Peptide Receptor Radionuclide Therapy (PRRT)

Peptide receptor radionuclide therapy (PRRT) is a radionuclide therapy, which is based on specific binding of therapeutic radiopharmaceutical to somatostatin receptor (mostly sstr2) and internalization of receptor-radiopharmaceutical complex to exert radiation damage to neuroendocrine tumor cells. Although all kinds of tumors that have overexpression of somatostatin receptors are theoretically candidates for PRRT, it provides more successful results for gastroenteropancreatic and bronchial neuroendocrine tumors followed by some neuroectodermal tumors such as paraganglioma and some other tumors like thyroid medullary carcinoma or undifferentiated thyroid cancer with sstr2 overexpression. 177Lu-DOTATATE and 90Y-DOTATOC are currently the mostly preferred radiopharmaceuticals for PRRT. PRRT is administered mostly in 4–6 cycles of therapies, depending on the radiopharmaceutical used and on the clinical status of the patient. The repeated therapeutic cycles can be considered individually based on the patient. The dose-limiting organ for PRRT is the kidneys followed by the bone marrow. The patient should be assessed for an adequate renal function and bone marrow reserve in pretherapy setting. Renal toxicity can be reduced and avoided by kidney protecting amino acid solution infusions, which are administered just before PRRT. 90Y-DOTATOC usually causes more renal and bone marrow toxicity in comparison with 177Lu-DOTATATE. Therefore, 177Lu-DOTATATE should be the choice of radiopharmaceutical in case of compromised patients. PRRT with 90Y-DOTATOC and 177Lu-DOTATATE has been practised for more than a decade, and studies have so far concluded mostly partial and complete objective response rates in approximately 30% of patients without any serious side effects and severe toxicity when applied properly. The NETTER-1 trial has recently demonstrated prolonged survival in midgut neuroendocrine tumor patients who were treated with 4 cycles of 177Lu-DOTATATE PRRT, which gave rise to wide approval of PRRT. Alternatively, PRRT with alpha-emitting radiopharmaceuticals such as 125Ac-DOTATATE is also promising, especially for patients who do not respond well to PRRT with 177Lu-DOTATATE or 90Y-DOTATOC.