL78 were then evaluated in requisite models.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>OTL78 binds to PSMA-expressing cells with high affinity, concentrates selectively to PSMA-positive cancer tissues, and clears rapidly from healthy tissues with a half-time of 17 minutes. It also exhibits an excellent TBR (5:1) as well as safety profile in animals.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>OTL78 is an excellent tumor-specific NIR agent for use in fluorescence-guided radical prostatectomy and FGS of other cancers.</jats:p> </jats:sec> |
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| Umfang: | 177-187 |
| ISSN: |
1078-0432
1557-3265 |
| DOI: | 10.1158/1078-0432.ccr-18-0803 |