A Clinical Guide to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in Neuroendocrine Tumor Patients

Abstract

Peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-[DOTA⁰,Tyr³]-octreotate (¹⁷⁷Lu-DOTATATE) has become an established second- or third-line treatment option for patients with somatostatin receptor (SSTR)-positive advanced well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). Clinical evidence of the efficacy of PRRT in tumor control has been proven and lower risks of disease progression or death are seen combined with an improved quality of life. When appropriate patient selection is performed, PRRT is accompanied by limited risks for renal and hematological toxicities. Treatment of NET patients with PRRT requires dedicated clinical expertise due to the biological characteristics of PRRT and specific characteristics of NET patients. This review provides an overview for clinicians dealing with NET on the history, molecular characteristics, efficacy, toxicity and relevant clinical specifics of PRRT.

Keywords: 177Lu-DOTATATE; guide; neuroendocrine tumors; peptide receptor radionuclide therapy.

Figure 1

Mechanism of action of PRRT with ¹⁷⁷Lu-DOTATATE. Intravenous administration of ¹⁷⁷Lu-DOTATATE leads to tumor cell binding via SSTR₂. After internalization of the radiopharmaceutical–SSTR₂ complex, local radiation by beta particles can lead to cell death through the induction of DNA damage (image created with BioRender.com, accessed on 1 September 2022).

Figure 2

Potential complicated clinical situations for PRRT. (A) ⁶⁸Ga-DOTATATE PET scan of extensive bone metastases of SI-NET. R-PRRT with reduced activity of 3.7 GBq ¹⁷⁷Lu-DOTATATE induced hematoxicity. (B) Hydronephrosis (1) due to obstruction by peritoneal tumor deposit of metastatic panNET (2), leading to accumulation of radioactivity in renal medulla. (C) ⁶⁸Ga-DOTATATE PET scan showing extensive liver metastases of panNET before treatment with 3.7 GBq ¹⁷⁷Lu-DOTATATE, which was well tolerated by the patient. (D) Bone metastasis of panNET with epidural extension at Th12 on MRI. Post-PRRT edema can lead to infringement of the spinal cord. (E) Patient with small bowel NET and metastatic mesenteric mass with desmoplastic reaction, resulting in venous congestion, bowel wall thickening and ascites. The patient suffered from intermittent abdominal pain with temporary aggravation of complaints during PRRT. (F) Contrast enhanced CT scan of peritoneal metastases of a multifocal NET of a patient who developed a paralytic ileus or ‘frozen abdomen’ after PRRT.