Radiolabeled Peptides for Cancer Imaging and Therapy: From Bench-to-Bedside

Radiolabeled peptides can deliver radiation selectively to tumors via targeting peptide receptors that are overexpressed on the surface of cancer cells. The radiation is used either for detection (imaging) or for destruction (therapy) of these tumors. The Division of Radiopharmaceutical Chemistry at the University Hospital Basel has conducted pioneering work on the development of peptide-based radiopharmaceuticals. Our research covers the entire spectrum of such developments, from bench-to-bedside, and it is illustrated in this article by selective cases.

Synthesis of Novel, Dual-Targeting 68Ga-NODAGA-LacN-E[c(RGDfK)]2 Glycopeptide as a PET Imaging Agent for Cancer Diagnosis

Radiolabeled peptides possessing an Arg-Gly-Asp (RGD) motif are widely used radiopharmaceuticals for PET imaging of tumor angiogenesis due to their high affinity and selectivity to αvβ3 integrin. This receptor is overexpressed in tumor and tumor endothelial cells in the case of numerous cancer cell lines, therefore, it is an excellent biomarker for cancer diagnosis. The galectin-3 protein is also highly expressed in tumor cells and N-acetyllactosamine is a well-established ligand of this receptor. We have developed a synthetic method to prepare a lactosamine-containing radiotracer, namely 68Ga-NODAGA-LacN-E[c(RGDfK)]2, for cancer diagnosis. First, a lactosamine derivative with azido-propyl aglycone was synthetized. Then, NODAGA-NHS was attached to the amino group of this lactosamine derivative. The obtained compound was conjugated to an E[c(RGDfK)]2 peptide with a strain-promoted click reaction. We have accomplished the radiolabeling of the synthetized NODAGA-LacN-E[c(RGDfK)]2 precursor with a positron-emitting 68Ga isotope (radiochemical yield of >95%). The purification of the labeled compound with solid-phase extraction resulted in a radiochemical purity of >99%. Subsequently, the octanol–water partition coefficient (log P) of the labeled complex was determined to be −2.58. In addition, the in vitro stability of 68Ga-NODAGA-LacN-E[c(RGDfK)]2 was investigated and it was found that it was stable under the examined conditions.

Rapid 18F-labeling via Pd-catalyzed S-arylation in aqueous medium

Rapid Pd-catalyzed S-arylation with easily accessible 2-[18F]fluoro-5-iodopyridine enables facile preparation of radiolabeled peptides and proteins.

Radiolabeled Peptide Probes for Liver Cancer Imaging

Liver cancer/Hepatocellular Carcinoma (HCC) is a leading cause of cancer death and represents an important cause of mortality worldwide. Several biomarkers are overexpressed in liver cancer, such as Glypican 3 (GPC3) and Epidermal Growth Factor Receptor (EGFR). These biomarkers play important roles in the progression of tumors and could serve as imaging and therapeutic targets for this disease. Peptides with adequate stability, receptor binding properties, and biokinetic behavior have been intensively studied for liver cancer imaging. A great variety of them have been radiolabeled with clinically relevant radionuclides for liver cancer diagnosis, and many are promising imaging and therapeutic candidates for clinical translation. Herein, we summarize the advancement of radiolabeled peptides for the targeted imaging of liver cancer.

Radiolabeled Peptides for Molecular Imaging of Apoptosis

Apoptosis is a regulated cell death induced by extrinsic and intrinsic stimulants. Tracking of apoptosis provides an opportunity for the assessment of cardiovascular and neurodegenerative diseases as well as monitoring of cancer therapy at early stages. There are some key mediators in apoptosis cascade, which could be considered as specific targets for delivering imaging or therapeutic agents. The targeted radioisotope-based imaging agents are able to sensitively detect the physiological signal pathways which make them suitable for apoptosis imaging at a single-cell level. Radiopeptides take advantage of both the high sensitivity of nuclear imaging modalities and favorable features of peptide scaffolds. The aim of this study is to review the characteristics of those radiopeptides targeting apoptosis with different mechanisms.

Radiolabeled Peptides for SPECT and PET Imaging in the Detection of Breast Cancer: Preclinical and Clinical Perspectives

Breast cancer is the most common cancer in women worldwide. Due to the heterogeneous nature of breast cancer, the optimal treatment and expected response for each patient may not necessarily be universal. Molecular imaging techniques could play an important role in the early detection and targeted therapy evaluation of breast cancer. This review focuses on the development of peptides labeled with SPECT and PET radionuclides for breast cancer imaging. We summarized the current status of radiolabeled peptides for different receptors in breast cancer. The characteristics of radionuclides and major techniques for peptide labeling are also briefly discussed.