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Significance: Standardization of fluorescence molecular imaging (FMI) is critical for ensuring quality control in guiding surgical procedures. To accurately evaluate system performance, two metrics, the signal-to-noise ratio (SNR) and contrast, are widely employed. However, there is currently no consensus on how these metrics can be computed. Aim: We aim to examine the impact of SNR and contrast definitions on the performance assessment of FMI systems. Approach: We quantified the SNR and contrast of six near-infrared FMI systems by imaging a multi-parametric phantom. Based on approaches commonly used in the literature, we quantified seven SNRs and four contrast values considering different background regions and/or formulas. Then, we calculated benchmarking (BM) scores and respective rank values for each system. Results: We show that the performance assessment of an FMI system changes depending on the background locations and the applied quantification method. For a single system, the different metrics can vary up to ∼ 35 dB (SNR), ∼ 8.65 a . u . (contrast), and ∼ 0.67 a . u . (BM score). Conclusions: The definition of precise guidelines for FMI performance assessment is imperative to ensure successful clinical translation of the technology. Such guidelines can also enable quality control for the already clinically approved indocyanine green-based fluorescence image-guided surgery.

Asunto(s)

Benchmarking , Imagen Molecular , Imagen Óptica , Fantasmas de Imagen , Relación Señal-Ruido , Imagen Molecular/métodos , Imagen Molecular/normas , Imagen Óptica/métodos , Imagen Óptica/normas , Procesamiento de Imagen Asistido por Computador/métodos

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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.

Asunto(s)

Aterosclerosis , Imagen Molecular , Humanos , Aterosclerosis/diagnóstico por imagen , Imagen Molecular/métodos , Nanoestructuras , Animales , Tomografía de Emisión de Positrones/métodos , Técnicas Fotoacústicas/métodos , Nanopartículas/química

RESUMEN

INTRODUCTION: 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 AND ANALYSIS: 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. ETHICS AND DISSEMINATION: 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. CLINICALTRIALS: gov NCT06101394 (October 23, 2023).

Asunto(s)

Neoplasias Pulmonares , Imagen Molecular , Cirugía Torácica Asistida por Video , Humanos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Cirugía Torácica Asistida por Video/métodos , Imagen Molecular/métodos , Espectroscopía Infrarroja Corta/métodos , Cetuximab/uso terapéutico , Cetuximab/administración & dosificación , Verde de Indocianina/administración & dosificación , Metástasis Linfática , Femenino , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía

RESUMEN

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.

Asunto(s)

Enbucrilato , Microburbujas , Imagen Molecular , Ultrasonografía , Animales , Enbucrilato/química , Ratones , Imagen Molecular/métodos , Ultrasonografía/métodos , Humanos , Medios de Contraste/química , Femenino , Células Endoteliales de la Vena Umbilical Humana , Ratones Endogámicos BALB C , Línea Celular Tumoral , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers.

Asunto(s)

Enzima Convertidora de Angiotensina 2 , COVID-19 , Imagen Molecular , SARS-CoV-2 , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , Imagen Molecular/métodos , COVID-19/metabolismo , COVID-19/diagnóstico por imagen , SARS-CoV-2/metabolismo , Radiofármacos/química , Radiofármacos/metabolismo , Animales , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodos

RESUMEN

Early-stage diagnosis of liver cancer is challenging, with an overall poor prognosis. The tumor microenvironment of primary liver cancer is complex, exhibiting significant heterogeneity both interpersonally and intratumorally. Therefore, it is of paramount importance to dynamically analyze biological markers in the tumor microenvironment of primary liver cancer in vivo. In recent years, significant progress has been made in the imaging diagnosis and treatment of liver cancer with the development of molecular imaging. Molecular imaging techniques utilize specific nano-imaging probes to evaluate pathological changes of liver cancer at the molecular and cellular levels in real-time. These techniques enable precise imaging to reveal key molecular biomarkers involved in the occurrence and progression of liver cancer, exploring their associations with cancer progression and outcomes. This article focuses on molecular imaging, emphasizing the current research status and latest advancements in the field of liver cancer diagnosis and therapy using techniques such as CT, MRI, optical imaging, PET imaging, and multimodal imaging. It also identifies important future directions and significant challenges for further development.

