Artificial intelligence in cancer imaging: Clinical challenges and applications.

Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care.

Artificial intelligence-based risk stratification, accurate diagnosis and treatment prediction in gynecologic oncology.

As data-driven science, artificial intelligence (AI) has paved a promising path toward an evolving health system teeming with thrilling opportunities for precision oncology. Notwithstanding the tremendous success of oncological AI in such fields as lung carcinoma, breast tumor and brain malignancy, less attention has been devoted to investigating the influence of AI on gynecologic oncology. Hereby, this review sheds light on the ever-increasing contribution of state-of-the-art AI techniques to the refined risk stratification and whole-course management of patients with gynecologic tumors, in particular, cervical, ovarian and endometrial cancer, centering on information and features extracted from clinical data (electronic health records), cancer imaging including radiological imaging, colposcopic images, cytological and histopathological digital images, and molecular profiling (genomics, transcriptomics, metabolomics and so forth). However, there are still noteworthy challenges beyond performance validation. Thus, this work further describes the limitations and challenges faced in the real-word implementation of AI models, as well as potential solutions to address these issues.

Radiolabelled 177 Lu-Bispidine-Trastuzumab for Targeting Human Epidermal Growth Factor Receptor 2 Positive Cancers.

Radioimmunotherapy (RIT) is a promising alternative to conventional treatment options. Here, we present experimental work on the synthesis, radiochemistry, and in vivo performance of a lanthanoid-selective nonadentate bispidine ligand suitable for 177 Lu3+ ion complexation. The ligand (bisp,1) was derivatised with a photoactivatable aryl azide (ArN3 ) group as a bioconjugation handle for light-induced labelling of proteins. Quantitative radiosynthesis of [177 Lu]Lu-1+ was accomplished in 10 minutes at 40 °C. Subsequent incubation of [177 Lu]Lu-1+ with trastuzumab, followed by irradiation with light at 365 nm for 15 min, at room temperature and pH 8.0-8.3, gave the radiolabelled mAb, [177 Lu]Lu-1-azepin-trastuzumab ([177 Lu]Lu-1-mAb) in a decay-corrected radiochemical yield of 14 %, and radiochemical purity (RCP)>90 %. Stability studies and cellular binding assays in vitro using the SK-OV-3 human ovarian cancer cells confirmed that [177 Lu]Lu-1-mAb remained biological active and displayed specific binding to HER2/neu. Experiments in immunocompromised female athymic nude mice bearing subcutaneous xenograft models of SK-OV-3 tumours revealed significantly higher tumour uptake in the normal group compared with the control block group (29.8±11.4 %ID g-1 vs. 14.8±6.1 %ID g-1 , respectively; P-value=0.037). The data indicate that bispidine-based ligand systems are suitable starting points for constructing novel, high-denticity chelators for specific complexation of larger radiotheranostic metal ion nuclides.

Capturing Sialyl-glycan on Live Cancer Cells by Tailored Boronopeptide.

Boronic acid-containing molecules are substantially popularized in chemical biology and medicinal chemistry due to the broad spectrum of covalent conjugations as well as interaction modules offered by the versatile boron atom. Apparently, the WGA peptide (wheat germ agglutinin, 62-73), which shows a considerably low binding affinity to sialic acid, turned into a selective and >5 folds potent binder with the aid of a suitable boronic acid probe installed chemoselectively. In silico studies prompted us to install BA probes on the cysteine residue, supposedly located in close proximity to the bound sialic acid. In vitro studies revealed that the tailored boronopeptides show enhanced binding ability due to the synergistic recognition governed by selective non-covalent interactions and cis-diol boronic acid conjugation. The intense binding is observed even in 10 % serum, thus enabling profiling of sialyl-glycan on cancer cells, as compared with the widely used lectin, Sambucus nigra. The synergistic binding mode between the best boronopeptide (P3) binder and sialic acid was analyzed via 1 H and 11 B NMR.

