⁴⁴Sc has favorable properties for cancer diagnosis using Positron Emission Tomography (PET) making it a promising candidate for application in nuclear medicine. The implementation of its production with existing compact medical cyclotrons would mean the next essential milestone in the development of this radionuclide. While the production and application of ⁴⁴Sc has been comprehensively investigated, the development of specific targetry and irradiation methods is of paramount importance. As a result, the target was optimized for the ⁴⁴Ca(p,n)⁴⁴Sc nuclear reaction using CaO instead of CaCO₃, ensuring decrease in target radioactive degassing during irradiation and increased radionuclidic yield. Irradiations were performed at the research cyclotron at the Paul Scherrer Institute (~11 MeV, 50 µA, 90 min) and the medical cyclotron at the University of Bern (~13 MeV, 10 µA, 240 min), with yields varying from 200 MBq to 16 GBq. The development of targetry, chemical separation as well as the practical issues and implications of irradiations, are analyzed and discussed. As a proof-of-concept study, the ⁴⁴Sc produced at the medical cyclotron was used for a preclinical study using a previously developed albumin-binding prostate-specific membrane antigen (PSMA) ligand. This work demonstrates the feasibility to produce ⁴⁴Sc with high yields and radionuclidic purity using a medical cyclotron, equipped with a commercial solid target station.

Targeted radionuclide therapy with ¹⁷⁷Lu- and ⁹⁰Y-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. ⁴⁷Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy β⁻-particles. In this study, ⁴⁷Sc was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of ¹⁷⁷Lu-folate and ⁹⁰Y-folate, respectively. In vitro, ⁴⁷Sc-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to ¹⁷⁷Lu-folate, but ⁹⁰Y-folate was more potent at equal activities due to the higher energy of emitted β⁻-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with ⁴⁷Sc-folate (12.5 MBq), ¹⁷⁷Lu-folate (10 MBq), and ⁹⁰Y-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, ⁴⁷Sc is likely to be comparable to ¹⁷⁷Lu when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with ⁴⁴Sc or ⁴³Sc as a diagnostic match, enabling the realization of radiotheragnostics in future.

"Clickable" organic electrochemical transistors (OECTs) allow the reliable and straightforward functionalization of electronic devices through the well-known click chemistry toolbox. In this work, we study various aspects of the click chemistry-based interface engineering of "clickable" OECTs. First, different channel architectures are investigated, showing that PEDOT-N₃ films can properly work as a channel of the transistors. Furthermore, the Cu(I)-catalyzed click reaction of ethynyl-ferrocene is studied under different reaction conditions, endowing the spatial control of the functionalization. The strain-promoted and catalyst-free cycloaddition of a dibenzocyclooctyne-derivatized poly-l-lysine (PLL-DBCO) is also performed on the OECTs and validated by a fiber optic (FO)-SPR setup. The further immobilization of an azido-modified HD22 aptamer yields OECT-based biosensors that are employed for the recognition of thrombin. Finally, their performance is evaluated against previously reported architectures, showing higher density of the immobilized HD22 aptamer, and originating similar K_D values and higher maximum signal change upon analyte recognition.

Interfacing the surface of an organic semiconductor with biological elements is a central quest when it comes to the development of efficient organic bioelectronic devices. Here, we present the first example of "clickable" organic electrochemical transistors (OECTs). The synthesis and characterization of an azide-derivatized EDOT monomer (azidomethyl-EDOT, EDOT-N₃) are reported, as well as its deposition on Au-interdigitated electrodes through electropolymerization to yield PEDOT-N₃-OECTs. The electropolymerization protocol allows for a straightforward and reliable tuning of the characteristics of the OECTs, yielding transistors with lower threshold voltages than PEDOT-based state-of-the-art devices and maximum transconductance voltage values close to 0 V, a key feature for the development of efficient organic bioelectronic devices. Subsequently, the azide moieties are employed to click alkyne-bearing molecules such as redox probes and biorecognition elements. The clicking of an alkyne-modified PEG₄-biotin allows for the use of the avidin-biotin interactions to efficiently generate bioconstructs with proteins and enzymes. In addition, a dibenzocyclooctyne-modified thrombin-specific HD22 aptamer is clicked on the PEDOT-N₃-OECTs, showing the application of the devices toward the development of organic transistors-based biosensors. Finally, the clicked OECTs preserve their electronic features after the different clicking procedures, demonstrating the stability and robustness of the fabricated transistors.

A novel multivariable system, combining a transistor with fiber optic-based surface plasmon resonance spectroscopy with the gate electrode simultaneously acting as the fiber optic sensor surface, is reported. The dual-mode sensor allows for discrimination of mass and charge contributions for binding assays on the same sensor surface. Furthermore, we optimize the sensor geometry by investigating the influence of the fiber area to transistor channel area ratio and distance. We show that larger fiber optic tip diameters are favorable for electronic and optical signals and demonstrate the reversibility of plasmon resonance wavelength shifts after electric field application. As a proof of principle, a layer-by-layer assembly of polyelectrolytes is performed to benchmark the system against multivariable sensing platforms with planar surface plasmon resonance configurations. Furthermore, the biosensing performance is assessed using a thrombin binding assay with surface-immobilized aptamers as receptors, allowing for the detection of medically relevant thrombin concentrations.