Two experts and a newbie: [18F]PARPi vs [18F]FTT vs [18F]FPyPARP—a comparison of PARP imaging agents

Purpose Imaging of PARP expression has emerged as valuable strategy for prediction of tumor malignancy. While [18F]PARPi and [18F]FTT are already in clinical translation, both suffer from mainly hepatobiliary clearance hampering their use for detection of abdominal lesions, e.g., liver metastases. Our novel radiotracer [18F]FPyPARP aims to bridge this gap with a higher renal clearance and an easily translatable synthesis route for potential clinical application. Methods We developed a less lipophilic variant of [18F]PARPi by exchange of the fluorobenzoyl residue with a fluoronicotinoyl group and automated the radiosyntheses of the three radiotracers. We then conducted a comparative side-by-side study of [18F]PARPi, [18F]FPyPARP, and [18F]FTT in NOD.CB17-Prkdcscid/J mice bearing HCC1937 xenografts to assess xenograft uptake and pharmacokinetics focusing on excretion pathways. Results Together with decent uptake of all three radiotracers in the xenografts (tumor-to-blood ratios 3.41 ± 0.83, 3.99 ± 0.99, and 2.46 ± 0.35, respectively, for [18F]PARPi, [18F]FPyPARP, and [18F]FTT), a partial shift from hepatobiliary to renal clearance of [18F]FPyPARP was observed, whereas [18F]PARPi and [18F]FTT show almost exclusive hepatobiliary clearance. Conclusion These findings imply that [18F]FPyPARP is an alternative to [18F]PARPi and [18F]FTT for PET imaging of PARP enzymes.

The Anti-Viral and Anti-Inflammatory Properties of Edible Bird’s Nest in Influenza and Coronavirus Infections: From Pre-Clinical to Potential Clinical Application

Edible bird’s nest (BN) is a Chinese traditional medicine with innumerable health benefits, including anti-viral, anti-inflammatory, neuroprotective, and immunomodulatory effects. A small number of studies have reported the anti-viral effects of EBN against influenza infections using in vitro and in vivo models, highlighting the importance of sialic acid and thymol derivatives in their therapeutic effects. At present, studies have reported that EBN suppresses the replicated virus from exiting the host cells, reduces the viral replication, endosomal trafficking of the virus, intracellular viral autophagy process, secretion of pro-inflammatory cytokines, reorient the actin cytoskeleton of the infected cells, and increase the lysosomal degradation of viral materials. In other models of disease, EBN attenuates oxidative stress-induced cellular apoptosis, enhances proliferation and activation of B-cells and their antibody secretion. Given the sum of its therapeutic actions, EBN appears to be a candidate that is worth further exploring for its protective effects against diseases transmitted through air droplets. At present, anti-viral drugs are employed as the first-line defense against respiratory viral infections, unless vaccines are available for the specific pathogens. In patients with severe symptoms due to exacerbated cytokine secretion, anti-inflammatory agents are applied. Treatment efficacy varies across the patients, and in times of a pandemic like COVID-19, many of the drugs are still at the experimental stage. In this review, we present a comprehensive overview of anti-viral and anti-inflammatory effects of EBN, chemical constituents from various EBN preparation techniques, and drugs currently used to treat influenza and novel coronavirus infections. We also aim to review the pathogenesis of influenza A and coronavirus, and the potential of EBN in their clinical application. We also describe the current literature in human consumption of EBN, known allergenic or contaminant presence, and the focus of future direction on how these can be addressed to further improve EBN for potential clinical application.

Circulating MicroRNAs in Blood and Other Body Fluids as Biomarkers for Diagnosis, Prognosis, and Therapy Response in Lung Cancer

The identification of circulating microRNAs (miRNAs) in peripheral blood and other body fluids has led to considerable research interest in investigating their potential clinical application as non-invasive biomarkers of cancer, including lung cancer, the deadliest malignancy worldwide. Several studies have found that alterations in the levels of miRNAs in circulation are able to discriminate lung cancer patients from healthy individuals (diagnosis) and are associated with patient outcome (prognosis) and treatment response (prediction). Increasing evidence indicates that circulating miRNAs may function as mediators of cell-to-cell communication, affecting biological processes associated with tumor initiation and progression. This review is focused on the most recent studies that provide evidence of the potential value of circulating miRNAs in blood and other body fluids as non-invasive biomarkers of lung cancer in terms of diagnosis, prognosis, and response to treatment. The status of their potential clinical application in lung cancer is also discussed, and relevant clinical trials were sought and are described. Because of the relevance of their biological characteristics and potential value as biomarkers, this review provides an overview of the canonical biogenesis, release mechanisms, and biological role of miRNAs in lung cancer.