**4. Utilizing of peptides as radio-theranostic agents**

This part of the chapter will introduce the chemistry behind the radiolabeling of peptide-based diagnostic and/or therapeutic pharmaceutical systems used for nuclear oncological imaging and present research related to drug discovery in various areas such as chemistry, bioengineering, nanoscience, and nuclear oncology [70]. Synthetic peptide-based drugs labeled by radiochemically different techniques are used in routine clinical applications for diagnosis and therapy of diseases. Peptides targeting the somatostatin receptor subtypes have been routinely applied for peptide receptor radionuclide therapy (PRRT) of neuroendocrine and prostate cancers. Tumor regression, lengthening survival, and increased quality of life were observed in the patients treated with 177Lu-/90Y-labeled peptide conjugates [71]. This section provides an overview of various targeting and labeling techniques for receptor-targeted imaging.

**11**

[177Lu-DOTA0

,Tyr3

carried out using [90Y-DOTA0

125I-JR11 and agonist 125I-Tyr3

*Synthesis and Applications of Synthetic Peptides DOI: http://dx.doi.org/10.5772/intechopen.85486*

PRRT with radiolabeled peptide pharmaceuticals is a suitable and promising next-generation therapy method for inoperable patients with metastatic tumor. Radiolabeled peptide ligands are effective vectors for both detection and treatment of tumor cells overexpressing receptors specifically binding these ligands. Such radiopharmaceuticals, called as "theranostics," can be administered for diagnosis besides treatment, depending on the type of radionuclide being bound to the peptide sequence. Especially somatostatin and prostate-specific membrane antigen (PSMA)-based peptide analogues have significantly influenced the staging and therapy of patients. Mentioned analogues are used in clinical routine as an integral

PRRT and radiolabeled somatostatin (SST) peptide analogues are highly effective treatment agents. Somatostatin is in the form of dominant but functionally less active 14 amino acids called SST-14 and SST-28 in the form of a larger and stronger 28 amino acids [73]. According to the structure-activity researches of SST-14, although the amino acid residues of Phe, Trp, Lys, and Thr which contain a β-turn are important for bioactivity, different amino acids may be replaced by the Phe and Thr amino acids for this bioactivity, whereas Trp and Lys residues are definitely required. Octreotide, lanreotide, vapreotide, and pasireotide, which are the 4SS analogue synthetic peptides, are currently used actively in routine clinical applications. The octreotide compound, which is the synthetic peptide compared to the natural SST, was found to be 19 times more effective in inhibition of growth hormone secretion [74]. The presence of the D-Phe at the N-terminal end and the L-Thr at the C-terminal end and the replacement of the L-Trp at position 8 with D-Trp ensure that the peptide is resistant to degradation [75]. The somatostatin receptor family contains five receptor subtypes, sst1–sst5. Most of the neuroendocrine tumors, especially subtype 2 (sst2), have a strong overexpression of sst.

The clinical use of radiolabeled sst-targeting analogue [111In-DTPA0


lymphomas, renal cell cancer, and small-cell lung cancer [76, 77].

*4.1.2 Radionuclide therapy using PSMA analogues*

survival improvement can be provided with [90Y-DOTA0

initiated the development of numerous somatostatin analogues. This analogue is used as a theranostic agent in positive metastatic tumors. Tumor regression and

clinical studies with these agents in patients who suffered from GEP-NETs ranged from 9 to 33% [70]. As a result of the administration of the radiolabeled antagonist

antagonist binds to the SSTR2 region at a rate of 3.8–21.8-fold higher [76]. This significantly increased binding not only provides a more accurate localization in tumor and metastasis but also enables therapeutic interventions with radiolabeled SSTR antagonists to be more effective. Despite the low SSTR2 concentrations, tumors other than GEP-NETs and lung NETs have been targeted with SSTR2 antagonists; tumors of these types are breast cancer, medullary thyroid cancer, non-Hodgkin

PSMA has become an interesting target for the diagnosis and therapy of peptide receptors for small molecule ligands [78]. Since PSMA is often overexpressed in prostate cancer (PCa) cases, many different PSMA ligands are aimed

]octreotate. Several phase-1 and phase-2 PRRT trials were

]octreotide

]octreotide and

,Tyr3

]octreotide. Tumor regression responses in the


**4.1 Radiolabeled peptide analogues**

part of the treatment [72].

*4.1.1 Radionuclide therapy using somatostatin analogues*