In Vivo Microstructure Imaging in Oropharyngeal Squamous Cell Carcinoma Using the Random Walk With Barriers Model.

BACKGROUND: Apparent diffusion coefficient is not specifically sensitive to tumor microstructure and therapy-induced cellular changes. PURPOSE: To investigate time-dependent diffusion imaging with the short-time-limit random walk with barriers model (STL-RWBM) for quantifying microstructure parameters and early cancer cellular response to therapy. STUDY TYPE: Prospective. POPULATION: Twenty-seven patients (median age of 58 years and 7.4% of females) with p16+/p16- oropharyngeal/oral cavity squamous cell carcinomas (OPSCC/OCSCC) underwent MRI scans before therapy, of which 16 patients had second scans at 2 weeks of the 7-weeks chemoradiation therapy (CRT). FIELD STRENGTH/SEQUENCE: 3-T, diffusion sequence with oscillating gradient spine echo (OGSE) and pulse gradient spin echo (PGSE). ASSESSMENT: Diffusion weighted images were acquired using OGSE and PGSE. Effective diffusion times were derived for the STL-RWBM to estimate free diffusion coefficient D0 , volume-to-surface area ratio of cellular membranes V/S, and cell membrane permeability κ. Mean values of these parameters were calculated in tumor volumes. STATISTICAL TESTS: Tumor microstructure parameters were compared with clinical stages of p16+ I-II OPSCC, p16+ III OPSCC, and p16- IV OCSCC by Spearman's rank correlation and with digital pathological analysis of a resected tissue sample. Tumor microstructure parameter responses during CRT in the 16 patients were assessed by paired t-tests. A P-value of <0.05 was considered statistically significant. RESULTS: The derived effective diffusion times affected estimated values of V/S and κ by 40%. The tumor V/S values were significantly correlated with clinical stages (r = 0.47) as an increase from low to high clinical stages. The in vivo estimated cell size agreed with one from pathological analysis of a tissue sample. Early tumor cellular responses showed a significant increase in D0 (14%, P = 0.03) and non-significant increases in κ (56%, P = 0.6) and V/S (10%, P = 0.1). DATA CONCLUSION: Effective diffusion time estimation might impact microstructure parameter estimation. The tumor V/S was correlated with OPSCC/OCSCC clinical stages. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Nanozymes and carbon-dots based nanoplatforms for cancer imaging, diagnosis and therapeutics: Current trends and challenges.

Cancer patients face a significant clinical and socio-economic burden due to increased incidence, mortality, and poor survival. Factors like late diagnosis, recurrence, drug resistance, severe side effects, and poor bioavailability limit the scope of current therapies. There is a need for novel, cost-effective, and safe diagnostic methods, therapeutics to overcome recurrence and drug resistance, and drug delivery vehicles with enhanced bioavailability and less off-site toxicity. Advanced nanomaterial-based research is aiding cancer biologists by providing solutions for issues like hypoxia, tumor microenvironment, low stability, poor penetration, target non-specificity, and rapid drug clearance. Currently, nanozymes and carbon-dots are attractive due to their low cost, high catalytic activity, biocompatibility, and lower toxicity. Nanozymes and carbon-dots are increasingly used in imaging, biosensing, diagnosis, and targeted cancer therapy. Integrating these materials with advanced diagnostic tools like CT scans and MRIs can aid in clinical decision-making and enhance the effectiveness of chemotherapy, photothermal, photodynamic, and sonodynamic therapies, with minimal invasion and reduced collateral effects.

Incidental findings on staging rectal MRI: clinical significance and outcomes.

