Ion beam induced 18F-radiofluorination: straightforward synthesis of gaseous radiotracers for the assessment of regional lung ventilation using positron emission tomography.

A simple, straightforward and efficient method for the synthesis of [18F]CF4 and [18F]SF6 based on an ion beam-induced isotopic exchange reaction is presented. Positron emission tomography ventilation studies in rodents using [18F]CF4 showed a uniform distribution of the radiofluorinated gas within the lungs and rapid elimination after discontinuation of the administration.

Straightforward synthesis of radioiodinated Cc-substituted o-carboranes: towards a versatile platform to enable the in vivo assessment of BNCT drug candidates.

Due to their high boron content and rich chemistry, dicarba-closo-dodecaboranes (carboranes) are promising building blocks for the development of drug candidates with application in Boron Neutron Capture Therapy. However, the non-invasive determination of their pharmacokinetic properties to predict therapeutic efficacy is still a challenge. Herein, we have reported the unprecedented preparation of mono-[(125)I] iodinated decaborane via a catalyst-assisted isotopic exchange. Subsequent reactions of the radiolabelled species with acetylenes in acetonitrile under microwave heating yield the corresponding (125)I-labelled, Cc-substituted o-carboranes with good overall radiochemical yields in short reaction times. The same synthetic strategy was successfully applied to the preparation of (131)I-labelled analogues, and further extension to other radioisotopes of iodine such as (124)I (positron emitter) or (123)I (gamma emitter) can be envisaged. Hence, the general strategy reported here is suitable for the preparation of a wide range of radiolabelled Cc-substituted o-carborane derivatives. The labelled compounds might be subsequently investigated in vivo by using nuclear imaging techniques such as Single Photon Emission Computerized Tomography or Positron Emission Tomography.

Visualisation of dual radiolabelled poly(lactide-co-glycolide) nanoparticle degradation in vivo using energy-discriminant SPECT.

The determination of nanoparticle (NP) stability and degradation in vivo is essential for the accurate evaluation of NP biodistribution in medical applications and for understanding their toxicological effects. Such determination is particularly challenging because NPs are extremely difficult to detect and quantify once distributed in a biological system. Radiolabelling with positron or gamma emitters and subsequent imaging studies using positron emission tomography (PET) or single-photon emission computerised tomography (SPECT) are some of the few valid alternatives. However, NPs that degrade or radionuclides that detach or are released from the NPs can cause artefact. Here, submicron-sized poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) stabilised with bovine serum albumin (BSA) were dual radiolabelled using gamma emitters with different energy spectra incorporated into the core and coating. To label the core, 111In-doped iron oxide NPs were encapsulated inside PLGA-NPs during NP preparation, and the BSA coating was labelled by electrophilic substitution using 125I. After intravenous administration into rats, energy-discriminant SPECT resolved each radioisotope independently. Imaging revealed different fates for the core and coating, with a fraction of the two radionuclides co-localising in the liver and lungs for long periods of time after administration, suggesting that NPs are stable in these organs. Organ harvesting followed by gamma counting corroborated the SPECT results. The general methodology reported here represents an excellent alternative for visualising the degradation process of multi-labelled NPs in vivo and can be extended to a wide range of engineered NPs.

Long-term therapy with recombinant interferon-gamma (rIFN-gamma) for atopic dermatitis.

BACKGROUND: Interferon-gamma (IFN-gamma) is a potent cytokine that modulates IL-4-induced immune responses. Atopic dermatitis is associated with increased IgE levels and decreased IFN-gamma production. Recent phase I and phase II studies have suggested that short-term rIFN-gamma therapy is effective in the treatment of severe atopic dermatitis. OBJECTIVE: We evaluated the safety and efficacy of long-term use of rIFN-gamma for severe atopic dermatitis. METHODS: Fifteen patients were treated for a minimum of 22 months with 50 micrograms/m2 rIFN-gamma qd or qod. Patients were monitored every 3 months for safety, efficacy, and linear growth in pediatric patients. RESULTS: Data represented a total of 47 patient years, which included 29 pediatric patient years. There was a statistically significant decrease in mean total body surface area involvement over time (P < .001, ANOVA). Mean total body surface area involvement was 61.6% at baseline and decreased to 18.5% at 24 months (P < .001). Likewise, there was a statistically significant decrease in the clinical severity parameters. The mean total clinical severity score was 11.4 at baseline and decreased to 6.3 at 24 months (P < .001). Statistically significant decreases in WBC, neutrophil counts, and eosinophil counts were observed compared with baseline counts. No other significant laboratory abnormalities or growth problems were seen. CONCLUSIONS: We conclude that rIFN-gamma appears to be a safe long-term therapy for patients with severe atopic dermatitis.