Background/Objectives: Molecular imaging, especially PET, has advanced significantly, shifting from metabolic radiotracers like 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG to target-specific probes. Among these, αvβ6-integrin has emerged as a promising target in cancer and non-cancer diseases. This review focuses on the radiochemical properties and initial clinical applications of the [68Ga]Ga-Trivehexin PET probe. Methods: The literature review on [68Ga]Ga-Trivehexin systematically evaluated both preclinical and clinical studies, with particular emphasis on its radiochemical characteristics and preliminary clinical applications, while highlighting advancements, associated challenges, and the potential for future developments in the field. Results: This study highlights the significant advancements achieved with [68Ga]Ga-Trivehexin in the field of molecular imaging. The optimized multimeric system has substantially enhanced the radiotracer’s pharmacokinetic properties, binding affinity, and selectivity for αvβ6 integrin, demonstrating up to an 18-fold improvement compared to previous monomeric tracers. The synthesis protocol has been refined to achieve high radiochemical purity (>95%), essential for safe clinical use. Preliminary clinical applications, particularly in head and neck cancer (HNC) and pancreatic ductal adenocarcinoma (PDAC), have shown promising results, with high detection rates and improved differential diagnosis compared to [18F]FDG. Furthermore, [68Ga]Ga-Trivehexin PET/CT has shown potential in non-oncological conditions, such as idiopathic pulmonary fibrosis (IPF) and primary hyperthyroidism, suggesting broader clinical applicability. Conclusions: [68Ga]Ga-Trivehexin is a promising PET probe for imaging αvβ6-integrin in cancers and non-oncological diseases like idiopathic pulmonary fibrosis (IPF) and primary hyperparathyroidism (PHP).

⁶⁴Cu is gaining recognition not only for its diagnostic capabilities in nuclear medical imaging but also for its therapeutic and theranostic potential. The simultaneous βˉ and Auger emissions of ⁶⁴Cu can be utilized to induce a therapeutic effect on cancerous lesions. The finding of the exceptional biodistribution characteristics of the radionuclide ⁶⁴Cu, when administered as basic copper ions, has highlighted its potential therapeutic application in cancer treatment. Preclinical and clinical research on the effectiveness of [⁶⁴Cu]CuCl₂ as a theranostic radiopharmaceutical has commenced only in the past decade. Current clinical studies are increasingly demonstrating the high specificity and uptake of [⁶⁴Cu]Cu²⁺ by malignant tissues during early cancer progression, indicating its potential for early cancer diagnosis across various organs. This short review aims to present the latest preclinical studies involving [⁶⁴Cu]CuCl₂, offering valuable insights for researchers planning new in vitro and in vivo studies to explore the theranostic potential of [⁶⁴Cu]Cu²⁺.

Endometriosis is a highly prevalent, chronic gynecological disorder characterized by the ectopic presence of endometrial-like tissue, driving significant morbidity and chronic pelvic pain. Pathologically, it is increasingly recognized as a fibro-inflammatory condition involving extensive tissue remodeling and fibrosis. Current conventional imaging modalities, including ultrasound and MRI, are primarily morphological, while standard molecular imaging using Positron Emission Tomography (PET) tracers has shown limited diagnostic utility. [¹⁸F]Fluorodeoxyglucose (FDG) suffers from high physiological uptake in pelvic organs and inconsistent detection of lesions. Receptor-based tracers like [⁶⁸Ga]Ga-DOTATATE have demonstrated uncertain efficacy. In contrast, radiopharmaceuticals targeting the Fibroblast Activation Protein (FAP) offer a promising molecular approach. FAP is specifically overexpressed by activated fibroblasts present in the stroma of endometriotic lesions, correlating significantly with tissue fibrosis (collagen content) and local immune infiltration (e.g., CD68 macrophages). This comprehensive review analyzes the landscape of radiopharmaceuticals for endometriosis imaging, contrasting the specific limitations of traditional metabolic and receptor agents with the molecular rationale and emerging evidence supporting the use of FAP Inhibitors (FAPI), positioning them as crucial, non-invasive tools for the future diagnosis and management of this challenging disease.