BACKGROUND: Incidental findings (IFs) are commonly seen in staging rectal magnetic resonance imaging (MRI) scans. Their prevalence and clinical significance have not been previously documented. PURPOSE: To assess the prevalence, clinical significance, and outcomes of incidental findings in MRI scans performed for the staging of rectal cancer. MATERIAL AND METHODS: A retrospective study was performed at a tertiary colorectal imaging institution. Consecutive MRI rectal staging scans with correlative pathology confirmed primary rectal cancer between March 2014 and March 2021 were identified. The respective imaging reports were reviewed for IFs, which were classified as high, moderate, and low, according to their clinical significance. Medical records were reviewed to assess the outcomes of the highly significant IFs. RESULTS: There were 266 eligible patients (97 women; mean age = 64.2 years) during the study period. A total of 120 (45%) patients did not have any IFs. A total of 238 IFs in 146 (55%) patients were found. There were 21 (9%) IFs of high clinical significance, 122 (51%) of moderate clinical significance, and 95 (40%) of low clinical significance. The prostate and uterus had the most IFs of high clinical significance, two of which were subsequently pathology confirmed as prostate adenocarcinomas. CONCLUSION: IFs were seen in more than half of the staging MRI scans in rectal cancer but less than 10% of these were of high clinical significance. The results of this study highlight the range of potential IFs and can guide future research assessing the potential impact of these IFs on patients and the healthcare system.

Hyper-Branched Gold Nanoconstructs for Photoacoustic Imaging in the Near-Infrared Optical Window.

In plasmonic nanoconstructs (NCs), fine-tuning interparticle interactions at the subnanoscale offer enhanced electromagnetic and thermal responses in the near-infrared (NIR) wavelength range. Due to tunable electromagnetic and thermal characteristics, NCs can be excellent photoacoustic (PA) imaging contrast agents. However, engineering plasmonic NCs that maximize light absorption efficiency across multiple polarization directions, i.e., exhibiting blackbody absorption behavior, remains challenging. Herein, we present the synthesis, computational simulation, and characterization of hyper-branched gold nanoconstructs (HBGNCs) as a highly efficient PA contrast agent. HBGNCs exhibit remarkable optical properties, including strong NIR absorption, high absorption efficiency across various polarization angles, and superior photostability compared to conventional standard plasmonic NC-based contrast agents such as gold nanorods and gold nanostars. In vitro and in vivo experiments confirm the suitability of HBGNCs for cancer imaging, showcasing their potential as reliable PA contrast agents and addressing the need for enhanced imaging contrast and stability in bioimaging applications.

Potential Application of the Myocardial Scintigraphy Agent [123I]BMIPP in Colon Cancer Cell Imaging.

[123I]ß-methyl-p-iodophenyl-pentadecanoic acid ([123I]BMIPP), which is used for nuclear medicine imaging of myocardial fatty acid metabolism, accumulates in cancer cells. However, the mechanism of accumulation remains unknown. Therefore, this study aimed to elucidate the accumulation and accumulation mechanism of [123I]BMIPP in cancer cells. We compared the accumulation of [123I]BMIPP in cancer cells with that of [18F]FDG and found that [123I]BMIPP was a much higher accumulation than [18F]FDG. The accumulation of [123I]BMIPP was evaluated in the presence of sulfosuccinimidyl oleate (SSO), a CD36 inhibitor, and lipofermata, a fatty acid transport protein (FATP) inhibitor, under low-temperature conditions and in the presence of etomoxir, a carnitine palmitoyl transferase I (CPT1) inhibitor. The results showed that [123I]BMIPP accumulation was decreased in the presence of SSO and lipofermata in H441, LS180, and DLD-1 cells, suggesting that FATPs and CD36 are involved in [123I]BMIPP uptake in cancer cells. [123I]BMIPP accumulation in all cancer cell lines was significantly decreased at 4 °C compared to that at 37 °C and increased in the presence of etomoxir in all cancer cell lines, suggesting that the accumulation of [123I]BMIPP in cancer cells is metabolically dependent. In a biological distribution study conducted using tumor-bearing mice transplanted with LS180 cells, [123I]BMIPP highly accumulated in not only LS180 cells but also normal tissues and organs (including blood and muscle). The tumor-to-intestine or large intestine ratios of [123I]BMIPP were similar to those of [18F]FDG, and the tumor-to-large-intestine ratios exceeded 1.0 during 30 min after [123I]BMIPP administration in the in vivo study. [123I]BMIPP is taken up by cancer cells via CD36 and FATP and incorporated into mitochondria via CPT1. Therefore, [123I]BMIPP may be useful for imaging cancers with activated fatty acid metabolism, such as colon cancer. However, the development of novel imaging radiotracers based on the chemical structure analog of [123I]BMIPP is needed.

