Prostate-specific membrane antigen (PSMA) has proven to be an important target for diagnostic imaging in prostate cancer. As PSMA is overexpressed on the surface of prostate cancer cells, numerous targeted PSMA ligands have been developed. The emergence of PSMA targeting based on small molecules, such as the PSMA-11 ligand (or PSMA-HBED-CC), has led to breakthroughs, such as [68Ga]Ga-PSMA-11, for positron emission tomography (PET) imaging of biochemically recurrent or metastatic castration-resistant prostate cancer (mCRPC). In addition, the recent approval of [177Lu]Lu-PSMA-617 for the treatment of adult patients with PSMA-positive mCRPC represents an important milestone in prostate cancer therapy. These advances underscore the growing confidence in the use of PSMA-targeted radiopharmaceuticals for the diagnosis and treatment of prostate cancer patients. PSMA-targeted radiopharmaceuticals have been shown to significantly impact treatment planning and clinical decision-making and facilitate the customisation of treatment regimens.

Molecular imaging has undergone significant development in recent years for its excellent ability to image and quantify biologic processes at cellular and molecular levels. Its application is of significance in cardiovascular diseases, particularly in diagnosing them at early stages. Atherosclerosis is a complex, chronic, and progressive disease that can lead to serious consequences such as heart strokes or infarctions. Attempts have been made to detect atherosclerosis with molecular imaging modalities. Not only do imaging modalities develop rapidly, but research of relevant nanomaterials as imaging probes has also been increasingly studied in recent years. This review focuses on the latest developments in the design and synthesis of probes that can be utilized in computed tomography, positron emission tomography, magnetic resonance imaging, ultrasound imaging, photoacoustic imaging and combined modalities. The challenges and future developments of nanomaterials for molecular imaging modalities are also discussed.

Atherosclerosis is a chronic inflammatory condition of the arteries and represents the primary cause of various cardiovascular diseases. Despite ongoing progress, finding effective anti-inflammatory therapeutic strategies for atherosclerosis remains a challenge. Here, we assessed the potential of molecular magnetic resonance imaging (MRI) to visualize the effects of 01BSUR, an anti-interleukin-1β monoclonal antibody, for treating atherosclerosis in a murine model. Male apolipoprotein E-deficient mice were divided into a therapy group (01BSUR, 2 × 0.3 mg/kg subcutaneously, n = 10) and control group (no treatment, n = 10) and received a high-fat diet for eight weeks. The plaque burden was assessed using an elastin-targeted gadolinium-based contrast probe (0.2 mmol/kg intravenously) on a 3 T MRI scanner. T1-weighted imaging showed a significantly lower contrast-to-noise (CNR) ratio in the 01BSUR group (pre: 3.93042664; post: 8.4007067) compared to the control group (pre: 3.70679168; post: 13.2982156) following administration of the elastin-specific MRI probe (p < 0.05). Histological examinations demonstrated a significant reduction in plaque size (p < 0.05) and a significant decrease in plaque elastin content (p < 0.05) in the treatment group compared to control animals. This study demonstrated that 01BSUR hinders the progression of atherosclerosis in a mouse model. Using an elastin-targeted MRI probe, we could quantify these therapeutic effects in MRI.

Molecular ultrasound imaging with actively targeted microbubbles (MB) proved promising in preclinical studies but its clinical translation is limited. To achieve this, it is essential that the actively targeted MB can be produced with high batch-to-batch reproducibility with a controllable and defined number of binding ligands on the surface. In this regard, poly (n-butyl cyanoacrylate) (PBCA)-based polymeric MB have been used for US molecular imaging, however, ligand coupling was mostly done via hydrolysis and carbodiimide chemistry, which is a multi-step procedure with poor reproducibility and low MB yield. Herein, we developed a single-step coupling procedure resulting in high MB yields with minimal batch-to-batch variation. Actively targeted PBCA-MB were generated using an aminolysis protocol, wherein amine-containing cRGD was added to the MB using lithium methoxide as a catalyst. We confirmed the successful conjugation of cRGD on the MB surface, while preserving their structure and acoustic signal. Compared to the conventional hydrolysis protocol, aminolysis resulted in higher MB yields and better reproducibility of coupling efficiency. Optical imaging revealed that under flow conditions, cRGD- and rhodamine-labelled MB, generated by aminolysis, specifically bind to tumor necrosis factor-alpha (TNF-α) activated endothelial cells in vitro. Furthermore, US molecular imaging demonstrated a markedly higher binding of the cRGD-MB than of control MB in TNF-α activated mouse aortas and 4T1 tumors in mice. Thus, using the aminolysis based conjugation approach, important refinements on the production of cRGD-MB could be achieved that will facilitate the production of clinical-scale formulations with excellent binding and ultrasound imaging performance.

