**4.1 Radiolabeled peptide analogues**

*Peptide Synthesis*

new generation of more effective adjuvants is being studied. It is aimed to overcome the disadvantages of the traditional adjuvants with the development of modern adjuvants and delivery systems. Alum (insoluble salts of aluminum), which is a classical adjuvant, is a weak immune stimulant; its mechanisms of action are not fully elucidated and have a possibility of side effects. Emulsion adjuvants such as incomplete Freund's adjuvant (IFA), complete Freund's adjuvant (CFA), and lipid A are used; however, it is important to develop safer adjuvants due to their toxicity [46, 49, 57, 58]. Protein and synthetic polymer carriers play an important role in new-generation vaccine systems. The immunogenicity of peptide vaccines based on conjugation to protein and polymeric carriers is enhanced. Bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH), human serum albumin (HSA), and ovalbumin (OVA) are the most preferred proteins in peptide-protein conjugates [51, 59, 60]. In recent years, peptide-polymer conjugations using synthetic polymeric carriers have gained importance. Polymers to be selected in peptide-polymer conjugates, should be biocompatible, be relatively easy to synthesize and be modifiable according to the recommended use. This situation is pointed out that such polymers

Nanoparticles are investigated for their potential use as vaccine delivery systems. The use of nanoparticles in peptide-based vaccines may be useful in elimination of limitations with small peptide antigens. It can play a critical role in increasing the size of the antigen molecule, protecting the peptides from enzymatic degradation, and the delivery of the peptides to the targeted cells. Inorganic NPs, lipid-based NPs, polymeric NPs, and carbohydrates are common classes of nanoparticles. Especially polymeric NPs are of great interest for vaccination due to their biocompatibility and predictable degradation. In addition to natural polymers such as chitosan, dextran, and albumin, synthetic polymers such as polyesters, polyanhydrides, and polyamides can be mentioned. Mostly studied poly(lactic-coglycolic acid) (PLGA) is a synthetic copolymer composed of lactide and glycolide and approved by the European Medicine Agency (EMA) and US Food and Drug Administration (FDA) [64]. This polymer, which is biodegradable and biocompatible, is suitable for vaccine and drug delivery systems in humans. In the usage of polymeric nanoparticles as delivery systems for peptide vaccines, the peptide may be covalently/non-covalently attached to the surface of the particles through functional groups, or the peptide may be loaded into the nanoparticles [65–69].

Peptide vaccines are considered to be critical in the production of effective, safe, inexpensive, and easy to produce vaccines by the abovementioned advantages and

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

are important carrier candidates for peptide vaccines [61–63].

the development of new adjuvants.

receptor-targeted imaging.

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

**10**

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 part of the treatment [72].
