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.

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).

Terbium features four clinically interesting radionuclides for application in nuclear medicine: terbium-149, terbium-152, terbium-155, and terbium-161. Their identical chemical properties enable the synthesis of radiopharmaceuticals with the same pharmacokinetic character, while their distinctive decay characteristics make them valuable for both imaging and therapeutic applications. In particular, terbium-152 and terbium-155 are useful candidates for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging, respectively; whereas terbium-149 and terbium-161 find application in α- and β^--/Auger electron therapy, respectively. This unique characteristic makes the terbium family ideal for the “matched-pair” principle of theranostics. In this review, the advantages and challenges of terbium-based radiopharmaceuticals are discussed, covering the entire chain from radionuclide production to bedside administration. It elaborates on the fundamental properties of terbium, the production routes of the four interesting radionuclides and gives an overview of the available bifunctional chelators. Finally, we discuss the preclinical and clinical studies as well as the prospects of this promising development in nuclear medicine.

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.

Background: Gallium-68 labeled synthetic somatostatin analogs for PET/CT imaging are the current gold standard for somatostatin receptor imaging in neuroendocrine tumor patients. Despite good imaging properties, their use in clinical practice is hampered by the low production levels of⁶⁸Ga eluted from a⁶⁸Ge/⁶⁸Ga generator. In contrast,¹⁸F-tracers can be produced in large quantities allowing centralized production and distribution to distant PET centers. [¹⁸F]AlF-NOTA-octreotide is a promising tracer that combines a straightforward Al¹⁸F-based production procedure with excellent in vivo pharmacokinetics and specific tumor uptake, demonstrated in SSTR2 positive tumor mice. However, advancing towards clinical studies with [¹⁸F]AlF-NOTA-octreotide requires the development of an efficient automated GMP production process and additional preclinical studies are necessary to further evaluate the in vivo properties of [¹⁸F]AlF-NOTA-octreotide. In this study, we present the automated GMP production of [¹⁸F]AlF-NOTA-octreotide on the Trasis AllinOne® radio-synthesizer platform and quality control of the drug product in accordance with GMP. Further, radiometabolite studies were performed and the pharmacokinetics and biodistribution of [¹⁸F]AlF-NOTA-octreotide were assessed in healthy rats using μPET/MR.Results: The production process of [¹⁸F]AlF-NOTA-octreotide has been validated by three validation production runs and the tracer was obtained with a final batch activity of 10.8 ± 1.3 GBq at end of synthesis with a radiochemical yield of 26.1 ± 3.6% (dc), high radiochemical purity and stability (96.3 ± 0.2% up to 6 h post synthesis) and an apparent molar activity of 160.5 ± 75.3 GBq/μmol. The total synthesis time was 40 ± 3 min. Further, the quality control was successfully implemented using validated analytical procedures. Finally, [¹⁸F]AlF-NOTA-octreotide showed high in vivo stability and favorable pharmacokinetics with high and specific accumulation in SSTR2-expressing organs in rats.Conclusion: This robust and automated production process provides high batch activity of [¹⁸F]AlF-NOTA-octreotide allowing centralized production and shipment of the compound to remote PET centers. Further, the production process and quality control developed for [¹⁸F]AlF-NOTA-octreotide is easily implementable in a clinical setting and the tracer is a potential clinical alternative for somatostatin directed⁶⁸Ga labeled peptides obviating the need for a⁶⁸Ge/⁶⁸Ga-generator. Finally, the favorable in vivo properties of [¹⁸F]AlF-NOTA-octreotide in rats, with high and specific accumulation in SSTR2 expressing organs, supports clinical translation.