Asunto(s)

Neoplasias Hepáticas , Imagen por Resonancia Magnética , Imagen Molecular , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico , Humanos , Imagen Molecular/métodos , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones/métodos , Imagen Multimodal/métodos , Tomografía Computarizada por Rayos X/métodos , Microambiente Tumoral , Biomarcadores de Tumor

RESUMEN

The incorporation of gold nanoparticles (GNPs) into retinal imaging signifies a notable advancement in ophthalmology, offering improved accuracy in diagnosis and patient outcomes. This review explores the synthesis and unique properties of GNPs, highlighting their adjustable surface plasmon resonance, biocompatibility, and excellent optical absorption and scattering abilities. These features make GNPs advantageous contrast agents, enhancing the precision and quality of various imaging modalities, including photoacoustic imaging, optical coherence tomography, and fluorescence imaging. This paper analyzes the unique properties and corresponding mechanisms based on the morphological features of GNPs, highlighting the potential of GNPs in retinal disease diagnosis and management. Given the limitations currently encountered in clinical applications of GNPs, the approaches and strategies to overcome these limitations are also discussed. These findings suggest that the properties and efficacy of GNPs have innovative applications in retinal disease imaging.

Asunto(s)

Oro , Nanopartículas del Metal , Imagen Óptica , Retina , Tomografía de Coherencia Óptica , Oro/química , Nanopartículas del Metal/química , Humanos , Imagen Óptica/métodos , Retina/diagnóstico por imagen , Retina/metabolismo , Tomografía de Coherencia Óptica/métodos , Enfermedades de la Retina/diagnóstico por imagen , Enfermedades de la Retina/diagnóstico , Animales , Imagen Molecular/métodos , Medios de Contraste/química

Asunto(s)

Imagen Molecular , Humanos , Animales , Imagen Molecular/métodos

RESUMEN

Localized protein translation occurs through trafficking of mRNAs and protein translation machineries to different compartments of the cell, leading to rapid on-site synthesis of proteins in response to signaling cues. The spatiotemporally precise nature of the local translation process necessitates continual developments of technologies reviewed herein to visualize and map biomolecular components and the translation process with better spatial and temporal resolution and with fewer artifacts. We also discuss approaches to control local translation, which can serve as a design paradigm for subcellular genetic devices for eukaryotic synthetic biology.

Asunto(s)

Biosíntesis de Proteínas , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Imagen Molecular/métodos , Animales , Biología Sintética/métodos , Proteínas/metabolismo

RESUMEN

The ability to image tissues in three dimensions (3D) with label-free molecular contrast at the mesoscale would be a valuable capability in biology and biomedicine. Here, we introduce Raman spectral projection tomography (RSPT) for volumetric molecular imaging with optical sub-millimeter spatial resolution. We have developed a RSPT imaging instrument capable of providing 3D molecular contrast in transparent and semi-transparent samples. We also created a computational pipeline for multivariate reconstruction to extract label-free spatial molecular information from Raman projection data. Using these tools, we demonstrate imaging and visualization of phantoms of various complex shapes with label-free molecular contrast. Finally, we apply RSPT as a tool for imaging of molecular gradients and extracellular matrix heterogeneities in fixed and living tissue-engineered constructs and explanted native cartilage tissues. We show that there exists a favorable balance wherein employing Raman spectroscopy, with its advantages in live cell imaging and label-free molecular contrast, outweighs the reduction in imaging resolution and blurring caused by diffuse photon propagation. Thus, RSPT imaging opens new possibilities for label-free molecular monitoring of tissues.