BACKGROUND: To date, radical surgery remains the best curative option in patients with early-stage lung cancer. In patients with small lung lesions, video-assisted thoracic surgery (VATS) should be increasingly chosen as a fundamental alternative to thoracotomy as it is associated with less postoperative pain and better quality of life. This scenario necessarily increases the need for thoracic surgeons to implement new localization techniques. The conventional near-infrared (NIR) indocyanine green (ICG) method demonstrated a significant limitation in deep cancer recognition, principally due to its intrinsic low-depth tissue penetration. Similarly, the lymph-node sentinel approach conducted by the ICG method was demonstrated to be inefficient, mainly due to the non-specificity of the tracker and the irregular pathway of pulmonary lymph node drainage. Our study aims to evaluate the effectiveness of Cetuximab- IRDye800CW in marking lung nodules and mediastinal lymph nodes.
METHODS: This study is defined as an open-label, single-arm, single-stage phase II trial evaluating the effectiveness of Cetuximab-IRDye800CW in detecting tumors and lymph-node metastases in patients with lung cancer who are undergoing video-assisted thoracic surgery (VATS). Cetuximab is a monoclonal antibody that binds, inhibits, and degrade the EGFR. The IRDye® 800CW, an indocyanine-type NIR fluorophore, demonstrated enhanced tissue penetration compared to other NIR dyes. The combination with the clinical approved monoclonal antibody anti-epidermal growth factor EGFR Cetuximab (Cetuximab-IRDye800) has shown promising results as a specific tracker in different cancer types (i.e., brain, pancreas, head, and neck). The study\'s primary outcome is focused on the proportion of patients with lung nodules detected during surgery using an NIR camera. The secondary outcomes include a broad spectrum of items, including the proportion of patients with detection of unexpected cancer localization during surgery by NIR camera and the proportion of patients with negative surgical margins, the evaluation of the time spawns between the insertion of the NIR camera and the visualization of the nodule and the possible morbidity of the drug assessed during and after the drug infusion.
BACKGROUND: This trial has been approved by the Ethical Committee of Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino (Torino, Italy) and by the Italian Medicines Agency (AIFA). Findings will be written as methodology papers for conference presentations and published in peer-reviewed journals. The Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, the University of Torino, and the AIRC Public Engagement Divisions will help identify how best to publicize the findings.Trial registration EudraCT 202,100,645,430.
RESULTS: gov NCT06101394 (October 23, 2023).

BACKGROUND: Positron emission tomography (PET) traditionally uses coincident annihilation photons emitted from a positron interacting with an electron to localize cancer within the body. The formation of positronium (Ps), a bonded electron-positron pair, has not been utilized in clinical applications of PET due to the need to detect either the emission of a prompt gamma ray or the decay of higher-order coincident events. Assessment of the lifetime of the formed Ps, however, can potentially yield additional diagnostic information of the surrounding tissue because Ps properties vary due to void size and molecular composition. To assess the feasibility of measuring Ps lifetimes with a PET scanner, experiments were performed in a Biograph Vision Quadra (Siemens Healthineers). Quadra is a long-axial field-of-view (LA-FOV) PET scanner capable of producing list-mode data from single interaction events.
RESULTS: Ortho-Ps (o-Ps) lifetimes were measured for quartz-glass and polycarbonate samples using a 22 Na positron source. Results produced o-Ps lifetimes of 1.538 ± 0.036 ns for the quartz glass and 1.927 ± 0.042 ns for the polycarbonate. Both o-Ps lifetimes were determined using a double-exponential fit to the time-difference distribution between the emission of a prompt gamma ray and the annihilation of the correlated positron. The measured values match within a single standard deviation of previously published results. The quartz-glass samples were additional measured with 82 Rb , 68 Ga and 124 I to validate the lifetime using clinically available sources. A double-exponential fit was initially chosen as a similar methodology to previously published works, however, an exponentially-modified Gaussian distribution fit to each lifetime more-accurately models the data. A Bayesian method was used to estimate the variables of the fit and o-Ps lifetime results are reported using this methodology for the three clinical isotopes: 1.59 ± 0.03 ns for 82 Rb , 1.58 ± 0.07 ns for 68 Ga and 1.62 ± 0.01 ns for 124 I . The impact of scatter and attenuation on the o-Ps lifetime was also assessed by analyzing a water-filled uniform cylinder (20 ϕ × 30 cm 3 ) with an added 82 Rb solution. Lifetimes were extracted for various regions of the cylinder and while there is a shape difference in the lifetime due to scatter, the extracted o-Ps lifetime of the water, 1.815 ± 0.013 ns, agrees with previously published results.
CONCLUSIONS: Overall, the methodology presented in this manuscript demonstrates the repeatability of Ps lifetime measurements with clinically available isotopes in a commercially-available LA-FOV PET scanner. This validation work lays the foundation for future in-vivo patient scans with Quadra.

