So PRRT is a molecular technique in which a radioisotope which is labeled with a small body which actually targets a particular receptor which is known as the somatostatin receptors is used to treat a specific kind of tumor known as a Neuroendocrine Tumor.
Now Neuroendocrine Tumors are malignant tumors which can arise from any part of the body most commonly either they arise from the pancreas or any part of the small or large bowels or can arise from the lungs or in certain cases it can even arise from the adrenal glands in which case they are known as Pheochromocytomas or they may arise along the sympathetic chain and be called paragangliomas.
Now these tumors when they metastasized they become… they can cause a lot of problems in the patient initially things like flushing, weight loss, diarrhea, raised insulin levels leading to hypoglycemia or it depends on if they are… these Neuroendocrine Tumor cells they secrete certain hormones which cause these changes in the body so it depends on the kind of neuro transmitter or hormone which this particular Neuroendocrine Tumors secretes and the patient may have symptoms depending on the kind of Neuroendocrine Tumor which he has. Most patients will may present with just diarrhea, or increased acidity or sometimes ulcers in the abdomen may present with interstellar obstruction. Now these Neuroendocrine Tumors specially the well differentiated Neuroendocrine Tumors are often refectory to chemotherapy.
So, chemotherapy does not work for these tumors. And the method of choice or the treatment of choice for these kind of tumors is a targeted therapy called PRRT. Now, PRRT stands for Peptide Radioisotope Therapy which basically uses small peptides which target the somatostatin receptors which are over expressed on these tumor cells to both diagnosed as well as to treat these tumor cells. So, the small bodies which target these somatostatin receptors which are labeled with certain isotopes like Gallium 68.
They are injected into the patient and the scan is called a Gallium DOTANOC or a Gallium DOTATATE Scan. Now Dota is a Key letter, Gallium is the radioisotope and “TOC” or “NOC” or “TATE” these are just the names of the peptides which are used to labeled this particular kind of tumor. So, when this radio pharmaceutical which is got a radioactive tail and it has got a peptide which targets this particular kind of a receptor on the Neuroendocrine Tumor is injected intravenously it enters the blood stream and it seeks out all those receptors which are expressed on the tumor cells. And because this is a very very targeted process, this kind of therapy only images or only treats the Metastatic Neuroendocrine Tumor and does not damage the surrounding cells because surrounding cells do not expressed based somatostatin receptors, So when we use a radioisotope which is capable of only imaging it is we will get a Pet Scan known as a Gallium DOTANOC PET CT which tells us number one not just whether a tumor is a Neuroendocrine Tumor or not, it tells us what is the extent of disease, whether the disease has a metastasize or spread from the primary site into the other organs, like the most common organ being the liver. Sometimes patients may come with a lot of metastatic lesions which somebody has picked up on either in Ultrasound or a CT and we don’t know where they are coming from, where is the primary, So the Gallium DOTANOC Scan also tells us in cases of Neuroendocrine Tumor as to where is the primary tumor because the treatments with differ depending on the primary site of tumor so if it is a primary which is coming from the pancreas the treatment may be a slightly different as compared to say a tumor which is coming from the small bowel or from the lung. So, this is the imaging of neuroendocrine tumors and you use something called a Gallium 68 DOTATOC or Gallium 68 DOTANOC scan to image these Neuroendocrine Tumors.
Now once we have image them comes the next step as to how to treat them. So, the same somatostatin receptor will now be targeted by another radioisotope which this time is a radioisotope which has a capability to kill a cell.
So, these are typically called either Beta Emitting or Alpha Emitting Radioisotopes. So, the most common Beta Emitting Radioisotope which is used for treatment of Neuroendocrine Tumors is Lutetium 177. Lutetium 177 is a beta emitting isotope which is labeled with a small body which targets the somatostatin receptors which is expressed on these Neuroendocrine Tumor Cells. It is injected either intravenously or sometimes even intra arterially. Especially in patients who have got a lot of disease in their liver the isotope may be directly injected into the liver artery and they’re by actually delivering the targeted radioisotope directly into the tumor sites in the liver. Now these radioisotopes then get stuck to the tumor cells they are internalized and because they are beta emitting or because they are emitting ionizing radiation or radiation which kills, this manage to kill these Neuroendocrine Tumor Cells and over a period of time these cells undergo what is known as Program Cell Death or “Apoptosis” and “Autophagy” and the patient’s tumor burden reduces the patient’s survival increases and most importantly the patient becomes symptomatically much better. Now most Neuroendocrine Tumor patients may be asymptomatic except for having pain or a you know weight loss some of these kinds of symptoms. But there are about to 15 to 20 % of Neuroendocrine Patients who will have a lot of symptoms depending on the kind of hormone which these Neuroendocrine Tumor are secreting.
So, patient may have a lot of diarrheas, lot of palpations, flushing, hypoglycemia and PRRT not just manages to reduce the tumor of bourdon on the patient but also gives the patient a lot of relief from these symptoms. Now PRRT may also be done with something called as an Alpha Emitter and then it is called an Alpha PRRT. Now what is alpha? Alpha is just like you have radioisotopes which emit beta rays you have radio isotopes which emit alpha rays. Alpha rays are much more potent in killing cells as compared to the beta rays and that is why Alpha PRRT is consider to be much more effective than beta PRRT but where is the difference the difference is that alpha rays will not have a very high penetration of within the tumor cell and as a results tumors which are large in size may not be adequately affected by the Alpha Emitting Radioisotopes.
So, Alpha Emitting Radioisotopes are primarily use for small volume disease whereas the Beta Emitting Radio isotopes actually are more suitable for patients who have got a large tumors and who have got a large volume of disease.
The Alpha Emitting Radioisotopes are things like Actinium (Ac225) or Bismuth (Bi213) so these are the common Alpha Emitting Radioisotopes which are used in the treatment of Neuroendocrine Tumor and this technique is called alpha PRRT.