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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
| Chemical name: | 111In-Tetrameric Plectin-1 targeting peptide (4(βAKTLLPTP-GGS(PEG5000))KKK-111In-DOTA-βA-NH2) | |
| Abbreviated name: | 111In-tPTP | |
| Synonym: | 111In-Tetrameric Plectin-1 targeting peptide | |
| Agent category: | Peptide | |
| Target: | Plectin-1 | |
| Target category: | Receptor | |
| Method of detection: | Single-photon emission computed tomography (SPECT), gamma imaging | |
| Source of signal\contrast: | 111In | |
| Activation: | No | |
| Studies: |
| Click on protein, nucleotide (RefSeq), and gene for more information about Plectin-1. |
In vitro
Background
[PubMed]
Patients with pancreatic ductal adenocarcinoma (PDAC) have a median survival of 6 months and a 5-year survival rate of only 3% (1). PDAC is an aggressive cancer with early metastasis in >80% of patients. Early detection would be particularly useful for monitoring people at high risk of developing pancreatic cancer. Plectin-1 was identified in 100% of tested PDAC lesions and 60% of tested preinvasive PanIN III lesions (2). Plectin-1, a cytoskeletal component, is not expressed in the normal pancreas, liver, lymph node, lung, or peritoneum in humans. Using phage display screenings, the linear peptide Lys-Thr-Leu-Leu-Pro-Thr-Pro (KTLLPTP) (Plectin-1–targeting peptide, PTP) (3) has been found to specifically bind to Plectin-1 (4, 5), a protein present both inside and on the membrane of human and mouse PDAC cells but only on the inside of normal pancreatic cells. Kelly et al. (3) conjugated PTP to Cy5.5-labeled cross-linked iron oxide particles (CLIO-Cy5.5) for imaging Plectin-1 expression in PDAC, which suggests that Plectin-1 can serve as a biomarker for PDAC. Bausch et al. (2) labeled a tetrameric PTP with 111In (4(βAKTLLPTP-GGS(PEG5000))KKK-111In-DOTA-βA-NH2) (111In-tPTP) for single-photon emission computed tomography (SPECT) imaging for primary and metastatic pancreatic tumors.
Synthesis
[PubMed]
4(βAKTLLPTP-GGS(PEG5000))KKK-DOTA-βA-NH2 (tPTP) (100 µg) was incubated with 185 MBq (5 mCi) 111InCl3 in ammonium acetate buffer (pH 4.5) for 15 min at 40°C (2). 111In-tPTP was purified with column chromatography. The yield, radiochemical purity, and specific activity of 111In-tPTP were not reported.
In Vitro Studies: Testing in Cells and Tissues
[PubMed]
Competition binding assays were performed in Plectin-1–positive L3.6pl PDAC cells using 111In-tPTP with tPTP. tPTP had a Ki value of 830 nM (2).
Animal Studies
Rodents
[PubMed]
Bausch et al. (2) performed ex vivo biodistribution studies in mice bearing orthotopically implanted L3.6pl (n = 10), Panc1 (n = 5), or AK134 (n = 8) PDAC tumor cells at 4 h after injection of 37 MBq (1 mCi) 111In-tPTP. Tumor accumulation of radioactivity was 2.0% injected dose per gram (ID/g), 1.8% ID/g, 1.5% ID/g, and 0.5% ID/g for L3.6pl, Panc1, AK134, and normal pancreas, respectively. Accumulation in these mice was highest in the kidney with 15%–22% ID/g, followed by the liver with 1.7%–2.6% ID/g. Immunohistochemistry of sections of the pancreas and peritoneum metastases confirmed the presence of Plectin-1–expressing tumor cells in the pancreas and peritoneum.
SPECT scanning clearly visualized the three tumors and the kidneys at 4 h after injection. SPECT scanning located metastases in the peritoneum of two mice, which were confirmed with autopsy. In a model of AK134 PDAC liver metastasis, SPECT/computed tomography scanning clearly identified tumor lesions in the liver, which were confirmed with autopsy.
NIH Support
R01 CA137071-02, R01 CA137071-04, R01 EB010023-01A1, R01 EB010023-02
References
- 1.
- Li D., Xie K., Wolff R., Abbruzzese J.L. Pancreatic cancer. Lancet. 2004;363(9414):1049–57. [PubMed: 15051286]
- 2.
- Bausch D., Thomas S., Mino-Kenudson M., Fernandez-del C.C., Bauer T.W., Williams M., Warshaw A.L., Thayer S.P., Kelly K.A. Plectin-1 as a novel biomarker for pancreatic cancer. Clin Cancer Res. 2011;17(2):302–9. [PMC free article: PMC3044444] [PubMed: 21098698]
- 3.
- Kelly K.A., Bardeesy N., Anbazhagan R., Gurumurthy S., Berger J., Alencar H., Depinho R.A., Mahmood U., Weissleder R. Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma. PLoS Med. 2008;5(4):e85. [PMC free article: PMC2292750] [PubMed: 18416599]
- 4.
- Andra K., Kornacker I., Jorgl A., Zorer M., Spazierer D., Fuchs P., Fischer I., Wiche G. Plectin-isoform-specific rescue of hemidesmosomal defects in plectin (-/-) keratinocytes. J Invest Dermatol. 2003;120(2):189–97. [PubMed: 12542521]
- 5.
- Sonnenberg A., Liem R.K. Plakins in development and disease. Exp Cell Res. 2007;313(10):2189–203. [PubMed: 17499243]
- Review Lys-Thr-Leu-Leu-Pro-Thr-Pro-cross-linked iron oxide-Cy5.5.[Molecular Imaging and Contrast...]Review Lys-Thr-Leu-Leu-Pro-Thr-Pro-cross-linked iron oxide-Cy5.5.Leung K. Molecular Imaging and Contrast Agent Database (MICAD). 2004
- Plectin-1 as a novel biomarker for pancreatic cancer.[Clin Cancer Res. 2011]Plectin-1 as a novel biomarker for pancreatic cancer.Bausch D, Thomas S, Mino-Kenudson M, Fernández-del CC, Bauer TW, Williams M, Warshaw AL, Thayer SP, Kelly KA. Clin Cancer Res. 2011 Jan 15; 17(2):302-9. Epub 2010 Nov 23.
- Optical magnetic multimodality imaging of plectin-1-targeted imaging agent for the precise detection of orthotopic pancreatic ductal adenocarcinoma in mice.[EBioMedicine. 2022]Optical magnetic multimodality imaging of plectin-1-targeted imaging agent for the precise detection of orthotopic pancreatic ductal adenocarcinoma in mice.Zhang W, Liang X, Zhu L, Zhang X, Jin Z, Du Y, Tian J, Xue H. EBioMedicine. 2022 Jun; 80:104040. Epub 2022 May 4.
- Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.[PLoS Med. 2008]Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.Kelly KA, Bardeesy N, Anbazhagan R, Gurumurthy S, Berger J, Alencar H, Depinho RA, Mahmood U, Weissleder R. PLoS Med. 2008 Apr 15; 5(4):e85.
- Review Bombesin peptide conjugated–cross-linked iron oxide-Cy5.5.[Molecular Imaging and Contrast...]Review Bombesin peptide conjugated–cross-linked iron oxide-Cy5.5.The MICAD Research Team. Molecular Imaging and Contrast Agent Database (MICAD). 2004
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