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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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IRDye800-2-(3-{5-[7-(5-amino-1-carboxy-pentylcarbamoyl)-heptanoylamino]-1-carboxy-pentyl}-ureido)-pentanedioic acid

YC-27
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: July 7, 2010.

Chemical name:IRDye800-2-(3-{5-[7-(5-amino-1-carboxy-pentylcarbamoyl)-heptanoylamino]-1-carboxy-pentyl}-ureido)-pentanedioic acid
Abbreviated name:YC-27
Synonym:
Agent category:Compound
Target:Prostate-specific membrane antigen (PSMA), or N-acetyl α-linked acidic dipeptidase (NAALADase)
Target category:Antigen
Method of detection:Optical, near-infrared fluorescence (NIR) imaging
Source of signal:IRDye 800CW
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about PSMA.

Background

[PubMed]

Optical fluorescence imaging is increasingly being used to monitor biological functions of specific targets in small animals (1-4). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350–650 nm) are used. Near-infrared (NIR) fluorescence (650–1,000 nm) detection avoids the natural background fluorescence interference of biomolecules, providing a high contrast between target and background tissues in small animals. NIR fluorophores have a wider dynamic range and minimal background fluorescence as a result of reduced scattering compared with visible fluorescence detection. NIR fluorophores also have high sensitivity, attributable to low background fluorescence, and high extinction coefficients, which provide high quantum yields. The NIR region is also compatible with solid-state optical components, such as diode lasers and silicon detectors. NIR fluorescence imaging is a non-invasive complement to radionuclide imaging in small animals (4, 5).

Prostate-specific membrane antigen (PSMA) is a cell-surface glycoprotein with a molecular weight of ~100 kDa. It is a unique, type II, transmembrane-bound glycoprotein that is overexpressed on prostate tumor cells and in the neovasculature of most solid prostate tumors, but not in the vasculature of normal tissues (6, 7). PSMA has also been detected in other tissues such as the kidneys, the proximal small intestine, and the salivary glands (7). PSMA was found to have N-acetyl α-linked acidic dipeptidase (NAALADase) or glutamate carboxypeptidase II activity (8). PSMA may play an important role in the progression of prostate cancer and glutamatergic neurotransmission, as well as in the absorption of folate (9). In the central nervous system, PSMA metabolizes N-acetyl-aspartyl-glutamate, and in the proximal small intestine it removes γ-linked glutamates from poly-γ-glutamate folate and folate hydrolase (7). PSMA can be used as a marker for the detection of metastatic cancers with imaging agents. Although a commercially available monoclonal antibody (111In-labeled Capromomab pendetide (111In-CYT-356)) is in clinical use for the detection of prostate cancer, the results obtained with this antibody are not entirely reliable (10). In addition, this antibody has limited access to tumors and may produce low signal/noise ratios because the target is the intracellular domain of PSMA (11, 12). 2-(3-{5-[7-(5-Amino-1-carboxy-pentylcarbamoyl)-heptanoylamino]-1-carboxy-pentyl}-ureido)-pentanedioic acid (compound 2) was conjugated with IRDye800CW to form IRDye800CW-2 (YC-27) (13), which is an inhibitor of NAALADase. YC-27 has been studied for use as an NIR agent for imaging PSMA expression in nude mice bearing human cancer xenografts.

Synthesis

[PubMed]

To a solution of 430 nmol compound 2 in dimethyl sulfoxide was added 0.0114 mM N,N-diisopropylethylamine, followed by N-hydroxysuccininide ester of IRDye800CW (13). The mixture was incubated at room temperature for 2 h. YC-27 was purified with high-performance liquid chromatography. The molecular weight of YC-27 (1.59 kDa) was confirmed with mass spectroscopy. YC-27 exhibited an absorbance maximum at 774 nm and an emission maximum at 792 nm with an extinction coefficient of 158,900 M-1 and a fluorescence quantum yield of 0.053 in aqueous solution.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

The binding affinity of YC-27 for PSMA was determined with the use of a NAALADase assay (13). YC-27 exhibited an inhibition constant (Ki) value of 0.37 nM. The Ki value of the known urea-based NAAG peptidase inhibitor ZJ-43 was 2.1 nM.

