In contrast to external high energy photon or proton therapy, targeted radionuclide therapy (TRNT) is a systemic cancer treatment allowing targeted irradiation of a primary tumor and all its metastases, resulting in less collateral damage to normal tissues. The α-emitting radionuclide bismuth-213 (²¹³Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with ²¹³Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of ²²⁵Ac and its daughter ²¹³Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth and general considerations for designing a ²¹³Bi-radiopharmaceutical are provided. Finally, we provide an overview of preclinical and clinical studies involving ²¹³Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

¹⁸F-MK-6240 is a highly selective, subnanomolar-affinity Positron Emission Tomography (PET) tracer for imaging neurofibrillary tangles (NFTs). Plasma kinetics, brain uptake, and preliminary quantitative analysis of ¹⁸F-MK-6240 in healthy elderly subjects (HE), subjects with clinically probable Alzheimer disease (AD), and amnestic mild cognitive impairment (MCI) were characterized in a first-in-human study. Methods: Dynamic PET scans of up to 150 min were performed in 4 cognitively normal HE, 4 AD and 2 MCI subjects, after bolus injection of 152-169 MBq ¹⁸F-MK-6240 to evaluate tracer kinetics and distribution in brain. Regional standardized uptake value ratio (SUVR) and distribution volume ratio (DVR) were determined using the cerebellar cortex as a reference region. Total distribution volume (VT) was assessed by compartmental modeling using radiometabolite corrected input function in a subgroup of 6 subjects. Results: ¹⁸F-MK-6240 had rapid brain uptake with peak standardized uptake value of 3-5, followed by a uniformly quick washout from all brain regions in HE; slower clearance was observed in regions commonly associated with NFT deposition in AD. In AD, SUVR measured between 60-90 min postinjection was high (approximately 2-4) in regions associated with NFT deposition; whereas, in HE, SUVR was approximately 1 across all brain regions suggesting high tracer selectivity for binding NFTs in vivo. ¹⁸F-MK-6240 VT was approximately 2- to 3-fold higher in neocortical and medial temporal brain regions of AD compared with HE, and stabilized by 60 min in both groups. DVR estimated by Logan reference tissue model or compartmental modeling correlated well (R² >0.9) to SUVR_{60-90 min} for AD. Conclusion: ¹⁸F-MK-6240 exhibited favorable kinetics with high-binding levels to brain regions with a plausible pattern for NFT deposition in AD. In comparison, negligible tracer binding was observed in HE. This pilot study suggests simplified ratio methods such as SUVR can be employed to quantify NFT binding. These results support further clinical development of ¹⁸F-MK-6240 for potential application in longitudinal studies.

Early diagnosis of disease and follow-up of therapy is of vital importance for appropriate patient management since it allows rapid treatment, thereby reducing mortality and improving health and quality of life with lower expenditure for health care systems. New approaches include nanomedicine-based diagnosis combined with therapy. Nanoparticles (NPs), as contrast agents for in vivo diagnosis, have the advantage of combining several imaging agents that are visible using different modalities, thereby achieving high spatial resolution, high sensitivity, high specificity, morphological, and functional information. In this work, we present the development of aluminum hydroxide nanostructures embedded with polyacrylic acid (PAA) coated iron oxide superparamagnetic nanoparticles, Fe₃O₄@Al(OH)₃, synthesized by a two-step co-precipitation and forced hydrolysis method, their physicochemical characterization and first biomedical studies as dual magnetic resonance imaging (MRI)/positron emission tomography (PET) contrast agents for cell imaging. The so-prepared NPs are size-controlled, with diameters below 250 nm, completely and homogeneously coated with an Al(OH)₃ phase over the magnetite cores, superparamagnetic with high saturation magnetization value (Ms = 63 emu/g-Fe₃O₄), and porous at the surface with a chemical affinity for fluoride ion adsorption. The suitability as MRI and PET contrast agents was tested showing high transversal relaxivity (r₂) (83.6 mM⁻¹ s⁻¹) and rapid uptake of ¹⁸F-labeled fluoride ions as a PET tracer. The loading stability with ¹⁸F-fluoride was tested in longitudinal experiments using water, buffer, and cell culture media. Even though the stability of the ¹⁸F-label varied, it remained stable under all conditions. A first in vivo experiment indicates the suitability of Fe₃O₄@Al(OH)₃ nanoparticles as a dual contrast agent for sensitive short-term (PET) and high-resolution long-term imaging (MRI).

Chronic obstructive pulmonary disease (COPD) is a common disease in industrialised countries and responsible for a considerable morbidity and mortality. Cigarette smoking is the most important aetiological factor. The EUROSCOP trial aims at investigating the hypothesis that airway inflammation plays an important pathogenic role in the development of chronic obstructive airway disease in smokers. In cigarette smokers with poorly reversible airflow obstruction, the effect over 3 yrs of an inhaled glucocorticosteroid, budesonide 400 micrograms b.i.d., on the decline of lung function, measured as postbronchodilator forced expiratory volume in one second (FEV1), will be compared with that of placebo. The trial has been designed to detect a difference in yearly decline of at least 30 ml.year-1. The study is a parallel group, randomised, double-blind, multicentre study. Patients will be recruited from 47 centres in 12 countries in Europe. It will start with a run-in consisting of two 3 month periods. During the first 3 months, the patients will be offered a smoking cessation programme. All patients who have not stopped smoking during this period will enter the second half of the run-in where compliance with the dosage regimen will be tested. After these two periods, patients will be randomised to receive either inhaled budesonide, 400 micrograms b.i.d., or placebo for a period of 3 yrs.