Asunto(s)

Imagenología Tridimensional , Imagen Molecular , Fantasmas de Imagen , Espectrometría Raman , Espectrometría Raman/métodos , Imagenología Tridimensional/métodos , Animales , Imagen Molecular/métodos , Ingeniería de Tejidos/métodos , Humanos , Tomografía/métodos , Cartílago/diagnóstico por imagen , Cartílago/metabolismo , Matriz Extracelular/metabolismo , Ratones

RESUMEN

Plant health, which affects the nutritional quality and safety of derivative food products, is influenced by symbiotic interactions with microorganisms. These interactions influence the local molecular profile at the tissue level. Therefore, studying the distribution of molecules within plants, microbes, and plant-based food is crucial to assess plant health, ensure the safety and quality of the agricultural products that become part of our food supply, and plan agricultural management practices. Within this framework, the molecular distribution within plant-based samples can be visualized with mass spectrometry imaging (MSI). This review describes key MSI methodologies, highlighting the role they play in unraveling the localization of metabolites, lipids, proteins, pigments, and elemental components across plants, microbes, and food products. Furthermore, investigations that involve multimodal molecular imaging approaches combining MSI with other imaging techniques are described. The advantages and limitations of the different MSI techniques that influence their applicability in diverse agro-food studies are described to enable informed choices for tailored analyses. For example, some MSI technologies involve meticulous sample preparation while others compromise spatial resolution to gain throughput. Key parameters such as sensitivity, ionization bias and fragmentation, reference database and compound class specificity are described and discussed in this review. With the ongoing refinements in instrumentation, data analysis, and integration of complementary techniques, MSI deepens our insight into the molecular biology of the agricultural ecosystem. This in turn empowers the quest for sustainable and productive agricultural practices.

Asunto(s)

Espectrometría de Masas , Plantas , Plantas/química , Plantas/metabolismo , Espectrometría de Masas/métodos , Análisis de los Alimentos/métodos , Imagen Molecular/métodos

RESUMEN

BACKGROUND: Early detection and treatment are effective methods for the management of oral squamous cell carcinoma (OSCC), which can be facilitated by the detection of tumor-specific OSCC biomarkers. The epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) are important therapeutic targets for OSCC. Multispectral fluorescence molecular imaging (FMI) can facilitate the detection of tumor multitarget expression with high sensitivity and safety. Hence, we developed Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes, in combination with multispectral FMI, to sensitively and noninvasively identify EGFR and PD-L1 expression for the detection and comprehensive treatment of OSCC. METHODS: The expression of EGFR and PD-L1 was analyzed using bioinformatics data sources and specimens. Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes were developed and tested on preclinical OSCC cell line and orthotopic OSCC mouse model, fresh OSCC patients' biopsied samples, and further clinical mouthwash trials were conducted in OSCC patients. RESULTS: EGFR and PD-L1 were specifically expressed in human OSCC cell lines and tumor xenografts. Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes can specifically target to the tumor sites in an in situ human OSCC mouse model with good safety. The detection sensitivity and specificity of Nimotuzumab-ICG in patients were 96.4% and 100%, and 95.2% and 88.9% for Atezolizumab-Cy5.5. CONCLUSIONS: EGFR and PD-L1 are highly expressed in OSCC, the combination of which is important for a precise prognosis of OSCC. EGFR and PD-L1 expression can be sensitively detected using the newly synthesized multispectral fluorescence imaging probes Nimotuzumab-ICG and Atezolizumab-Cy5.5, which can facilitate the sensitive and specific detection of OSCC and improve treatment outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100045738. Registered 23 April 2021, https://www.chictr.org.cn/bin/project/edit?pid=125220.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Antígeno B7-H1 , Carcinoma de Células Escamosas , Receptores ErbB , Neoplasias de la Boca , Imagen Óptica , Humanos , Antígeno B7-H1/metabolismo , Animales , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/diagnóstico , Imagen Óptica/métodos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Ratones , Femenino , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/diagnóstico , Masculino , Línea Celular Tumoral , Persona de Mediana Edad , Imagen Molecular/métodos , Biomarcadores de Tumor/metabolismo

