177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Dose Response in Small Intestinal Neuroendocrine Tumors

Neuroendocrinology. 2020;110(7-8):662-670. doi: 10.1159/000504001. Epub 2019 Oct 10.

Abstract

Introduction: Peptide receptor radionuclide therapy (PRRT) has during the last few years been frequently used in patients with progressive, disseminating, well-differentiated neuroendocrine tumors (NETs).

Objective: To study whether the absorbed dose in small intestinal NET (SI-NET) metastases from PRRT with 177Lu-DOTATATE is related to tumor shrinkage.

Materials and methods: Dosimetry for 1 tumor was performed in each of 25 SI-NET patients based on sequential SPECT/CT 1, 4, and 7 days after 177Lu-DOTATATE infusion. The SPECT data were corrected for the partial volume effect based on previous phantom measurements, and the unit density sphere model from OLINDA was used for absorbed dose calculations. Morphological therapy response was assessed by CT/MRI regarding tumor diameter, tumor volume, total liver tumor volume, liver volume, and overall tumor response according to RECIST 1.1. Plasma chromogranin A and urinary 5-hydroxy-indole-acetic-acid were measured during PRRT and follow-up to assess biochemical response.

Results: At the time of best response with respect to tumor diameter and volume shrinkage, the median absorbed dose was 128.6 Gy (range 28.4-326.9) and 140 Gy (range 50.9-487.4), respectively. All metrics regarding tumor shrinkage and biochemical response were unrelated to the absorbed dose. A correlation was, however, found between the administered radioactivity and the tumor volume shrinkage (p = 0.01) and between the administered radioactivity and RECIST 1.1 response (p = 0.01).

Conclusions: It was not possible to demonstrate a tumor dose-response relationship in SI-NET metastases with the applied dosimetry method, contrary to what was previously shown for pancreatic NETs.

Keywords: 177Lu-DOTATATE; Neuroendocrine tumors; Peptide receptor radionuclide therapy; Small intestinal tumors; Tumor dosimetry.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Radiation
  • Female
  • Follow-Up Studies
  • Humans
  • In Vivo Dosimetry
  • Intestinal Neoplasms / diagnosis
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / pathology
  • Intestinal Neoplasms / radiotherapy*
  • Intestine, Small / diagnostic imaging
  • Intestine, Small / pathology
  • Intestine, Small / radiation effects
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver / radiation effects
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / radiotherapy
  • Liver Neoplasms / secondary
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / radiotherapy*
  • Octreotide / administration & dosage
  • Octreotide / analogs & derivatives*
  • Octreotide / pharmacokinetics
  • Organ Size / radiation effects
  • Organometallic Compounds / administration & dosage*
  • Organometallic Compounds / pharmacokinetics
  • Radiotherapy Dosage
  • Tomography, X-Ray Computed
  • Tumor Burden / radiation effects

Substances

  • Organometallic Compounds
  • lutetium Lu 177 dotatate
  • Octreotide