The Function of Depreotide in Tumor Receptor Imaging

2018-08-18

Introduction 

Somatostatin (SST) is a peptide compound synthesized by neuroendocrine cells and other cells that can label tumor cells, but the half-life of SST in the body is extremely short (4 min), which hinders the clinical application of SST. Therefore, people are committed to the research of the synthesis of somatostatin analogues (SSTA). Depreotide is a newly developed SSTA which is formed by solid phase synthesis of a tetrapeptide and a cyclic hexapeptide chain. The amino acid sequence is cyclo-(N-Me) Phe-Tyr-(D-Trp)-Lys-Val-Hcy [CH2CO-(β-Dap)-Lys-Cys-Lys-NH2].

Pharmacologic Action

Depreotide is mediated through the somatostatin receptor (SSTR) on the cell membrane to achieve its biological effects. SSTR belongs to the G protein-coupled receptor and exists on the surface of some normal tissue cells and tumor cells, and the distribution density on the surface of tumor cells is much higher than that of normal tissues. Depreotide has a long-lasting interaction with receptors and can be labeled with radionuclides for SSTR imaging and treatment of tumors. Moreover, depreotide as a disulfide-free cyclic SSTA can avoid the possibility of reductive cleavage of disulfide bonds during the labeling process, and a cysteine-containing 3 peptide sequence in its structure is Tc+5. Coordination electrons are provided and thus easily labeled by 99Tcm. Therefore, 99Tcm-depreotide somatostatin receptor imaging technology can effectively label and visualize tumor cells.

Function

A large number of experimental studies have confirmed that depreotide has a high affinity for SSTR2, SSTR3, and SSTR5, and depreotide is higher in tumor uptake than octreotide. The imaging quality is better than octreotide, and is more suitable for tumor imaging of lung cancer, especially non-small cell lung cancer. Another scholar found that 99Tc m-depreotide can be used not only to identify benign and malignant SPN, but also to diagnose regional lymph node involvement, distal bone metastases from lung cancer, breast cancer, meningioma and thyroid cancer. Besides, there are also advantages in the early the diagnosis of other tumors.

Pharmacokinetics and Metabolism

In a 99Tc m-depreotide-labeled A549 assay, the peak of 99mTc-depreotide in A549 cells was 60min at 37°C, and the clearance of 99mTc-depreotide by A549 cells was rapid and without temperature dependence. The half-clearing time of A549 cells up to 99Tc m-depreotide reached a maximum of 48min, indicating that 99Tc m-depreotide has a good biodegradability and will not accumulate in cells and produce cytotoxicity. In addition, depreotide is mainly excreted by the kidneys with low liver absorption and safe metabolism degradation.

References:

1. Rajeswaran W G, Hocart S J, Murphy W A, et al. Highly potent and subtype selective ligands derived by N-methyl scan of a somatostatin antagonist[J]. J Med Chem,2001,44(8):1305-1311.

2. Cyr JE, Pearson DA, Nelson CA, et al. Isolation, characterization, and biological evaluation of syn and anti-diastereomers of [(99m) Tc] technetium depreotide: a somatostatin receptor binding tumor imaging agent[J]. J Med Chem, 2007, 50(18): 4295-4303.

3. Van D B, Van Belles, Dewinter F, et al. Early prediction of endocrine therapy effect in advanced breast cancer patients using 99Tc m-depreotide scintigraphy[J]. J Nucl Med, 2006, 47(11): 6-13.

4. Virgolini I, Leimer M, Handmaker H, et al. Somatostatin receptor subtype specificity and in vivo binding of a novel tumor tracer, 99mTc-P829 [J]. Cancer Res, 1998, 58 (9): 1850-1859.

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