RESUMEN

All the nanotechnological devices designed for medical purposes have to deal with the common requirement of facing the complexity of a living organism. Therefore, the development of these nanoconstructs must involve the study of their structural and functional interactions and the effects on cells, tissues, and organs, to ensure both effectiveness and safety. To this aim, imaging techniques proved to be extremely valuable not only to visualize the nanoparticles in the biological environment but also to detect the morphological and molecular modifications they have induced. In particular, histochemistry is a long-established science able to provide molecular information on cell and tissue components in situ, bringing together the potential of biomolecular analysis and imaging. The present review article aims at offering an overview of the various histochemical techniques used to explore the impact of novel nanoproducts as therapeutic, reconstructive and diagnostic tools on biological systems. It is evident that histochemistry has been playing a leading role in nanomedical research, being largely applied to single cells, tissue slices and even living animals.

Asunto(s)

Imagen Molecular , Nanomedicina , Humanos , Animales , Imagen Molecular/métodos , Nanomedicina/métodos , Nanopartículas/química , Histocitoquímica/métodos

RESUMEN

Selective autophagy of the endoplasmic reticulum (ER-phagy) is a mechanism that is necessary for degrading damaged ER components and preventing cells from experiencing ER stress. Various ER-phagy receptors orchestrate this process by building protein assemblies with dedicated functions. In order to understand the molecular building principles of ER-phagy, it is important to reveal the assembly of ER-phagy receptors in a temporal and functional context. However, direct visualization is hampered by the diffraction limit in light microscopy. Super-resolution microscopy (SRM) can bypass this limitation and resolve single proteins and nanoscale protein clusters in cells. In particular, DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) is a powerful technology that can resolve individual protein clusters in cells and provide information on their molecular composition. Here, we report a step-by-step protocol on how to utilize DNA-PAINT to perform super-resolution imaging of ER-phagy receptors in fixed cells. In addition, we provide a detailed explanation of image generation, cluster analysis, and molecular quantification.

Asunto(s)

Autofagia , Retículo Endoplásmico , Retículo Endoplásmico/metabolismo , Humanos , Microscopía Fluorescente/métodos , Estrés del Retículo Endoplásmico , Procesamiento de Imagen Asistido por Computador/métodos , Animales , Imagen Molecular/métodos

RESUMEN

Occult nodal spread and metastatic disease require longstanding imaging and biochemical assessments for thyroid cancer, a disease that has a propensity for diffuse, small-volume disease. We have developed a 64Cu-labeled platelet-derived growth factor receptor α (PDGFRA) antibody for immuno-PET of PDGFRA in metastatic papillary thyroid cancer (PTC). The present work describes the discovery of small cyclic PDGFRA-targeting peptides, their binding features, and radiolabeling with positron emitter gallium-68 (68Ga) for in vitro and in vivo characterization in thyroid cancer models. Phage-display technology with two separate libraries and seven different cell lines was used through three rounds of biopanning as well as flow cytometry and comparative analysis with recombinant protein to select specific peptide sequences. Phenotypic binding analysis was completed by using phosphorylation and cell migration assays. In vitro protein binding was analyzed with thermophoresis and flow cytometry using the fluorescent-labeled PDGFRA peptide. Peptide candidates were modified with the NOTA chelator for radiolabeling with 68Ga. In vitro cell uptake was studied in various thyroid cancer cell lines. In vivo studies of 68Ga-labeled peptides included metabolic stability and PET imaging. From the original library (1013 compounds), five different peptide groups were identified based on biopanning experiments with and without the α subunit of PDGFR, leading to ∼50 peptides. Subsequent phenotypic screening revealed two core peptide sequences (CP16 and CP18) that demonstrated significant changes in the level of PDGFRA phosphorylation and cell migration. Alanine scan sublibraries were created from these two lead peptide sequences, and peptides were radiolabeled using 68Ga-GaCl3 at pH 4.5, resulting in RCP > 95% within 34-40 min, including SPE purification. Cyclic peptide CP18.5 showed the strongest effects on cell migration, flow cytometry, and binding by visual interference color assay. 68Ga-labeled PDGFRA-targeting peptides showed elevated cell and tumor uptake in models of thyroid cancer, with 68Ga-NOTA-CP18.5 being the lead candidate. However, metabolic stability in vivo was compromised for 68Ga-NOTA-CP18.5 vs 68Ga-NOTA-CP18 but without impacting tumor uptake or clearance profiles. First-generation radiolabeled cyclic peptides have been developed as novel radiotracers, particularly 68Ga-NOTA-CP18.5, for the molecular imaging of PDGFRA in thyroid cancer.

