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Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors

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Nuclear Medicine Therapy

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Abstract

Somatostatin receptor targeting for imaging and treatment of neuroendocrine tumors with radiolabeled peptides has become an important topic over the last two decades. The somatostatin receptor, which is overexpressed in virtually all neuroendocrine tumors, belongs to the large family of G-protein coupled receptors (GPCRs).

Imaging of these tumors with radiopeptides is used for diagnosis, staging, restaging, and follow-up. Beside this, imaging is an important cornerstone to give the indication for treatment with radiopeptides. The registered radiopeptide 111In-pentetreotide is well established. However, a number of very efficient SPECT tracers labeled with 99mTc and PET agents based on the generator-produced 68Ga were developed and are nowadays employed regularly in the clinic.

For therapy somatostatin analogues labeled with the β-emitters 90Y and 177Lu are widely used. The most widely used compounds are 177Lu-DOTATATE ([177Lu-DOTA0,Tyr3,Thr8]-octreotide or [177Lu-DOTA0,Tyr3]-octreotate) and 90Y-DOTATOC ([90Y-DOTA0,Tyr3]-octreotide). As the same chelators and therefore the same conjugates can be used in diagnosis and therapy, these compounds constitute ideal theranostic pairs.

177Lu-DOTATATE was the first radiopeptide for therapy that received FDA-approval in January 2018. The approval was based on the recently published NETTER-1 study who compared 177Lu-DOTATATE therapy with high-dose long-acting octreotide in a randomized setting. The study showed that the median progression-free survival (PFS) was 8.5 months in the high-dose long-acting octreotide arm while it was not reached in the 177Lu-DOTATATE arm while side effects were tolerable. The most common grade 3–4 adverse reactions among patients receiving 177Lu-DOTATATE included lymphopenia, increased liver enzymes, nausea, hyperglycemia, and hypokalemia. With a median follow-up of 24 months, myelodysplastic syndrome was reported in 2.7% of patients receiving 177Lu-DOTATATE. Kidney toxicity—a major concern in radiopeptide therapy—was not observed. All patients received amino acid solution as a renal protectant.

Nowadays radiopeptide with radiolabeled somatostatin analogues is an established treatment for metastatic well-differentiated (G1 and G2) neuroendocrine tumors. The treatment is implemented in the widely accepted ENETS consensus guidelines of 2016.

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  1. Clinics of Radiology and Nuclear Medicine, Kantonsspital St. Gallen, St. Gallen, Switzerland

    Flavio Forrer

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  1. Nuclear Medicine and PET/CT Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

    Luca Giovanella

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Forrer, F. (2019). Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. In: Giovanella, L. (eds) Nuclear Medicine Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-17494-1_4

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