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Targeted Alpha Peptide-receptor-radioligand-therapy (PRRT) is a kind of molecular therapy (also known as radioisotope therapy) that is used to treat neuroendocrine tumors (NETs).

Alpha PRRT uses alpha-emitting radionuclides such as actinium (Ac225), bismuth (Bi213), or lead (Pb212) to mark particular peptides and monoclonal antibodies. 

The conjugated compounds selectively connect to certain receptors on the surface of cancer cells, allowing them to target cancer cells.

Mechanism of Targeted Alpha-PRRT Therapy?

In PRRT, a cell-targeting protein (or peptide), identical to the natural circulating hormone somatostatin, is mixed with a small amount of radioactive material, or radionuclide, to create a radiopeptide, a unique sort of radiopharmaceutical.

This radiopeptide travels and binds to neuroendocrine tumor cells after being injected into the patient’s bloodstream, giving a concentrated high dosage of radiation precisely to the cancer cells.

Targeted Alpha-PRRT Therapy

The mechanism by which this radiopeptide can target the tumor cell is the abundance (called an overexpression) of a specific type of surface receptor—a protein that extends from the cell’s surface—that binds to somatostatin

What Conditions Are Treated with PRRT?

PRRT is used to treat neuroendocrine tumors, such as gastro-entero-pancreatic NETs, which are specific tumors that originate from the stomach, intestine, or pancreas, and are also known as carcinoids and islet cell carcinomas of the pancreas, and are the current USFDA (United States Federal Drug Association)-approved indication.

How is  Alpha PRRT Better Than Convention PRRT?

Many of the constraints of conventional Lutetium  (Lu177) PRRT that might be alleviated with targeted alpha PRRT are mentioned below:

  1. The alpha particles cause damage such as double-stranded DNA breakage and base chemical modifications as they are more energetic than the B particles deployed in traditional PRRT.
  2. Unlike the damage caused by beta particles, the damage induced by alpha particles is more difficult for the cancer cell to heal, resulting in faster cell death.
  3. Targeted alpha therapy has the ability to overcome the radioresistance to beta particles therapy. Also, because the alpha emitters range in tissue is measured in millimeters, results in the surrounding normal tissue being unaffected.
  4. Targeted Alpha Therapy, widely known as the “magic bullet,” is an excellent alternative for treating patients with neuroendocrine tumors, particularly those who do not respond to Lu177 PRRT or have become resistant to standard PRRT.

Who are the Targeted Patients?

Peptide-receptor-radioligand-therapy (PRRT) is  a good option of treatment for patients like:

  1. Patients suffering from advanced (metastatic) and/or progressive neuroendocrine tumors positive on somatostatin (growth hormone inhibitor) receptor imaging are suitable for the treatment.
  2. Patients who are not physically suitable for surgery.
  3. A patient whose symptoms stop responding to other medical treatments.

How it is Given?

The most common protocol referred to performing the Alpha Targeting PRRT therapy includes the following steps:

  1. Targeted Alpha PRRT is given as an intramuscular injection, just like traditional PRRT. 
  2. The patient is admitted to a high-dose therapy facility in the hospital.
  3.  In the forearm, an intravenous cannula is inserted. 
  4. To protect the kidneys, a specific amino acid infusion is given before the Alpha PRRT infusion. 
  5. Some patients may develop nausea as a result of the amino acid infusion, an antibiotic injection is given. 
  6. The alpha PRRT medication is given over the course of 20 minutes.

This special type of nuclear medicine therapy is performed as a full-day outpatient procedure but, in rare circumstances, a patient may be required to stay overnight as a precaution.

Molecular imaging scans (e.g. post-treatment Lu-177 scans) are being used to see where the injected radiopeptide has progressed in the body during and after therapy.

Significance of Alpha PRRT Therapy

PRRT and other molecular therapies provide more individually focused cancer treatment because radiopeptides can be adjusted to the patient’s specific biologic traits as well as the tumor’s molecular properties.

The therapy is well-considered because radiopeptides are very selective in their capacity to precisely reach and target neuroendocrine tumor cells while limiting radiation exposure to healthy tissues.

PRRT is a highly effective therapy option for advanced, metastatic, or incurable progressive neuroendocrine tumors. Although PRRT is rarely curative, it has been demonstrated to alleviate symptoms, decrease tumor lesions, and halt disease progression.

Adverse Effects of therapy?

Alpha PRRT with a specific target is well tolerated. During the infusion and for a few days afterward, some patients suffer nausea. The nausea is usually minor and can be treated with over-the-counter anti-nausea medication. 

There have been rare cases of delayed minor renal function derangement, but no patients have gone into irreversible renal failure. There is also no evidence of hematological harm.

A lowering of blood cell counts, which is mild to moderate in the majority of instances, is one of the long-term side effects. 

There are very few long-term side effects, such as irreversible kidney damage or the emergence of secondary hematologic neoplasms (a condition known as a myelodysplastic syndrome). The majority of patients tolerate the treatment well.

Is PRRT a Chemotherapy?

As a result, as compared to chemotherapy, PRRT often has less adverse effects. PRRT is a highly successful therapy option for managing advanced, progressing neuroendocrine tumors. 

PRRT is not a cure, but it has been demonstrated to help reduce symptoms and halt the disease’s course.

Is Targeted Therapy Better than Chemotherapy?

Chemotherapy and targeted therapy are two cancer-fighting medicines. Chemotherapy is more damaging to healthy cells than targeted therapy. 

Both of these techniques are frequently used in conjunction with other therapies like radiation.

Difference Between Targeted Therapy and Chemotherapy

Although targeted therapy is technically a form of chemotherapy but it does not work in the same way. The following are some of the distinctions between chemotherapy and targeted therapy:

  1. Chemotherapy is cytotoxic to cells, which means it attacks healthy cells as well as malignant cells whereas targeted therapy only kills malignant cells.
  2. Chemotherapy kills cancer cells that have already formed but targeted therapy can prevent cancer cells from multiplying, which means it can prevent the production of new cells.

Conclusion

The therapy’s goal is to stabilize the disease while attempting to increase progression-free survival. Over the last two years, nuclear oncologists have seen about 75–80% of patients on alpha PRRT acquire medical stabilization, with the majority reporting a significant improvement in their quality of life. Most patients report relief from discomfort and diarrhea, as well as an improvement in their overall health.

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