New opportunities for RGD-engineered metal nanoparticles in cancer.

The advent of nanotechnology has opened new possibilities for bioimaging. Metal nanoparticles (such as gold, silver, iron, copper, etc.) hold tremendous potential and offer enormous opportunities for imaging and diagnostics due to their broad optical characteristics, ease of manufacturing technique, and simple surface modification. The arginine-glycine-aspartate (RGD) peptide is a three-amino acid sequence that seems to have a considerably greater ability to adhere to integrin adhesion molecules that exclusively express on tumour cells. RGD peptides act as the efficient tailoring ligand with a variety of benefits including non-toxicity, greater precision, rapid clearance, etc. This review focuses on the possibility of non-invasive cancer imaging using metal nanoparticles with RGD assistance.

Probing lipids relaxation times in breast cancer using magnetic resonance spectroscopic fingerprinting.

OBJECTIVES: To investigate the clinical relevance of the relaxation times of lipids within breast cancer and normal fibroglandular tissue in vivo, using magnetic resonance spectroscopic fingerprinting (MRSF). METHODS: Twelve patients with biopsy-confirmed breast cancer and 14 healthy controls were prospectively scanned at 3 T using a protocol consisting of diffusion tensor imaging (DTI), MRSF, and dynamic contrast-enhanced (DCE) MRI. Single-voxel MRSF data was recorded from the tumor (patients) - identified using DTI - or normal fibroglandular tissue (controls), in under 20 s. MRSF data was analyzed using in-house software. Linear mixed model analysis was used to compare the relaxation times of lipids in breast cancer VOIs vs. normal fibroglandular tissue. RESULTS: Seven distinguished lipid metabolite peaks were identified and their relaxation times were recorded. Of them, several exhibited statistically significant changes between controls and patients, with strong significance (p < 10-3) recorded for several of the lipid resonances at 1.3 ppm (T1 = 355 ± 17 ms vs. 389 ± 27 ms), 4.1 ppm (T1 = 255 ± 86 ms vs. 127 ± 33 ms), 5.22 ppm (T1 = 724 ± 81 ms vs. 516 ± 62 ms), and 5.31 ppm (T2 = 56 ± 5 ms vs. 44 ± 3.5 ms, respectively). CONCLUSIONS: The application of MRSF to breast cancer imaging is feasible and achievable in clinically relevant scan time. Further studies are required to verify and comprehend the underling biological mechanism behind the differences in lipid relaxation times in cancer and normal fibroglandular tissue. KEY POINTS: •The relaxation times of lipids in breast tissue are potential markers for quantitative characterization of the normal fibroglandular tissue and cancer. •Lipid relaxation times can be acquired rapidly in a clinically relevant manner using a single-voxel technique, termed MRSF. •Relaxation times of T1 at 1.3 ppm, 4.1 ppm, and 5.22 ppm, as well as of T2 at 5.31 ppm, were significantly different between measurements within breast cancer and the normal fibroglandular tissue.

Introduction to the COG Diagnostic Imaging Committee/SPR Oncology Committee White Papers: Rationale and methods.

Pediatric cancer is a rare disease. Because of this, many sites do not have experience providing imaging for specific tumor types. The Children's Oncology Group Diagnostic Imaging Committee and the Society for Pediatric Radiology Oncology Committee are comprised of radiologists with expertise in pediatric cancer imaging. Recently, this group endeavored to create a series of 23 White Papers designed to provide evidence-based imaging recommendations and minimum achievable imaging protocols. The purpose of this manuscript is to describe the methods employed in authoring the White Paper series.

