Neurological Complications of Biological Treatment of Psoriasis

In the available literature, little attention has been paid to the assessment of psoriasis and the biological therapy used for it and the nervous system. The purpose of this article is to discuss the relationship between psoriasis and the nervous system as well as to analyze the mechanisms that lead to neurological complications during anticytokine therapies in psoriasis. However, this connection requires further analysis. The use of biological drugs in psoriasis, although it yields positive therapeutic results, is not without numerous side effects. Serious neurological side effects of the therapy are most often visible with the use of anti-TNF-alpha, which is why patients should be monitored for their potential occurrence. Early detection of complications and rapid discontinuation of treatment with the drug may potentially increase the patient’s chances of a full recovery or improvement of his/her neurological condition. It also seems reasonable that, in the case of complications occurring during anti-TNF-alpha therapy, some of the drugs from other groups should be included in the therapy.

212Pb: Production Approaches and Targeted Therapy Applications

Over the last decade, targeted alpha therapy has demonstrated its high effectiveness in treating various oncological diseases. Lead-212, with a convenient half-life of 10.64 h, and daughter alpha-emitter short-lived 212Bi (T1/2 = 1 h), provides the possibility for the synthesis and purification of complex radiopharmaceuticals with minimum loss of radioactivity during preparation. As a benefit for clinical implementation, it can be milked from a radionuclide generator in different ways. The main approaches applied for these purposes are considered and described in this review, including chromatographic, solution, and other techniques to isolate 212Pb from its parent radionuclide. Furthermore, molecules used for lead’s binding and radiochemical features of preparation and stability of compounds labeled with 212Pb are discussed. The results of preclinical studies with an estimation of therapeutic and tolerant doses as well as recently initiated clinical trials of targeted radiopharmaceuticals are presented.

Feasibility of a novel photoproduction of 225Ac and 227Th with natural thorium target

We propose an innovative way to produce both 225Ac and 227Th, two precious radioisotopes enabling promising targeted alpha therapy, in a natural thorium target bombarded with a 30–90 MeV electron beam. Bremsstrahlung photons in the target are analyzed by MCNP and in-situ photonuclear transmutation of 232Th is evaluated by using the TENDL nuclear data. In the photo-transmutation analysis, 13 nuclides including 229Th and 231Pa are modelled. Special procedures with chemical separations are also proposed to produce pure 225Ac and 227Th in separate streams. In addition, performance of the new approach is compared with conventional methods in terms of the 225Ac and 227Th yields. After a Th target is bombarded with a 500 kW electron beam for a year, yearly 225Ac yield is ~ 8.47 GBq (semi-permanently) and yearly 227Th yield is ~ 48.9 GBq over 50 years, and their yields are at least doubled in a 2-year irradiation. This work will help increase global supply of the two precious isotopes and would invariably help advance TAT-related researches and developments.

Performance improvement of Compton imaging of astatine-211 by optimising coincidence time windows

Astatine-211 is one of the promising radioisotopes for targeted alpha therapy. Optimising treatment strategies as well as determining the suitability of a given agent for a particular patient requires to image the time-dependent distribution of the targeted radiotherapeutic agent both in tumours and in normal tissues. Since the biodistribution of astatine is different from that of iodine, imaging astatine-211 directly is essential. In the previous study of astatine-211 Compton imaging, random coincidence events due to polonium K-shell X-rays were dominant and seemed to cause saturation of counts. Thus optimisation of the coincidence time windows is important to reduce random coincidence events. In this study, we have optimised the coincidence time windows of a Compton camera and improved the sensitivity, noise and spatial resolution of astatine-211 imaging.

A Novel Single-Step-Labeled 212Pb-CaCO3 Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice

Lead-212 is recognized as a promising radionuclide for targeted alpha therapy for tumors. Many studies of 212Pb-labeling of various biomolecules through bifunctional chelators have been conducted. Another approach to exploiting the cytotoxic effect is coupling the radionuclide to a microparticle acting as a carrier vehicle, which could be used for treating disseminated cancers in body cavities. Calcium carbonate may represent a suitable material, as it is biocompatible, biodegradable, and easy to synthesize. In this work, we explored 212Pb-labeling of various CaCO3 microparticles and developed a protocol that can be straightforwardly implemented by clinicians. Vaterite microparticles stabilized by pamidronate were effective as 212Pb carriers; labeling yields of ≥98% were achieved, and 212Pb was strongly retained by the particles in an in vitro stability assessment. Moreover, the amounts of 212Pb reaching the kidneys, liver, spleen, and skeleton of mice following intraperitoneal (i.p.) administration were very low compared to i.p. injection of unbound 212Pb2+, indicating that CaCO3-bound 212Pb exhibited stability when administered intraperitoneally. Therapeutic efficacy was observed in a model of i.p. ovarian cancer for all the tested doses, ranging from 63 to 430 kBq per mouse. Lead-212-labeled CaCO3 microparticles represent a promising candidate for treating intracavitary cancers.

Radiotheranostic Agents Targeting Neuroblastoma: State-of-the-Art and Emerging Perspectives

Neuroblastoma (NB) represents the most common extracranial tumor of childhood. Prognosis is quite variable, ranging from spontaneous regression to aggressive behavior with wide metastatization, high mortality, and limited therapeutic options. Radiotheranostics combines a radiopharmaceutical pair in a unique approach, suitable both for diagnosis and therapy. For many years, metaiodobenzylguanidine (MIBG), labeled with 123I for imaging or 131I for therapy, has represented the main theranostic agent in NB, since up to 90% of NB incorporates the aforementioned radiopharmaceutical. In recent years, novel theranostic agents hold promise in moving the field of NB radiotheranostics forward. In particular, SarTATE, consisting of octreotate targeting somatostatin receptors, has been applied with encouraging results, with 64Cu-SARTATE being used for disease detection and with 67Cu-SARTATE being used for therapy. Furthermore, recent evidence has highlighted the potential of targeted alpha therapy (TAT) for treating cancer by virtue of alpha particles’ high ionizing density and high probability of killing cells along their track. On this path, 211At-astatobenzylguanidine (MABG) has been developed as a potential agent for TAT and is actually under evaluation in preclinical NB models. In this review, we performed a web-based and desktop literature research concerning radiotheranostic approaches in NB, covering both the radiopharmaceuticals already implemented in clinical practice (i.e.,123/1311-MIBG) and those still in a preliminary or preclinical phase.