This guideline on molar activity (A_m) and specific activity (A_s) focusses on small molecules, peptides and macromolecules radiolabelled for diagnostic and therapeutic applications. In this guideline we describe the definition of A_m and A_s, and how these measurements must be standardised and harmonised. Selected examples highlighting the importance of A_m and A_s in imaging studies of saturable binding sites will be given, and the necessity of using appropriate materials and equipment will be discussed. Furthermore, common A_m pitfalls and remedies are described. Finally, some aspects of A_m in relation the emergence of a new generation of highly sensitive PET scanners will be discussed.

The development of very fast, clean, and selective methods for indirect labeling in PET tracer synthesis is an ongoing challenge. Here we present the development of an ultrafast photoclick method for the synthesis of short-lived ¹⁸F-PET tracers based on the photocycloaddition reaction of 9,10-phenanthrenequinones with electron-rich alkenes. The respective precursors are synthetically easily accessible and can be functionalized with various target groups. Using a flow photo-microreactor, the photoclick reaction can be performed in 60 s, and clinically relevant tracers for prostate cancer and bacterial infection imaging were prepared to demonstrate practicality of the method.

Focused ultrasound (FUS) is a minimally-invasive technology used for treatment of many diseases, including diseases related to the colon, uterus, prostate, and brain. Although it has been mainly used for ablative procedures, the ability of FUS to open the blood-brain barrier (BBB) presents a promising new application. However, the mechanism of BBB opening by FUS remains unclear. This review focuses on the use of FUS to open the BBB for enhancing drug delivery and investigating how Positron Emission Tomography (PET) provides insight into the underlying mechanism.

P-glycoprotein is a protective efflux transporter at the blood–brain barrier showing altered function in many neurological disorders. The purpose of this study was to validate [¹⁸F]MC225 as a radiotracer for measuring P-glycoprotein function with positron emission tomography. Three groups of Sprague-Dawley rats were used to assess tracer uptake at baseline (group 1), after inhibition of P-glycoprotein (group 2), and after inhibition of both P-glycoprotein and breast cancer resistance protein (Bcrp, group 3). A two-tissue compartment model with a metabolite-corrected plasma input function provided the best fit to the positron emission tomography data, but parameter estimates were more reliable in a one-tissue compartment model, which was selected as the preferred model. Regional distribution volumes ( V_T) in the control group ranged from 6 to 11, which is higher than for other radiotracers. [¹⁸F]MC225 showed transporter selectivity, since inhibition of P-glycoprotein caused a two to fourfold increase in the cerebral V_T values, but additional inhibition of Bcrp did not cause any further increase. Metabolic stability of [¹⁸F]MC225 was moderate (at 1 h post-injection 15% of plasma radioactivity and 76% of brain radioactivity represented intact parent). Thus, [¹⁸F]MC225 may be a useful radiotracer to measure especially increases of P-glycoprotein function at the blood–brain barrier.

The blood-brain barrier (BBB) contributes to brain homeostasis by protecting the brain from harmful compounds. P-glycoprotein (P-gp) is one of the major efflux transporters at the BBB. In the present study, we assessed whether (1) P-gp function in the brain is constant or fluctuates across the day and (2) if it is affected by sleep deprivation. Four groups of rats were PET scanned with a radiolabeled P-gp substrate [18F]MC225, each at a different moment of the 12-h light-dark cycle to study diurnal variations: early sleep phase (ZT3), late sleep phase (ZT9), early active phase (ZT15), and late active phase (ZT21). In two additional groups, controls were allowed to sleep normally while experimental animals were sleep-deprived for 10 h in a slowly rotating drum during the sleep phase. Kinetic modeling with a one-tissue compartment model fit resulted for all brain regions in 1.2-1.8-fold higher distribution volumes (V T ) at ZT15 than at other time points. V T -values at ZT3, ZT9, and ZT21 were not significantly different from each other. Regional tracer distribution volumes in controls and sleep-deprived animals were also not significantly different. Our results indicate that P-gp function in rats displays a daily rhythm with reduced function at the beginning of the active phase. This rhythm is not dependent on sleep since acute sleep deprivation had no effect. Knowing the diurnal variation of P-gp function could be important for the design of PET studies and for choosing the correct administration time for P-gp-dependent drugs.