Ferumoxytol-Enhanced MRI in Children and Young Adults: State of the Art.

Ferumoxytol is an ultrasmall iron oxide nanoparticle that was originally approved by the FDA in 2009 for IV treatment of iron deficiency in adults with chronic kidney disease. Subsequently, its off-label use as an MRI contrast agent increased in clinical practice, particularly in pediatric patients in North America. Unlike conventional MRI contrast agents that are based on the rare earth metal gadolinium (gadolinium-based contrast agents), ferumoxytol is biodegradable and carries no potential risk of nephrogenic systemic fibrosis. At FDA-approved doses, ferumoxytol shows no long-term tissue retention in patients with intact iron metabolism. Ferumoxytol provides unique MRI properties, including long-lasting vascular retention (facilitating high-quality vascular imaging) and retention in reticuloendothelial system tissues, thereby supporting a variety of applications beyond those possible with gadolinium-based contrast agents (GBCAs). This Clinical Perspective describes clinical and early translational applications of ferumoxytol-enhanced MRI in children and young adults through off-label use in a variety of settings, including vascular, cardiac, and cancer imaging, drawing on the institutional experience of the authors. In addition, we describe current advances in pre-clinical and clinical research using ferumoxytol in cellular and molecular imaging as well as the use of ferumoxytol as a novel potential cancer therapeutic agent.

Synthesis and Biological Evaluation of New Fluorescent Probe BPN-01: A Model Molecule for Fluorescence Image-guided Surgery.

Fluorescence image-guided surgery (FIGS) can serve as a tool to achieve successful resection of tumour tissues during surgery, serving as a surgical navigator for surgeons. FIGS relies on the use of fluorescent molecules that can specifically interact with cancer cells. In this work, we developed a new model of fluorescent probe based on benzothiazole-phenylamide moiety featuring the visible fluorophore nitrobenzoxadiazole (NBD), namely BPN-01. This compound was designed and synthesised for potential applications in the tissue biopsy examination and ex-vivo imaging during FIGS of solid cancers. The probe BPN-01 exhibited favourable spectroscopic properties, particularly in nonpolar and alkaline solvents. Moreover, in vitro fluorescence imaging revealed that the probe appeared to recognise and be internalised in the prostate (DU-145) and melanoma (B16-F10) cancer cells, but not in the normal cells (myoblast C2C12). The cytotoxicity studies revealed that probe BPN-01 was not toxic to the B16 cells, suggesting excellent biocompatibility. Furthermore, the computational analysis showed that the calculated binding affinity of the probe to both translocator protein 18 kDa (TSPO) and human epidermal growth factor receptor 2 (HER2) was considerably high. Hence, probe BPN-01 displays promising properties and may be valuable for visualising cancer cells in vitro. Furthermore, ligand 5 can potentially be labelled with NIR fluorophore and radionuclide, and serves as a dual imaging agent for in vivo applications.

Metric Learning in Histopathological Image Classification: Opening the Black Box.

The application of machine learning techniques to histopathology images enables advances in the field, providing valuable tools that can speed up and facilitate the diagnosis process. The classification of these images is a relevant aid for physicians who have to process a large number of images in long and repetitive tasks. This work proposes the adoption of metric learning that, beyond the task of classifying images, can provide additional information able to support the decision of the classification system. In particular, triplet networks have been employed to create a representation in the embedding space that gathers together images of the same class while tending to separate images with different labels. The obtained representation shows an evident separation of the classes with the possibility of evaluating the similarity and the dissimilarity among input images according to distance criteria. The model has been tested on the BreakHis dataset, a reference and largely used dataset that collects breast cancer images with eight pathology labels and four magnification levels. Our proposed classification model achieves relevant performance on the patient level, with the advantage of providing interpretable information for the obtained results, which represent a specific feature missed by the all the recent methodologies proposed for the same purpose.

