The peptide is one kind of delivery molecule for RDC (Radionuclide Drug Conjugate), which can drive the RDC compound to the targeting diseased tissue. The most commonly used peptide in RDC is the one that can identify the SSTR (Somatostatin Receptor).
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RDC has received a lot of attention because of the many difficulties in treating cancer with conventional chemotherapy and radiotherapy, such as cancer becoming resistant and patients becoming sicker. The peptide is one type of RDC delivery vehicles. The peptide in RDC mainly refers to the one targeting the SSTR, a special overexpressed marker on the membrane of neuroendocrine tumors, which is named growth inhibitor analogs. Neuroendocrine tumors are relatively slow growing and less malignant than other cancers and are most commonly found in the gastrointestinal tract and pancreas. RDC preferentially gathers at the neuroendocrine tumors because of the peptide-receptor binding.
Fig.1 Illustration of peptide-based RDC.
This novel therapy is termed PRRT (Peptide Receptor Radionuclide Therapy). After the targeted binding, the growth inhibitor analogs and radionuclides are transported into tumor cells, where they exert a dual effect of biotherapy and intra-tumor irradiation to kill the tumor cells. As RDC, the radiopharmaceutical for PRRT is constructed with three components, including the radionuclide, chelator-linker, and somatostatin analogue, the targeting part. The radionuclide part delivers the actual therapeutic effect by the radioactive beam in the RDC. The chelator-linker part is the essential band between the radionuclide and peptide.
The most commonly used radiopharmaceutical in PRRT is DOTATOC or DOTATATE chemically bound to a gamma-emitting radioactive material, including indium-111, lutetium-177, and yttrium-90, in which indium-111 was primarily used for imaging alone and is now used for radiotherapy in high doses. Binding with a gamma-emitting particle in the radionuclide part, the radiopharmaceutical can be used for diagnostic imaging with SPECT or PET scanner to locate tumors at the cell level. When chelated with alpha or beta emitting particles, radiopharmaceuticals can gather at diseased tissue and damage the tumor cells. 177Lu-DOTATATE has been approved since 2018 for the gastroenteropancreatic neuroendocrine tumors.
Fig.2 Diagram of peptide synthesis.
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