Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes

Diabetologia. 2023 Nov;66(11):2164-2169. doi: 10.1007/s00125-023-05990-9. Epub 2023 Aug 15.

Abstract

Aims/hypothesis: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (68Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18F-fluorodeoxyglucose (18F-FDG). This study set out to investigate whether 68Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes.

Methods: Individuals aged >50 years with type 2 diabetes underwent 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV).

Results: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68Ga-DOTATATE PET/CT scans. The maximum TBR was -31% (95% CI -50, -12) lower in the coronary arteries, and bone marrow and splenic 68Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of -15% (95% CI -27, -4) and -17% (95% CI -32, -2), respectively.

Conclusions/interpretation: 68Ga-DOTATATE uptake across the cardio-haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT05730634.

Keywords: Atherosclerosis; Inflammation; Macrophages; Molecular imaging; Statin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atorvastatin / therapeutic use
  • Bone Marrow
  • Coronary Vessels
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Fluorodeoxyglucose F18
  • Gallium Radioisotopes
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Inflammation
  • Male
  • Middle Aged
  • Positron Emission Tomography Computed Tomography
  • Positron-Emission Tomography / methods
  • Spleen / diagnostic imaging

Substances

  • copper dotatate CU-64
  • Atorvastatin
  • Gallium Radioisotopes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Fluorodeoxyglucose F18

Associated data

  • ClinicalTrials.gov/NCT05730634