Evaluation of the Resolution in Inverse Scattering of Dielectric Cylinders for Medical Applications.

The inverse scattering problem has numerous significant applications, including in geophysical explorations, medical imaging, and radar imaging. To achieve better performance of the imaging system, theoretical knowledge of the resolution of the algorithm is required for most of these applications. However, analytical investigations about the resolution presently feel inadequate. In order to estimate the achievable resolution, we address the point spread function (PSF) evaluation of the scattered field for a single frequency and the multi-view case both for the near and the far fields and the scalar case when the angular domain of the incident field and observation ranges is a round angle. Instead of the common free space condition, an inhomogeneous background medium, consisting of a homogeneous dielectric cylinder with a circular cross-section in free space, is assumed. In addition, since the exact evaluation of the PSF can only be accomplished numerically, an analytical approximation of the resolution is also considered. For the sake of its comparison, the truncated singular value decomposition (TSVD) algorithm can be used to implement the exact PSF. We show how the behavior of the singular values and the resolution change by varying the permittivity of the background medium. The usefulness of the theoretical discussion is demonstrated in localizing point-like scatterers within a dielectric cylinder, so mimicking a scenario that may occur in breast cancer imaging. Numerical results are provided to validate the analytical investigations.

Development and Characterization of 99mTc-scFvD2B as a Potential Radiopharmaceutical for SPECT Imaging of Prostate Cancer.

Previously, we demonstrated that the 177Lu-labeled single-chain variable fragment of an anti-prostate-specific membrane antigen (PSMA) IgG D2B antibody (scFvD2B) showed higher prostate cancer (PCa) cell uptake and tumor radiation doses compared to 177Lu-labeled Glu-ureide-based PSMA inhibitory peptides. To obtain a 99mTc-/177Lu-scFvD2B theranostic pair, this research aimed to synthesize and biochemically characterize a novel 99mTc-scFvD2B radiotracer. The scFvD2B-Tag and scFvD2B antibody fragments were produced and purified. Then, two HYNIC derivatives, HYNIC-Gly-Gly-Cys-NH2 (HYNIC-GGC) and succinimidyl-HYNIC (S-HYNIC), were used to conjugate the scFvD2B-Tag and scFvD2B isoforms, respectively. Subsequently, chemical characterization, immunoreactivity tests (affinity and specificity), radiochemical purity tests, stability tests in human serum, cellular uptake and internalization in LNCaP(+), PC3-PIP(++) or PC3(-) PCa cells of the resulting unlabeled HYNIC-scFvD2B conjugates (HscFv) and 99mTc-HscFv agents were performed. The results showed that incorporating HYNIC as a chelator did not affect the affinity, specificity or stability of scFvD2B. After purification, the radiochemical purity of 99mTc-HscFv radiotracers was greater than 95%. A two-sample t-test of 99mTc-HscFv1 and 99mTc-HscFv1 uptake in PC3-PIP vs. PC3 showed a p-value < 0.001, indicating that the PSMA receptor interaction of 99mTc-HscFv agents was statistically significantly higher in PSMA-positive cells than in the negative controls. In conclusion, the results of this research warrant further preclinical studies to determine whether the in vivo pharmacokinetics and tumor uptake of 99mTc-HscFv still offer sufficient advantages over HYNIC-conjugated peptides to be considered for SPECT/PSMA imaging.

TCGA RNA-Seq and Tumor-Infiltrating Lymphocyte Imaging Data Reveal Cold Tumor Signatures of Invasive Ductal Carcinomas and Estrogen Receptor-Positive Human Breast Tumors.

