Advances in Development of Radiometal Labeled Amino Acid-Based Compounds for Cancer Imaging and Diagnostics

Abstract

Radiolabeled biomolecules targeted at tumor-specific enzymes, receptors, and transporters in cancer cells represent an intensively investigated and promising class of molecular tools for the cancer diagnosis and therapy. High specificity of such biomolecules is a prerequisite for the treatment with a lower burden to normal cells and for the effective and targeted imaging and diagnosis. Undoubtedly, early detection is a key factor in efficient dealing with many severe tumor types. This review provides an overview and critical evaluation of novel approaches in the designing of target-specific probes labeled with metal radionuclides for the diagnosis of most common death-causing cancers, published mainly within the last three years. Advances are discussed such traditional peptide radiolabeling approaches, and click and nanoparticle chemistry. The progress of radiolabeled peptide based ligands as potential radiopharmaceuticals is illustrated via novel structure and application studies, showing how the molecular modifications reflect their binding selectivity to significant onco-receptors, toxicity, and, by that, practical utilization. The most impressive outputs in categories of newly developed structures, as well as imaging and diagnosis approaches, and the most intensively studied oncological diseases in this context, are emphasized in order to show future perspectives of radiometal labeled amino acid-based compounds in nuclear medicine.

Optimizing the Performance of 68Ga Labeled FSHR Ligand in Prostate Cancer Model by Means of Aprotinin

“…Radiolabeled peptides are useful approaches for cancer diagnosis and therapy. [25,26]A close relationship between FSHR and cancers suggested that it is a potential target of the disease. Although FSH1 analogs labeled with PET nuclides can speci cally bind to FSHR, low tumor uptakes may decrease the diagnostic sensitivity.…”

“…Enzyme inhibitors were proofed to increase metabolic stability and prolong tumor localization of the peptides. [16]After coinjection with the protease neutral endopeptidase, the percentage of intact radiopeptide, 177 Lu-DOTA-GRP (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), in the mouse circulation was prolonged and the tumor uptakes were also increased nearly three times. [17] Serine protease is found in eukaryotes, prokaryotes, archaea, and viruses.…”

Highly Specific L-Type Amino Acid Transporter 1 Inhibition by JPH203 as a Potential Pan-Cancer Treatment

“…Given the strictly localized LAT1 expression on tumors, LAT1 expression on the cancer cell membrane, and the recent insights on the LAT1 inhibition process, JPH203 might also have the potential to be further elaborated as radiotheranostic agents. Since a radiotheranostic approach counts heavily on radionuclide irradiation strength, only a trace mass of JPH203 would be required as vehicles to deliver this radiation straight into tumors [62]. In such a strategy, hepatotoxicity potential would be irrelevant.…”

Synthesis and Inhibition Activity Study of Triazinyl-Substituted Amino(alkyl)-benzenesulfonamide Conjugates with Polar and Hydrophobic Amino Acids as Inhibitors of Human Carbonic Anhydrases I, II, IV, IX, and XII

“…hCA IX plays a substantial role in pH regulation, adhesion, proliferation, migration, and invasion of tumor cells and correlates with poor patient prognosis and onco-therapy resistance [ 3 , 4 ]. There are many other well-known tumor-specific receptors and markers such as somatostatin, bombesin, glucagon-like peptide 1, prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP) [ 5 ]. The structural modification and development of novel small-molecule- or monoclonal-antibody-based compounds, with affinity and selectivity towards tumor-specific receptors/markers, belong to the most prospective approaches in the diagnosis, imaging, and therapy of hypoxic tumors, and so for personalized care of oncological patients [ 5 ].…”

“…There are many other well-known tumor-specific receptors and markers such as somatostatin, bombesin, glucagon-like peptide 1, prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP) [ 5 ]. The structural modification and development of novel small-molecule- or monoclonal-antibody-based compounds, with affinity and selectivity towards tumor-specific receptors/markers, belong to the most prospective approaches in the diagnosis, imaging, and therapy of hypoxic tumors, and so for personalized care of oncological patients [ 5 ]. Thus, a mechanism of the catalytic activity of tumor-associated hCA isozymes in hypoxic tumors and its inhibition has been a promising target over a long period in many studies by Supuran [ 6 , 7 , 8 , 9 ], Pastorek and Pastorekova [ 10 , 11 , 12 , 13 ] working groups and in other very recently published papers [ 14 , 15 , 16 , 17 , 18 ].…”