Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″- tetraacetic acid]-d-Phe¹,Tyr³-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed ⁶⁸Ga-DOTATATE accumulation in large vessels in comparison to ¹⁸F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors. Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBR_mean of both tracers with risk factors including plaque burden was assessed. Results: The mean TBR of ⁶⁸Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of ¹⁸F-FDG (r = 0.64; p < 0.01). There was one significant correlation between ¹⁸F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal ⁶⁸Ga-DOTATATE uptake, 16 (43.2%) also had focal ¹⁸F-FDG uptake. Of 39 sites with the highest ¹⁸F-FDG uptake, only 11 (28.2%) had a colocalized ⁶⁸Ga-DOTATATE accumulation. Conclusions: In this series of cancer patients, we found a stronger association of increased ⁶⁸Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to ¹⁸F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of ⁶⁸Ga-DOTATATE and ¹⁸F-FDG does not colocalize in a significant number of lesions.

Imbalances in NAD⁺ homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD⁺ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD⁺ synthesis. ¹⁸F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD⁺ salvage pathways and improve age-related symptoms.