Asunto(s)

Radioisótopos de Galio , Imagen Molecular , Péptidos Cíclicos , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Humanos , Animales , Línea Celular Tumoral , Ratones , Péptidos Cíclicos/química , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Radioisótopos de Galio/química , Imagen Molecular/métodos , Tomografía de Emisión de Positrones/métodos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/metabolismo , Radiofármacos/química , Radiofármacos/farmacocinética , Cáncer Papilar Tiroideo/diagnóstico por imagen , Cáncer Papilar Tiroideo/metabolismo , Movimiento Celular , Radioisótopos de Cobre/química , Ratones Desnudos , Femenino

RESUMEN

Theranostics integrate molecular imaging and targeted radionuclide therapy for personalised cancer therapy. Theranostic treatments have shown meaningful efficacy in randomised clinical trials and are approved for clinical use in prostate cancer and neuroendocrine tumours. Brain tumours represent an unmet clinical need and theranostics might offer effective treatment options, although specific issues need to be considered for clinical development. In this Policy Review, we discuss opportunities and challenges of developing targeted radionuclide therapies for the treatment of brain tumours including glioma, meningioma, and brain metastasis. The rational choice of molecular treatment targets is highlighted, including the potential relevance of different types of targeted radionuclide therapeutics, and the role of the blood-brain barrier and blood-tumour barrier. Furthermore, we discuss considerations for effective clinical trial design and conduct, as well as logistical and regulatory challenges for implementation of radionuclide therapies into neuro-oncological practice. Rational development will foster successful translation of the theranostic concept to brain tumours.

Asunto(s)

Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/terapia , Barrera Hematoencefálica , Nanomedicina Teranóstica , Medicina de Precisión , Investigación Biomédica Traslacional , Terapia Molecular Dirigida , Radiofármacos/uso terapéutico , Radioisótopos/uso terapéutico , Oncología Médica , Imagen Molecular

Asunto(s)

Imagen Molecular , Infarto del Miocardio , Humanos , Infarto del Miocardio/diagnóstico por imagen , Imagen Molecular/métodos , Tomografía de Emisión de Positrones/métodos

RESUMEN

There are several promising radiotracers used for both staging and restaging of primary and recurrent brain tumours based on various mechanisms of tracer localization in tumour cells. 68Ga-PSMA PET has extremely low background uptake in normal brain tissue and consequently high tumour-to-brain ratio making it a promising imaging radiotracer for gliomas. 68Ga-PSMA demonstrates utility in evaluating high grade glioma during both initial workup or when suspecting recurrence. Herein the authors evaluate the role of this imaging modality and the potential future it holds in the management of high grade gliomas.

Asunto(s)

Neoplasias Encefálicas , Glioma , Imagen Molecular , Neovascularización Patológica , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Humanos , Angiogénesis , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Ácido Edético/análogos & derivados , Radioisótopos de Galio/administración & dosificación , Glioma/diagnóstico por imagen , Glioma/patología , Imagen Molecular/métodos , Clasificación del Tumor , Neovascularización Patológica/diagnóstico por imagen , Oligopéptidos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos/administración & dosificación

RESUMEN

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. Here, we systematically characterized and quantified macro- and micro-calcification in a HFTC cohort using CT and 18F-sodium fluoride PET/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on 4 phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (eg, total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of mineralization activity (eg, mean standardized uptake values-SUVs). Microcalcification scores were calculated for the vasculature of 6 patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1 cm3, n = 9) and lesion volume (282.5 ± 414.8 cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the abdominal aorta, carotid, and coronaries in 50%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden.

