Glucagon-Like Peptide-1 Receptor-Targeted PET/CT With 68 Ga-HBED-CC-Exendin-4 in Localizing Insulinoma : A Head-to-Head Comparison to 68 Ga-NOTA-Exendin-4

Clin Nucl Med. 2025 Jan 1;50(1):38-43. doi: 10.1097/RLU.0000000000005533. Epub 2024 Nov 8.

Abstract

Purpose: Modifying glucagon-like peptide-1 receptor (GLP-1R)-targeted PET agent to achieve faster renal clearance and preserved high affinity to GLP-1R is clinically relevant. The aim of this study is to assess the performance of a newly developed GLP-1R-targeted agent, 68 Ga-HBED-CC-exendin-4 in localizing insulinoma, and its biodistribution, as compared with previously introduced 68 Ga-NOTA-exendin-4.

Patients and methods: Nineteen patients with endogenous hyperinsulinemic hypoglycemia were enrolled and referred for 68 Ga-HBED-CC-exendin-4 PET/CT and 68 Ga-NOTA-exendin-4 PET/CT within 2 consecutive days. Diagnostic performance of the 2 tracers in localizing insulinoma was evaluated, and SUV of the lesion, normal pancreas background, kidneys, and bladder were measured.

Results: 68 Ga-HBED-CC-exendin-4 and 68 Ga-NOTA-exendin-4 PET/CT exhibited an equivalent efficacy in detection rate (both sensitivity of 100%). Although SUV max of the tumor in 68 Ga-HBED-CC-exendin-4 was significantly lower than that in 68 Ga-NOTA-exendin-4 (20.01 ± 9.41 vs 31.78 ± 15.46, P < 0.001) at 50 minutes postinjection, there was no significant difference in the tumor-to-background ratio between the 2 agents (8.61 ± 3.57 vs 8.18 ± 3.38, P = 0.326), and the lesions could be visible as early as 4 minutes postinjection for both agents in patients who underwent dynamic PET/CT. In addition, 68 Ga-HBED-CC-exendin-4 exhibited approximately 30% decrease of the renal accumulation compared with 68 Ga-NOTA-exendin-4 (SUV mean , 42.21 ± 5.79 vs 58.58 ± 10.06 at 50 minutes, P < 0.001).

Conclusions: 68 Ga-HBED-CC-exendin-4 is an effective agent for localizing insulinoma showing similar detectability and tumor-to-background ratio compared with 68 Ga-NOTA-exendin-4. Notably, 68 Ga-HBED-CC-exendin-4 exhibits significantly lower renal uptake than 68 Ga-NOTA-exendin-4, which might potentially benefit the detection of the tumors adjacent to the left kidneys.

Trial registration: ClinicalTrials.gov NCT05034783.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Exenatide* / pharmacokinetics
  • Female
  • Gallium Radioisotopes*
  • Glucagon-Like Peptide-1 Receptor*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring* / chemistry
  • Heterocyclic Compounds, 1-Ring* / pharmacokinetics
  • Humans
  • Insulinoma* / diagnostic imaging
  • Insulinoma* / metabolism
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / diagnostic imaging
  • Peptides / chemistry
  • Peptides / pharmacokinetics
  • Positron Emission Tomography Computed Tomography*
  • Tissue Distribution
  • Venoms / pharmacokinetics
  • Vinyl Compounds

Substances

  • Exenatide
  • Glucagon-Like Peptide-1 Receptor
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid
  • Heterocyclic Compounds
  • Venoms
  • Peptides
  • 1,4,7-tris(carboxymethyl)-10-(vinylsulfone)-1,4,7,10-tetraazacyclododecane
  • Vinyl Compounds

Associated data

  • ClinicalTrials.gov/NCT05034783