NUCLEAR MEDICINE THERAPY
Peptide receptor radionuclide therapy (PRRT)
The abbreviation PRRT stands for "peptide receptor radionuclide therapy" (synonym: peptide receptor radio-therapy) and represents a treatment method for patients with neuroendocrine tumors.
Neuroendocrine tumors (NET) are benign or malignant tumors developing from the cells of the neuroendocrine system. These cells are scattered throughout the body and are characterized by the release of hormones that influence various organ systems in the body. The most frequently affected sites are pancreas, gastrointestinal tract, and the lungs, and often with metastases (extension of the tumor) to the liver, lymph nodes, and bones.
Targeted irradiation of the tumor cell "from within", sparing the healthy tissue. Neuroendocrine tumors and their metastases express special molecules on their surface. These are somatostatin receptors, serving as target structures for the synthetically produced peptides (DOTATATE or DOTATOC). These protein compounds (peptides) are coupled to therapeutically effective radionuclides (Lutetium-177 or Yttrium-90), so that tumor cells can be selectively targeted and destroyed from within, from the radiation. As the range of radiation emitted is only up to a few millimeters, healthy tissue is largely spared.
PRRT is usually performed using the beta emitters Lutetium-177 (Lu-177) and Yttrium-90 (Y-90). The alpha emitter Actinium-225 (Ac-225) has a much higher energy compared to Lu-177 or Y-90, and a very short range, which results in a higher rate of double-strand-DNA-breaks in tumor cells. Ac-225 DOTATOC is a novel therapy option, which can be used after failure of a PRRT using Lu-177 or Y-90, or in selected cases, with extensive metastases.
The indication for PRRT is confirmed in the interdisciplinary tumor board along the guidelines of ENETS (European Neuroendocrine Tumor Society), and comprises of medical specialists from different disciplines (general and visceral surgery, internal medicine and gastroenterology, oncology, nuclear medicine, and radiology). The current tumor status, previous treatments (surgery, chemotherapy, radiation therapy, etc.) and imaging (PET/CT, CT, MRI, etc.) are taken into account. Decisions on therapy planning are taken by consensus, and appropriate recommendations are made accordingly. A pre-therapy Gallium-68 DOTATOC PET/CT is necessary in order to determine somatostatin receptor expression of the primary tumor and/or metastases, and thus, to assess the feasibility of PRRT. In addition, function of the kidneys is examined in advance by means of a renal scintigraphy. Relevant laboratory values (e.g. parameters of liver and renal function, complete blood count, electrolytes and tumor markers) are also reviewed.
Due to radiation protection regulations in Germany, PRRT requires an inpatient stay of at least 48 hours following the radiopharmaceutical injection on our therapy ward. In general, but catering to the individual patient, three to four therapy cycles are performed at intervals of around three months. On the day of treatment, before and after the infusion of the radiopharmaceutical, an amino acid solution is administered via a vein to protect the kidneys. The radioisotope is finally administered over 20 minutes via the same intravenous access, under direct medical supervision, and regular monitoring of blood pressure and pulse rate. In order to assess the uptake and bio-distribution of injected radiopharmaceutical in the patient's body, a so-called whole-body scintigraphy and/or a three-dimensional SPECT/CT is performed on the days following PRRT. This information is important for further therapy planning and for predicting therapy response, and possible side effects.
In general, PRRT is a well-tolerated therapy. Nevertheless, side effects can occur as with any other therapy or drug.
The most common, usually mild and reversible (short-term), adverse effects observed after and/or under PRRT are:
- Abdominal discomfort
- Possibility of a carcinoid reaction, that is exacerbation of pre-existing symptoms in patients with a functionally highly active neuroendocrine tumor
However, these symptoms can be treated with medications. To avoid occurrence of such adverse effects, adequate premedication is administered.
Other possible side effects on a longer term are:
- Bone marrow suppression (usually temporary)
- Kidney dysfunction (rare)
- Temporary hair loss (temporary)
- Liver dysfunction (very rare)
Following PRRT, regular clinical and imaging follow up (restaging) is essential. The frequency and duration of restaging is personalized and planned interdisciplinary, as well as in cooperation with the treating physician of the patient. The restaging at our Clinic for Nuclear Medicine includes a concise clinical review including questions regarding current symptoms of the disease (e.g., flushing, diarrhea, shortness of breath, pain, etc.), as well as the assessment of laboratory values (blood count, liver and kidney function tests, tumor markers, etc.), and the monitoring of renal function by means of scintigraphy according to standard PRRT guidelines, and other imaging procedures, as deemed necessary. As a rule, this follow-up examination takes place on an outpatient basis. With regard to imaging, PET/CT as well as CT, MRI, and if necessary, ultrasound examinations are performed according to the guidelines. If several examinations are necessary, but cannot be completed in one day, it is possible to stay overnight in the hospital-provided guest rooms. Finally, the interdisciplinary tumor board discusses the further course of clinical management following review of the restaging findings and makes the appropriate recommendation for the patient.
Registration form PRRT: Download (pdf)