NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

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

Cover of Molecular Imaging and Contrast Agent Database (MICAD)

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

Show details

99mTc-(NαHis)Ac-(Arg-N-CH3)-Arg-Pro-(dimethyl-Tyr)-(tertary-Leu)-Leu

99mTc-NT-XIX
, PhD
National Center for Biotechnology Information, NLM, NIH
Corresponding author.

Created: ; Last Update: September 18, 2009.

Chemical name:99mTc-(NαHis)Ac-(Arg-N-CH3)-Arg-Pro-(dimethyl-Tyr)-(tertary-Leu)-Leu
Abbreviated name:99mTc-NT-XIX
Synonym:
Agent category:Peptide
Target:Neurotensin receptors (NTRs)
Target category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT), gamma planar imaging
Source of signal\contrast:99mTc
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about neurotensin receptor 1.

Background

[PubMed]

Neurotensin (NT) is a tridecapeptide produced in the hypothalamus (1). It binds to NT receptors (NTRs) with high affinity and is implicated in the regulation of luteinizing hormone and prolactin release, and it has significant interaction with the dopaminergic system. There are three NTR subtypes, namely NTR1, NTR2, and NTR3. Most of the NT actions are mediated by NTR1, which is a G-protein–coupled receptor. The functions of NTR2 and NTR3 are not well known. The findings of NTR1 overexpression in various human tumors (2, 3), such as breast, lung, colon, pituitary, and pancreatic cancers, provide opportunities for tumor imaging by designing specific molecular imaging agents to target the NTR1.

NT is rapidly metabolized in plasma by proteinases (4). Several NT analogs have been developed by modifications of the amino acid cleavage sites of NT(8-13) to increase plasma stability (5, 6). Maes et al. (6) has identified a modified peptide, (NαHis)Ac-(Arg-N-CH3)-Arg-Pro-(dimethyl-Tyr)-(tertary-Leu)-Leu (NT-XIX), to be metabolically stable in plasma with good affinity for NTR1. 99mTc-Labeled NT-XIX (99mTc-NT-XIX) has been evaluated as a single-photon emission computed tomography (SPECT) imaging agent of NTR1 in nude mice bearing human colon adenocarcinoma HT-29 cells (5).

Synthesis

[PubMed]

A solution of 99mTc-pertechnetate, sodium boranocarbonate, borax, K-Na tartrate tetrahydrate, and sodium carbonate was heated for 20 min at 100°C (5). NT-XIX (20 nmol) was added to this cooled solution and heated for 60 min at 75°C. 99mTc-NT-XIX was purified with high-performance liquid chromatography. The labeling yield was >95%. The specific activity of the purified product was not reported. 99mTc-NT-XIX (0.2 pM) was >99% intact in human plasma after 24 h at 37°C with a half-life of 28 days.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Garcia-Garayoa et al. (5) performed in vitro internalization studies of 99mTc-NT-XIX in cultured HT-29 cancer cells at 37°C. HT-29 cells exhibited rapid internalization with 5.5% of radioactivity accumulated at 120 min after incubation. Approximately 50% of the internalized radioactivity remained inside the cells after 24 h of incubation. In vitro receptor-binding assays showed that the binding of 99mTc-NT-XIX to the HT-29 cells was saturable with a binding constant (Kd) value of 15 ± 6 nM (6). The Kd value for 125I-labeled NT was 1.6 nM.

Animal Studies

Rodents

[PubMed]

Garcia-Garayoa et al. (5) performed ex vivo biodistribution studies of 4 MBq (0.11 mCi) 99mTc-NT-XIX in nude mice (n = 3/group) bearing HT-29 xenografts. Tumor accumulation was 5.9 ± 1.1% injected dose (ID)/g at 1.5 h, 5.2 ± 0.5% ID/g at 5 h, and 2.5 ± 0.2% at 24 h after injection. The organ with the highest uptake was the intestines (5.2 ± 0.5% ID/g), followed by the kidneys (~4.8% ID/g), liver (~3.0% ID/g), and stomach (~1.5% ID/g); little radioactivity (<1% ID/g) accumulated in the muscle, pancreas, blood, and bone at 1.5 h after injection. The half-life of 99mTc-NT-XIX in blood from the injected mice was 1.4 h. Tumor/blood ratio was 13, 28, and 118 at 1.5, 5, and 24 h after injection, respectively. Co-administration of excess NT-XIX (0.3 mg/mouse) inhibited tumor accumulation by 78% at 1.5 h after injection, whereas accumulation in the intestines and stomach (NTR1-positive) was inhibited by 78% and 61%, respectively. Little effect was observed in the NTR1-negative tissues (kidneys, liver, pancreas, and muscle). SPECT imaging in nude mice bearing HT-29 xenografts was performed with 4 MBq (0.11 mCi) 99mTc-NT-XIX. The tumors were clearly visualized at 1.5 h after injection. Co-administration of excess NT-XI substantially inhibited the radioactivity in the tumors.

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.

References

1.
Vincent J.P., Mazella J., Kitabgi P. Neurotensin and neurotensin receptors. Trends Pharmacol Sci. 1999;20(7):302–9. [PubMed: 10390649]
2.
Carraway R.E., Plona A.M. Involvement of neurotensin in cancer growth: evidence, mechanisms and development of diagnostic tools. Peptides. 2006;27(10):2445–60. [PubMed: 16887236]
3.
Evers B.M. Neurotensin and growth of normal and neoplastic tissues. Peptides. 2006;27(10):2424–33. [PubMed: 16904238]
4.
Kitabgi P., De Nadai F., Rovere C., Bidard J.N. Biosynthesis, maturation, release, and degradation of neurotensin and neuromedin N. Ann N Y Acad Sci. 1992;668:30–42. [PubMed: 1463273]
5.
Garcia-Garayoa E., Blauenstein P., Blanc A., Maes V., Tourwe D., Schubiger P.A. A stable neurotensin-based radiopharmaceutical for targeted imaging and therapy of neurotensin receptor-positive tumours. Eur J Nucl Med Mol Imaging. 2009;36(1):37–47. [PubMed: 18690434]
6.
Maes V., Garcia-Garayoa E., Blauenstein P., Tourwe D. Novel 99mTc-labeled neurotensin analogues with optimized biodistribution properties. J Med Chem. 2006;49(5):1833–6. [PubMed: 16509599]

Views

  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this page (313K)
  • MICAD Summary (CSV file)

Search MICAD

Limit my Search:


Related information

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...