Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice
Prostate cancer is the most frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterize...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Prostate Cancer |
| Online Access: | http://dx.doi.org/10.1155/2014/104248 |
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| author | Joy L. Kovar Lael L. Cheung Melanie A. Simpson D. Michael Olive |
| author_facet | Joy L. Kovar Lael L. Cheung Melanie A. Simpson D. Michael Olive |
| author_sort | Joy L. Kovar |
| collection | DOAJ |
| description | Prostate cancer is the most frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds. In vivo targeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy. In vitro and in vivo blocking studies confirmed YC-27 specificity. In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections. |
| format | Article |
| id | doaj-art-70106aae2ea345f7b45294019d9ea5e8 |
| institution | Kabale University |
| issn | 2090-3111 2090-312X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Prostate Cancer |
| spelling | doaj-art-70106aae2ea345f7b45294019d9ea5e82025-02-03T01:22:28ZengWileyProstate Cancer2090-31112090-312X2014-01-01201410.1155/2014/104248104248Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing MiceJoy L. Kovar0Lael L. Cheung1Melanie A. Simpson2D. Michael Olive3Translational Research, LI-COR Biosciences, 4647 Superior Street, Lincoln, NE 68504, USATranslational Research, LI-COR Biosciences, 4647 Superior Street, Lincoln, NE 68504, USADepartment of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664, USASVS Consulting, Lincoln, NE 68516, USAProstate cancer is the most frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds. In vivo targeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy. In vitro and in vivo blocking studies confirmed YC-27 specificity. In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections.http://dx.doi.org/10.1155/2014/104248 |
| spellingShingle | Joy L. Kovar Lael L. Cheung Melanie A. Simpson D. Michael Olive Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice Prostate Cancer |
| title | Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice |
| title_full | Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice |
| title_fullStr | Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice |
| title_full_unstemmed | Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice |
| title_short | Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice |
| title_sort | pharmacokinetic and biodistribution assessment of a near infrared labeled psma specific small molecule in tumor bearing mice |
| url | http://dx.doi.org/10.1155/2014/104248 |
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