Understanding the role of chemokine receptors in health and disease has been of increasing interest in recent years. Chemokine receptor CXCR4 has been extensively studied because of its defined role in immune cell trafficking, HIV infection, inflammatory diseases, and cancer progression. We have developed high affinity rigidified CXCR4 antagonists that incorporate metal ions to optimize the binding interactions with the aspartate side chains at the extracellular surface of the CXCR4 chemokine receptor and increase the residence time. Cross- and side-bridged tetraazamacrocylic complexes offer significant advantages over the non-bridged molecular structures in terms of receptor affinity, potential for radiolabelling, and use in therapeutic applications. Our investigation has been extended to the influence of the ring size on bridged tetraazamacrocyclic compounds with the addition of two novel chelators (bis-cross-bridged homocyclen and bis-cross-bridged cyclen) to compare to the bis-bridged cyclam, along with novel metal complexes formed with copper(II) or zinc(II). The in vitro biological assays showed that all of the zinc(II) complexes are high affinity antagonists with a marked increase in CXCR4 selectivity for the bis-cross-bridged cyclen complex, whereas the properties of the copper(II) complexes are highly dependent on metal ion geometry. X-ray crystal structural data and DFT computational studies allow for the rationalisation of the relative affinities and the aspartate residue interactions on the protein surface. Changing the ring size from 14-membered can increase the selectivity for the CXCR4 receptor whilst retaining potent inhibitory activity, improving the key pharmacological characteristics.

Non-tumorous kidney diseases include a variety of conditions affecting both the structure and function of the kidneys, thereby causing a range of health-related problems. Positron emission tomography/computed tomography (PET/CT) has emerged as a potential diagnostic tool, offering a multifaceted approach to evaluating non-tumorous kidney diseases. Its clinical significance extends beyond its conventional role in cancer imaging, enabling a comprehensive assessment of renal structure and function. This review explores the diverse applications of PET/CT imaging in the evaluation of non-cancerous kidney diseases. It examines PET/CT\'s role in assessing acute kidney injuries, including acute pyelonephritis and other forms of nephritis, as well as chronic conditions such as immune complex-mediated glomerulonephritis and chronic kidney disease. Additionally, the review delves into PET/CT\'s utility in evaluating complications in renal transplant recipients, identifying renal histiocytosis and detecting renal amyloidosis. The current review aims to promote further research and technological advancements to popularize PET/CT\'s clinical utility in diagnosing and treating non-tumorous kidney diseases.

BACKGROUND: Cardiovascular diseases, particularly myocardial ischemia from coronary artery obstruction, remain a leading cause of global morbidity. This review explores cardiac molecular magnetic resonance imaging (mMRI) and other molecular imaging techniques for the evaluation of myocardial ischemia, scarring, and viability.
RESULTS: mMRI imaging methods provide detailed information on myocardial ischemia, edema, and scar tissue using techniques like cine imaging, T1 and T2 mapping, and gadolinium-based contrast agents. These methods enable the precise assessment of the myocardial tissue properties, crucial in diagnosing and treating cardiovascular diseases. Advanced techniques, such as the T1ρ and RAFFn methods, might provide enhanced contrast and sensitivity for the detection of myocardial scarring without contrast agents. Molecular probes, including gadolinium-based and protein-targeted contrast agents, improve the detection of molecular changes, facilitating early diagnosis and personalized treatment. Integrating MRI with positron emission tomography (PET) combines the high spatial and temporal resolution with molecular and functional imaging.
CONCLUSIONS: Recent advancements in mMRI and molecular imaging have changed the evaluation of myocardial ischemia, scarring, and viability. Despite significant progress, extensive research is needed to validate these techniques clinically and further develop imaging methods for better diagnostic and prognostic outcomes.

Small molecules are highly relevant targets for detection and quantification. They are also used to diagnose and monitor the progression of disease and infectious processes and track the presence of contaminants. Fluorogenic RNA-based biosensors (FRBs) represent an appealing solution to the problem of detecting these targets. They combine the portability of molecular systems with the sensitivity and multiplexing capacity of fluorescence, as well as the exquisite ligand selectivity of RNA aptamers. In this review, we first present the different sensing and reporting aptamer modules currently available to design an FRB, together with the main methodologies used to discover modules with new specificities. We next introduce and discuss how both modules can be functionally connected prior to exploring the main applications for which FRB have been used. Finally, we conclude by discussing how using alternative nucleotide chemistries may improve FRB properties and further widen their application scope.