Tumor targeting with ^99mTc radiolabeled peptides: Clinical application and recent development

Abstract

Targeting overexpressed receptors on the cancer cells with radiolabeled peptides has become very important in nuclear oncology in the recent years. Peptides are small and have easy preparation and easy radiolabeling protocol with no side-effect and toxicity. These properties made them a valuable tool for tumor targeting. Based on the successful imaging of neuroendocrine tumors with 111 In-octreotide, other receptor-targeting peptides such as bombesin (BBN), cholecystokinin/gastrin analogues, neurotensin analogues, glucagon-like peptide-1, and RGD peptides are currently under development or undergoing clinical trials. The most frequently used radionuclides for tumor imaging are 99m Tc and 111 In for single-photon emission computed tomography and 68 Ga and 18 F for positron emission tomography imaging. This review presents some of the 99m Tc-labeled peptides, with regard to their potential for radionuclide imaging of tumors in clinical and preclinical application. K E Y W O R D S 99m Tc, radiolabeled peptides, SPECT, tumor targeting 206 | REZAZADEH AnD SADEGHZADEH some of them are currently under development or undergoing clinical trials. [13] Some of the most important peptides and their overexpressed receptors on tumors are listed in Table 1. 99m Tc is used for medical imaging in 80% of cases all over the world due to its near ideal nuclear characteristics of 6-hr half-life and γ-ray emission energy of 142 keV. Therefore, 99m Tc-labeled peptides with specific and high receptor affinity are very useful for tumor targeting. [14] The focus of this article remains the main applications of 99m Tc radiolabeled peptides in cancer research and development, which have been used in clinic and most promising candidates for future clinical use.

Peptide Multimerization as Leads for Therapeutic Development

“…The deployment of a peptide attached to a radio-nuclide has been the focus of a great deal of research to image specific peptide receptors and targeted activity towards receptors overexpressed on tumors over the last two decades [172]. For example, Khoshbakht et al developed a 18 F-FDG-Aoe-LIKKP-Pyr-F peptide with higher affinity for apoptotic cells and further hypothesised its potential in the diagnosis and therapy monitoring of apoptosisrelated pathologies [173].…”

Study of the 99mTc‐labeling conditions of 6‐hydrazinonicotinamide‐conjugated peptides from a new perspective: Introduction to the term radio‐stoichiometry

“…Somatostatin receptors are overexpressed on a number of human neuroendocrine tumors (NET) including pancreatic and gastrointestinal, small cell lung cancers (SCLC), pheochromocytomas, paragangliomas, and medullar thyroid carcinomas (MTCs); therefore, targeting the somatostatin (SST) receptors with peptide radiopharmaceuticals becomes an integral part of nuclear oncology during the two last decades. [30][31][32] Somatostatin is a natural cyclic neuropeptide with either 14 or 28 amino acids containing a disulfide-linkage. Both natural SST-14 and SST-28 can be bound with high affinity to five different receptor subtypes (sstr 1 -sstr 5 ), but they have a short plasma half-life because of rapid enzymatic degradation by endogenous peptidases.…”

Exploitation of CD133 for the Targeted Imaging of Lethal Prostate Cancer

“…Recently, a 68 Ga-labeled gastrin-releasing peptide receptor (GRPR) antagonist demonstrated success at detecting prostate cancer in patients with biochemical recurrence by PET/ MRI (25,26). Given the overexpression of neuropeptides in neuroendocrine tumors, it is highly probable that such agents could be used to image AVPC with neuroendocrine-differentiation (27)(28)(29). Other imaging modalities such as MRI and CT have been useful in detecting metastatic disease, but tell nothing of the underlying biology of the cancer cell (30).…”