The present study investigates the possible use of manganese (Mn)-based liposomal formulations for diagnostic applications in imaging techniques such as magnetic resonance imaging (MRI), with the aim of overcoming the toxicity limitations associated with the use of free Mn²⁺. Specifically, anionic liposomes carrying two model Mn(II)-based compounds, MnCl₂ (MC) and Mn(HMTA) (MH), were prepared and characterised in terms of morphology, size, loading capacity, and in vitro activity. Homogeneous dispersions characterised mainly by unilamellar vesicles were obtained; furthermore, no differences in size and morphology were detected between unloaded and Mn-loaded vesicles. The encapsulation efficiency of MC and MH was evaluated on extruded liposomes by means of ICP-OES analysis. The obtained results showed that both MC and MH are almost completely retained by the lipid portion of liposomes (LPs), with encapsulation efficiencies of 99.7% for MC and 98.8% for MH. The magnetic imaging properties of the produced liposomal formulations were investigated for application in a potential preclinical scenario by collecting magnetic resonance images of a phantom designed to compare the paramagnetic contrast properties of free MC and MH compounds and the corresponding manganese-containing liposome dispersions. It was found that both LP-MC and LP-MH at low concentrations (0.5 mM) show better contrast (contrast-to-noise ratios of 194 and 209, respectively) than solutions containing free Mn at the same concentrations (117 and 134, respectively) and are safe to use on human cells at the selected dose. Taken together, the results of this comparative analysis suggest that these liposome-containing Mn compounds might be suitable for diagnostic purposes.

Background/Objectives: Intrinsic genetic instability and the marked heterogeneity of malignant cell populations represent significant clinical challenges in oncology, often limiting the efficacy of conventional receptor-targeted and antigen-based therapies. To overcome these limitations, [⁶⁴Cu]CuCl₂ has emerged as a particularly promising theranostic agent because it combines PET imaging (β⁺ emission) with therapeutic effects (β⁻ particles and Auger electrons). In particular, Auger electrons, when delivered to the cell nucleus, induce severe DNA damage due to their high linear energy transfer and very short tissue range. This work aimed to deepen existing preclinical knowledge by providing a comprehensive in vitro analysis of the interactions of [⁶⁴Cu]CuCl₂ with various human cancer cell lines—specifically, the breast adenocarcinoma (MDAf-MB-231) and gastric carcinoma (NCI-N87) cell lines—and a healthy control (IMR-90 normal human fetal lung fibroblasts). Methods: We focused on evaluating cellular uptake, subcellular localization, impact on metabolic activity, and induction of apoptosis. Cell lines (MDA-MB-231, NCI-N87, IMR-90) were exposed to increasing activities of [⁶⁴Cu]CuCl₂ (10, 100, and 250 µCi/mL). Uptake was assessed in both nuclear and cytoplasmic compartments after 4 h. Metabolic activity and apoptosis/necrosis were evaluated at 96 and 120 h post-treatment. Results: Tumor cell lines demonstrated significantly higher [⁶⁴Cu]CuCl₂ uptake, particularly at the nuclear level, compared to healthy controls. A marked decrease in metabolic activity and an increase in apoptosis were observed in MDA-MB-231 and NCI-N87 cells (from 50% to 90% and 5% to 60% apoptosis, respectively). In contrast, IMR-90 cells exhibited minimal cytotoxic response (≤20%), suggesting a preferential response in the malignant cell models tested. Conclusions: [⁶⁴Cu]CuCl₂ induced distinct patterns of intracellular accumulation and biological response among the investigated cell models, with cancer cells displaying greater nuclear uptake and apoptotic susceptibility than non-malignant cells. These findings provide a high-resolution radiobiological baseline and microdosimetric validation, supporting the rigorous design of future, dedicated in vivo preclinical investigations to evaluate the translational potential of ionic [⁶⁴Cu]CuCl₂.