Comparative studies of immune-active hot and immune-deserted cold tumors are critical for identifying therapeutic targets and strategies to improve immunotherapy outcomes in cancer patients. Tumors with high tumor-infiltrating lymphocytes (TILs) are likely to respond to immunotherapy. We used the human breast cancer RNA-seq data from the cancer genome atlas (TCGA) and classified them into hot and cold tumors based on their lymphocyte infiltration scores. We compared the immune profiles of hot and cold tumors, their corresponding normal tissue adjacent to the tumor (NAT), and normal breast tissues from healthy individuals from the Genotype-Tissue Expression (GTEx) database. Cold tumors showed a significantly lower effector T cells, lower levels of antigen presentation, higher pro-tumorigenic M2 macrophages, and higher expression of extracellular matrix (ECM) stiffness-associated genes. Hot/cold dichotomy was further tested using TIL maps and H&E whole-slide pathology images from the cancer imaging archive (TCIA). Analysis of both datasets revealed that infiltrating ductal carcinoma and estrogen receptor ER-positive tumors were significantly associated with cold features. However, only TIL map analysis indicated lobular carcinomas as cold tumors and triple-negative breast cancers (TNBC) as hot tumors. Thus, RNA-seq data may be clinically relevant to tumor immune signatures when the results are supported by pathological evidence.

CT features of subcutaneous, intermuscular, and intramuscular mast cell tumors in dogs.

Surgical removal is the treatment of choice for subcutaneous (SC), intermuscular (InterM), and intramuscular (IntraM) mast cell tumors (MCTs). Advanced imaging (CT or MRI) is frequently used for presurgical planning, but InterM and IntraM MCTs can be difficult to identify and delineate on CT. Aims of the current retrospective, diagnostic accuracy, observer agreement study were to describe the imaging features of SC, InterM, and IntraM MCTs on CT and to assess the limitation of CT to identify the full local extent of the MCT. Inclusion criteria for the study were dogs with a cytologically or histologically diagnosed MCTs determined to be SC, InterM, or IntraM MCT based on histology and/or a CT scan performed in the gross disease setting. Two board-certified veterinary radiologists reviewed the CT images and recorded location, contrast enhancement pattern, and delineation between the normal and abnormal tissue. Sensitivity and specificity of CT for determining location (SC/InterM versus IntraM) was 85.71% and 55.56%, respectively, when compared to consensus location based on surgical pathology report/CT/MRI review. There was a low inter-rater agreement for delineation (kappa: 0.150 (-0.070 to 0.370) and measurement had a low/moderate correlation (rho: 0.4667 to 0.5792). Upon review by a surgical oncologist, CT findings were deemed insufficient for curative surgical planning in 13 of 16 due to inadequate definition of tumor depth, compartment boundary (fascial plane) or MCT margins. The use of CT for presurgical planning of SC/InterM/IntraM MCT dogs has limitations, especially when differentiating MCT from the adjacent muscle.

Recent progress in the imaging of c-Met aberrant cancers with positron emission tomography.

Tyrosine-protein kinase Met-also known as c-Met or HGFR-is a membrane receptor protein with associated tyrosine kinase activity physiologically stimulated by its natural ligand, the hepatocyte growth factor (HGF), and is involved in different ways in cancer progression and tumourigenesis. Targeting c-Met with pharmaceuticals has been preclinically proved to have significant benefits for cancer treatment. Recently, evaluating the protein status during and before c-Met targeted therapy has been shown of relevant importance by different studies, demonstrating that there is a correlation between the status (e.g., aberrant activation and overexpression) of the HGFR with therapy response and clinical prognosis. Currently, clinical imaging based on positron emission tomography (PET) appears as one of the most promising tools for the in vivo real-time scanning of irregular alterations of the tyrosine-protein kinase Met and for the diagnosis of c-Met related cancers. In this study, we review the recent progress in the imaging of c-Met aberrant cancers with PET. Particular attention is directed on the development of PET probes with a range of different sizes (HGF, antibodies, anticalines, peptides, and small molecules), and radiolabeled with different radionuclides. The goal of this review is to report all the preclinical imaging studies based on PET imaging reported until now for in vivo diagnosis of c-Met in oncology to support the design of novel and more effective PET probes for in vivo evaluation of c-Met.