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Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder in which patients develop sometimes large debilitating calcifications of soft tissues and blood vessels. It is caused by deficient fibroblast growth factor-23 that leads to high phosphate levels, which contributes to the calcifications. The calcifications and manifestations of this disorder have not been well characterized. We determined the mineral composition of the calcifications to be hydroxyapatite. Capitalizing on the fact fluoride can be integrated into hydroxyapatite, we used radiolabeled sodium fluoride PET/CT scans (18F-NaF PET/CT) to characterize and quantify the calcifications in 11 patients. Eighty-two percent of the patients had calcifications, with the largest located at the hips and shoulders. Micro-calcifications were found in the blood vessels of most patients, including children. The technique also enabled us to differentiate between active vs stable calcifications. This first systematic assessment of calcifications in patients with HFTC showed the utility of 18F-NaF PET/CT as a tool to identify and quantify calcifications, as well as distinguish between active and stable calcifications. This approach will inform disease progression and may prove useful for measuring response to treatment.

Asunto(s)

Calcinosis , Factor-23 de Crecimiento de Fibroblastos , Hiperfosfatemia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Calcificación Vascular , Humanos , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Calcinosis/genética , Femenino , Masculino , Hiperfosfatemia/diagnóstico por imagen , Hiperfosfatemia/patología , Hiperfosfatemia/complicaciones , Hiperfosfatemia/genética , Adulto , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/patología , Calcificación Vascular/metabolismo , Persona de Mediana Edad , Adolescente , Niño , Imagen Molecular/métodos , Hiperostosis Cortical Congénita/diagnóstico por imagen , Hiperostosis Cortical Congénita/genética , Hiperostosis Cortical Congénita/patología , Hiperostosis Cortical Congénita/complicaciones , Hiperostosis Cortical Congénita/metabolismo , Fluoruro de Sodio , Adulto Joven

RESUMEN

BACKGROUND: Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome. METHODS: In this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response. Imaging included 18F-BMS-986192 (PD-L1) PET and 18F-fluorodeoxyglucose (FDG) PET before and after nivolumab treatment. Secondary objectives included clinical and pathological response, and immune profiling of peripheral blood mononuclear cells (PBMCs) for response prediction. Baseline tumor biopsies and postnivolumab resection specimens were evaluated by histopathology. RESULTS: Grade III or higher adverse events were not observed and treatment was not delayed in relation to nivolumab administration and other study procedures. Six patients (38%) had a pathological response, of whom three (19%) had a major (≥90%) pathological response (MPR). Tumor PD-L1 PET uptake (quantified using standard uptake value) was not statistically different in patients with or without MPR (median 5.3 vs 3.4). All major responders showed a significantly postnivolumab decreased signal on FDG PET. PBMC immune phenotyping showed higher levels of CD8+ T cell activation in MPR patients, evidenced by higher baseline expression levels of PD-1, TIGIT, IFNγ and lower levels of PD-L1. CONCLUSION: Together these data support that neoadjuvant treatment of advanced-stage oral cancers with nivolumab was safe and induced an MPR in a promising 19% of patients. Response was associated with decreased FDG PET uptake as well as activation status of peripheral T cell populations.

Asunto(s)

Neoplasias de la Boca , Terapia Neoadyuvante , Humanos , Masculino , Femenino , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/patología , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Anciano , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Imagen Molecular/métodos , Nivolumab/uso terapéutico , Nivolumab/farmacología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Tomografía de Emisión de Positrones/métodos , Adulto