Longitudinal Multi-tracer PET/CT for Monitoring the Progression of Diabetic Cardiac Autonomic Neuropathy: A Preclinical Study.

Authors

Jing Gu, Hui Wang, Yulin He

Published in

Academic radiology. Sep 07, 2026. Epub Sep 07, 2026.

Abstract

This study utilized micro-positron emission tomography/computed tomography (micro-PET/CT) to track the longitudinal and dynamic progression of cardiac autonomic nerve injury in diabetic rats. Our objective was to map the precise timeline of neural damage relative to disease stages, defining a sensitive imaging window for the early diagnosis of diabetic cardiac autonomic neuropathy (DCAN).
Following streptozotocin induction of type 2 diabetes, rats underwent biweekly micro-PET/CT imaging for up to 17 weeks. Sympathetic and parasympathetic innervations were thoroughly evaluated using [¹¹C]C-MDA and [¹¹C]C-donepezil ([¹¹C]C-DNP), respectively. [¹¹C]C-triphenylmethylphosphonium ([¹¹C]C-TPMP) provided a perfusion baseline to characterize neuro-perfusion mismatches. Quantitative tracer uptake was correlated with histopathological remodeling and the myocardial expression of neurotrophic factors (NGF, GAP-43, CNTF) quantified via quantitative real-time polymerase chain reaction (RT-qPCR).
Longitudinal PET/CT imaging unveiled a distinct chronological cascade of cardiac deterioration. Parasympathetic denervation ([¹¹C]C-DNP depletion) manifested first at week 6, followed by sympathetic denervation ([¹¹C]C-MDA deficit) at week 8. Conversely, myocardial perfusion deficits ([¹¹C]C-TPMP) remained absent until week 16, escalating to severe metabolic dysfunction by week 17. Histopathology confirmed progressive myocardial inflammation, while RT-qPCR indicated a late-stage, yet insufficient, compensatory upregulation of neurotrophic factors.
This multi-tracer longitudinal investigation establishes that parasympathetic denervation precedes sympathetic impairment during DCAN development, with both deficits predating microvascular and metabolic crises. These insights offer a critical, noninvasive diagnostic window for early DCAN detection and clinical monitoring.

PMID:
42705925
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.

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