Peptide receptor radioligand therapy (PRRLT) is a type of molecular targeted radiation therapy used to treat certain types of cancer. It involves administering a peptide or protein linked to a radionuclide to selectively deliver radiation to cancer cells overexpressing specific receptors.
The components of PRRLT include:
- Peptide or protein ligands: Synthetic peptides or recombinant proteins that bind with high affinity and specificity to receptors overexpressed on cancer cells. Examples are somatostatin analogs and bombesin analogs.
- Radionuclide: A radioactive atom attached to the peptide/protein ligand, such as lutetium-177 and yttrium-90. It emits cytotoxic radiation to kill nearby cancer cells.
- Linker: A molecular linker used to join the peptide and radionuclide together without affecting receptor binding.
The mechanism of action involves:
- The radiolabeled peptide/protein binds to its cognate receptor that is overexpressed on the cancer cell surface.
- The radioligand-receptor complex becomes internalized into the cancer cell. This allows the radiation to be in close proximity to the DNA.
- The radionuclide then delivers a highly targeted dose of cytotoxic radiation to the cancerous cell without excessively affecting neighboring healthy cells.
~~PRRLT Process~~
Clinical applications of PRRLT
- Treatment of neuroendocrine tumors expressing somatostatin receptors, such as gastroenteropancreatic neuroendocrine tumors, using radiolabeled somatostatin analogs like ^177^Lu-DOTATATE.
- Treatment of metastatic castration-resistant prostate cancer using radiolabeled bombesin analogs like ^177^Lu-PSMA-617 which target prostate-specific membrane antigen (PSMA) receptors.
Advantages of PRRLT:
- Molecular targeted approach: By selectively targeting receptors on cancer cells, PRRLT spares healthy cells from radiation damage.
- High therapeutic index: Concentrates dose delivery specifically to cancerous cells.
- "Precision medicine": Treatment can be personalized based on a patient's receptor status.
- Minimally invasive: Administered intravenously with minimal side-effects compared to external beam radiation therapy.
- Outpatient procedure: Does not require prolonged hospitalization.
