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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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Anti-human sperm protein 17 monoclonal antibody-indocyanine green derivative 02

Anti-Sp17-ICG-Der-02
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: December 20, 2012.

Chemical name:Anti-human sperm protein 17 monoclonal antibody-indocyanine green derivative 02
Abbreviated name:Anti-Sp17-ICG-Der-02
Synonym:ICG-Der-02-Anti-Sp17
Agent category:Antibody
Target:Sperm protein 17 (Sp17 or Spa17)
Target category:Antigen
Method of detection:Optical, near-infrared fluorescence (NIR) imaging
Source of signal:Indocyanine green derivative 02 (ICG-Der-02)
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about Sp17.

Background

[PubMed]

Optical fluorescence imaging is increasingly used to monitor biological functions of specific targets in small animals (1-3). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350–650 nm) are used. Near-infrared (NIR) fluorescence (650–900 nm) detection avoids the natural background fluorescence interference of biomolecules, providing a high contrast between target and background tissues. NIR fluorophores have wider dynamic range and minimal background fluorescence as a result of reduced scattering compared with visible fluorescence detection. They also have high sensitivity, resulting from 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 noninvasive complement to radionuclide imaging in small animals or with probes in close proximity to the target in humans (4). Among the various optical imaging agents, only indocyanine green (ICG), with NIR fluorescence absorption at 780 nm and emission at 820 nm, is approved by the United States Food and Drug Administration for clinical applications in angiography, blood flow evaluation, and liver function assessment (5-8). It is also under evaluation in several clinical trials for other applications, such as optical imaging and mapping of both the lymphatic vessels and lymph nodes in cancer patients for surgical dissection of tumor cells and endoscopic imaging of the pancreas and colon.

Sperm protein 17 (Sp17) is expressed exclusively in the testes, with its primary function of binding to the zona pellucida for fertilization (9). Expression of Sp17 in other normal tissues is limited. However, Sp17 was later found to be aberrantly expressed in various malignant tumors, such as myeloma, ovarian tumors, and esophageal squamous cell tumors (10, 11). Sp17 was expressed in 66% of endometrial tumors and 61% of cervical tumors (12). Li et al. (13) explored the overexpression of Sp17 in malignant tumors as a molecular biomarker for tumor imaging by coupling anti-human Sp17 monoclonal antibody with ICG derivative 02 (anti-Sp17-ICG-Der-02). ICG-Der-02 contains one carboxyl functional group for covalent conjugation to the amino group of biomolecules. ICG-Der-02 exhibits favorable water solubility and higher fluorescence quantum yield than ICG. Anti-Sp17-ICG-Der-02 was evaluated for in vivo NIR imaging of Sp17-positive human hepatocellular carcinoma cell line SMMC-7721 xenografts in mice.

Related Resource Links:

  • Chapters in MICAD (ICG, Sp17)
  • Gene information in NCBI (Sp17)
  • Articles in Online Mendelian Inheritance in Man (OMIM) (Sp17)
  • Clinical trials (ICG)
  • Drug information in FDA (ICG)

Synthesis

[PubMed]

Anti-Sp17 (clone 3C12, 1.3 nmol) was incubated with ICG-Der-02-N-hydroxysuccinimide ester (15 nmol) for 10 h at 4°C (13). Anti-Sp17-ICG-Der-02 was purified with dialysis. The absorption and emission peaks of anti-Sp17-ICG-Der-02 were at 780 nm and 835 nm, respectively. The absorption and emission peaks of ICG-Der-02 were at 780 nm and 810 nm, respectively. The immunoreactivity of anti-Sp17-ICG-Der-02 was ~60% compared with the unconjugated antibody. The number of ICG-Der-02 molecules per antibody was not reported.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Immunocytochemical analysis showed that anti-Sp17 mainly localized on the surface of cultured SMMC-7721 cells (Sp17-positive) but not on the surface of cells from the human ovarian cancer cell line HO8910 (Sp17-negative) (13).

Animal Studies

Rodents

[PubMed]

Tumor-imaging studies of anti-Sp17-ICG-Der-02 were performed in nude mice (n = 5) bearing SMMC-7721 tumors (13). Whole-body fluorescence images were obtained at 1 h and at 1, 2, 3, 5, and 7 d after intravenous injection of anti-Sp17-ICG-Der-02 (~6 nmol ICG-Der-02/mouse). Maximum NIR fluorescence signals in the tumors were obtained at 1 d after injection. Strong signal in the tumors was still observed at 7 d. On the other hand, ICG-Der-02 (n = 3) showed weak accumulation of NIR fluorescence signal in the tumors at 1 d and 2 d after injection. Both agents showed strong signals in the liver, kidney, and urinary bladder. Immunohistochemical analysis of the tumor sections showed that anti-Sp17 mainly localized on the cell surface and in the cytoplasm of the tumor tissues. No blocking studies with unconjugated anti-Sp17 were performed.

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.

Human Studies

Intramural Research Program

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.
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]
3.
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]
4.
Tung C.H. Fluorescent peptide probes for in vivo diagnostic imaging. Biopolymers. 2004;76(5):391–403. [PubMed: 15389488]
5.
Yannuzzi, L.A., Indocyanine green angiography: a perspective on use in the clinical setting. Am J Ophthalmol, 2011151(5): p. 745-751 e1. [PubMed: 21501704]
6.
Yamamoto M., Sasaguri S., Sato T. Assessing intraoperative blood flow in cardiovascular surgery. Surg Today. 2011;41(11):1467–74. [PubMed: 21969147]
7.
Schaafsma B.E., Mieog J.S., Hutteman M., van der Vorst J.R., Kuppen P.J., Lowik C.W., Frangioni J.V., van de Velde C.J., Vahrmeijer A.L. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol. 2011;104(3):323–32. [PMC free article: PMC3144993] [PubMed: 21495033]
8.
Manizate F., Hiotis S.P., Labow D., Roayaie S., Schwartz M. Liver functional reserve estimation: state of the art and relevance for local treatments: the Western perspective. J Hepatobiliary Pancreat Sci. 2010;17(4):385–8. [PubMed: 19936599]
9.
Wen Y., Richardson R.T., Widgren E.E., O'Rand M.G. Characterization of Sp17: a ubiquitous three domain protein that binds heparin. Biochem J. 2001;357(Pt 1):25–31. [PMC free article: PMC1221924] [PubMed: 11415432]
10.
De Jong A., Buchli R., Robbins D. Characterization of sperm protein 17 in human somatic and neoplastic tissue. Cancer Lett. 2002;186(2):201–9. [PubMed: 12213290]
11.
Li F.Q., Han Y.L., Liu Q., Wu B., Huang W.B., Zeng S.Y. Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells. BMC Cancer. 2009;9:323. [PMC free article: PMC2753635] [PubMed: 19744347]
12.
Li F.Q., Liu Q., Han Y.L., Wu B., Yin H.L. Sperm protein 17 is highly expressed in endometrial and cervical cancers. BMC Cancer. 2010;10:429. [PMC free article: PMC2931487] [PubMed: 20712874]
13.
Li F.Q., Zhang S.X., An L.X., Gu Y.Q. In vivo molecular targeting effects of anti-Sp17- ICG-Der-02 on hepatocellular carcinoma evaluated by an optical imaging system. J Exp Clin Cancer Res. 2011;30:25. [PMC free article: PMC3062613] [PubMed: 21366930]

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