64Cu-DOTATATE Positron Emission Tomography (PET) of Borrelia Burgdorferi Infection: In Vivo Imaging of Macrophages in Experimental Model of Lyme Arthritis

Abstract

Macrophages play a key role in the inflammatory response in Lyme arthritis (LA) and could be a target for diagnosing and monitoring active Borrelia burgdorferi sensu lato (Bb) infection. Therefore, we evaluated the potential of macrophage imaging using 64Cu-DOTATATE PET/CT for detection of Bb activity in a murine model of LA. LA was established in C3H/HeNRj mice infected with Bb B31 strain ML23 pBBE22luc. Bioluminescence imaging was performed to detect migration of spirochetes and inflammatory phagocytes to the joints. Three weeks post-infection 64Cu-DOTATATE PET/CT imaging was performed at an early (3 h) and late (48 h) time point. Plasma levels of a systemic macrophage marker in plasma CD163 were measured. 64Cu-DOTATATE uptake in infected joints was increased at the early (p < 0.0001) and late time points (p = 0.0005) compared with uptake in non-infected controls. No significant difference in plasma levels of CD163 was measured. 64Cu-DOTATATE PET allows for in vivo detection and quantification of LA locally in the joints through non-invasive visualization of macrophages. In contrast, measurement of a systemic macrophage marker in plasma, CD163, did not allow to detect disease. We suggest that 64Cu-DOTATATE PET could become a valuable diagnostic tool for in situ detection of Bb infection-related inflammation.

Medical imaging of pulmonary disease in SARS-CoV-2-exposed non-human primates

“…The inflammation-specific peptide DOTATATE [paired with gallium-68 ( 68 Ga) or copper-64 ( 64 Cu)], a radiotracer with specificity for somatostatin receptor 2 (SSTR2), was developed to improve the diagnosis of neuroendocrine tumors [94]. However, because SSTR2 is expressed by several inflammatory cells, DOTATA TE is being investigated as a potential tracer for evaluation of several conditions, including cardiovascular [95] and infectious diseases [96], and appears to be particularly advantageous for imaging cardiac inflammation [92]. In one case report, DOTATATE was detected in an axillary lymph node after COVID-19 vaccination [97,98].…”

Biomimetic Glucan Particles with Aggregation-Induced Emission Characteristics for Noninvasive Monitoring of Transplant Immune Response

“…In recent years, based on the phagocytosis activity of macrophages, , targeting cell surface receptors (chemokine, − somatostatin, and mannose), and detection of enzyme activity in macrophage, , magnetic resonance imaging (MRI) and nuclear imaging have been developed for tracing macrophages in vivo . However, the limited sensitivity of MRI, the safety issues of radionuclide imaging, and the finite half-life of radioisotopes hinder their application for real-time tracking of macrophages in a longitudinal manner.…”