Animal Studies

Rodents

[PubMed]

Chen et al. (13) performed NIR fluorescence imaging studies of YC-27 (10 nmol) in nude mice (n = 3) bearing PSMA-positive PC3-PIP tumor xenografts and PSMA-negative PC3-flu tumor xenografts. The PC3-PIP tumors were clearly visualized at 18 h and up to 70.5 h after injection. On the other hand, the NIR signal from the PC3-flu tumors was weak. The PC3-PIP/PC3-flu ratio was 10 at 70.5 h. Moderate NIR fluorescence was visualized in the kidneys. Co-injection of 1 nmol YC-27 with 1,000 nmol DClBzL (PSMA inhibitor) in mice bearing the two tumors inhibited the NIR fluorescence in the PC3-PIP tumors and kidneys nearly to the background level of the PC3-flu tumors at 20.5 h after injection. The PC3-PIP/PC3-flu ratio was 26 at 20.5 h. The NIR signals in the tumors and kidneys were also confirmed with ex vivo imaging.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

NIH Support

U24 CA92871, R01 CA134675

References

1.
Achilefu S. Lighting up tumors with receptor-specific optical molecular probes. Technol Cancer Res Treat. 2004;3(4):393–409. [PubMed: 15270591]
2.
Ntziachristos V., Bremer C., Weissleder R. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur Radiol. 2003;13(1):195–208. [PubMed: 12541130]
3.
Becker A., Hessenius C., Licha K., Ebert B., Sukowski U., Semmler W., Wiedenmann B., Grotzinger C. Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands. Nat Biotechnol. 2001;19(4):327–31. [PubMed: 11283589]
4.
Leung K., Chopra A., Shan L., Eckelman W.C., Menkens A.E. Essential parameters to consider for the characterization of optical imaging probes. Nanomedicine (Lond) 2012;7(7):1101–7. [PMC free article: PMC3445333] [PubMed: 22846094]
5.
Tung C.H. Fluorescent peptide probes for in vivo diagnostic imaging. Biopolymers. 2004;76(5):391–403. [PubMed: 15389488]
6.
Feneley M.R., Jan H., Granowska M., Mather S.J., Ellison D., Glass J., Coptcoat M., Kirby R.S., Ogden C., Oliver R.T., Badenoch D.F., Chinegwundoh F.I., Nargund V.H., Paris A.M., Britton K.E. Imaging with prostate-specific membrane antigen (PSMA) in prostate cancer. Prostate Cancer Prostatic Dis. 2000;3(1):47–52. [PubMed: 12497162]
7.
Ghosh A., Heston W.D. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004;91(3):528–39. [PubMed: 14755683]
8.
Luthi-Carter R., Barczak A.K., Speno H., Coyle J.T. Molecular characterization of human brain N-acetylated alpha-linked acidic dipeptidase (NAALADase). J Pharmacol Exp Ther. 1998;286(2):1020–5. [PubMed: 9694964]
9.
O'Keefe D.S., Uchida A., Bacich D.J., Watt F.B., Martorana A., Molloy P.L., Heston W.D. Prostate-specific suicide gene therapy using the prostate-specific membrane antigen promoter and enhancer. Prostate. 2000;45(2):149–57. [PubMed: 11027414]
10.
Ponsky L.E., Cherullo E.E., Starkey R., Nelson D., Neumann D., Zippe C.D. Evaluation of preoperative ProstaScint scans in the prediction of nodal disease. Prostate Cancer Prostatic Dis. 2002;5(2):132–5. [PubMed: 12497003]
11.
Sundaresan G., Yazaki P.J., Shively J.E., Finn R.D., Larson S.M., Raubitschek A.A., Williams L.E., Chatziioannou A.F., Gambhir S.S., Wu A.M. 124I-labeled engineered anti-CEA minibodies and diabodies allow high-contrast, antigen-specific small-animal PET imaging of xenografts in athymic mice. J Nucl Med. 2003;44(12):1962–9. [PMC free article: PMC4167879] [PubMed: 14660722]
12.
Jain R.K. Transport of molecules, particles, and cells in solid tumors. Annu Rev Biomed Eng. 1999;1:241–63. [PubMed: 11701489]
13.
Chen Y., Dhara S., Banerjee S.R., Byun Y., Pullambhatla M., Mease R.C., Pomper M.G. A low molecular weight PSMA-based fluorescent imaging agent for cancer. Biochem Biophys Res Commun. 2009;390(3):624–9. [PMC free article: PMC2787846] [PubMed: 19818734]

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