Effect of probenecid on the whole-body disposition of 6-bromo-7-[C]methylpurine in humans assessed with long axial field-of-view PET/CT.

Purpose: Multidrug resistance-associated proteins (MRPs) have a widespread tissue distribution. They play an important role in drug disposition and drug-drug interactions (DDIs) and have been associated with various diseases. PET with 6-bromo-7-[C]methylpurine ([C]BMP) has been used to assess MRP1 function in the brain and lungs of mice.

Immunogenicity, safety, and reactogenicity of concomitant administration of the novavax vaccine against Omicron XBB.1.5 (NVX-CoV2601) and a 20-valent pneumococcal conjugate vaccine in adults aged ≥60 years: A randomised, double-blind, placebo-controlled, non-inferiority trial.

Objectives: There is conflicting evidence as to whether the combined administration of two vaccines can lead to poorer immunogenicity and reactogenicity. The co-administration of the Omicron-adapted COVID-19 vaccine from Novavax (NVX-CoV2601) and a 20-valent pneumococcal conjugate vaccine (PCV20) has not been previously investigated.

Methods: In this randomised, double-blind, placebo-controlled, non-inferiority trial, immunocompetent participants aged ≥60 years were randomised in a 1:1:1:1 ratio to four groups: NVX-CoV2601 plus PCV20 (combination group); NVX-CoV2601 plus placebo (NVX-only group); PCV20 plus placebo (PCV20-only group); or placebo plus placebo (placebo group).

[C]Metoclopramide PET can detect a seizure-induced up-regulation of cerebral P-glycoprotein in epilepsy patients.

Background: P-glycoprotein (P-gp) is an efflux transporter which is abundantly expressed at the blood-brain barrier (BBB) and which has been implicated in the pathophysiology of various brain diseases. The radiolabelled antiemetic drug [C]metoclopramide is a P-gp substrate for positron emission tomography (PET) imaging of P-gp function at the BBB. To assess whether [C]metoclopramide can detect increased P-gp function in the human brain, we employed drug-resistant temporal lobe epilepsy (TLE) as a model disease with a well characterised, regional P-gp up-regulation at the BBB.

St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.

St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs.

Advancing 6-bromo-7-[C]methylpurine to clinical use: improved regioselective radiosynthesis, non-clinical toxicity data and human dosimetry estimates.

Background: 6-Bromo-7-[C]methylpurine ([C]BMP) is a radiotracer for positron emission tomography (PET) to measure multidrug resistance-associated protein 1 (MRP1) transport activity in different tissues. Previously reported radiosyntheses of [C]BMP afforded a mixture of 7- and 9-[C]methyl regioisomers. To prepare for clinical use, we here report an improved regioselective radiosynthesis of [C]BMP, the results of a non-clinical toxicity study as well as human dosimetry estimates based on mouse PET data.