Tumor Imaging Research Articles

68Ga-OncoFAP microPET/CT imaging in different breast cancer mouse models

BackgroundBreast cancer (BC) is currently the most common malignancy worldwide and the leading cause of cancer-related death in women. Positron emission tomography/computed tomography (PET/CT) with fluorine-18-2-fluoro-2-deoxy-glucose (18F-FDG-PET) plays an important role in staging breast cancer, and now many promising tracers for tumor imaging are striving for superior breast cancer detection and monitoring. Some studies have reported better results regarding the diagnostic and therapeutic value of FAP ligands, especially in the diagnostic evaluation of primary BC. MethodsIn this study, we have successfully radiolabeled the 68Ga-OncoFAP, which is FAP (Fibroblast activation protein) targeting tracer, and tested the imaging efficacy in both subcutaneous ER-positive MCF-7 breast cancer tumors models and orthotopic triple negative MDA-MB-231 breast cancer tumor models. ResultsMCF-7 subcutaneous tumors and MDA-MB-231 orthotopic tumors exhibited a high uptake of 68Ga-OncoFAP, which correlated with the corresponding pathological results. Between 30 and 100 min post injection, the tumor-to-background ratio (TBR) of MDA-MB-231 orthotopic tumors gradually decreased, but to a limited extent, all less than 10%. 68Ga-labeled OncoFAP could be applied for noninvasive imaging of breast cancer, and we could observe the metabolism of the probe by the MicroPET imaging. Conclusions68Ga-OncoFAP could selectively image fibroblast activation protein in mice models and is very promising for the diagnosis of different histological and molecular subtypes of breast cancer.

Portal Venous Tumor Thrombosis and Visceral Organ Metastasis without Skeletal Involvement in mCRPC: Adverse Prognostic Indicators on Dual Tracer PET/CT and Clinical Outcome after 177Lu-PSMA-617 PRLT and Cabazitaxel Therapy

AbstractProstate cancer involving visceral organs are occurrences in the later disease course, usually following regional nodal and skeletal involvement, and are refractory to conventional treatment. A 61-year-old male patient presented with locally advanced disease at presentation, which progressed on androgen deprivation therapy and systemic therapy with involvement of the visceral organs (lungs and liver). Portal venous tumor thrombosis involving the right and main branch was also observed on contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI), which showed intense uptake on 68Ga-labeled prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) and 18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT). Post-177Lu-PSMA-617 radioligand therapy (PRLT) showed mixed response on tumor marker and imaging analysis with survival of 6 months after 177Lu-PSMA radioligand therapy. The high Gleason score, visceral organ metastasis, and increased metabolic activity on FDG were the adverse prognostic factors in the described patient.

Comparison of Clinical Outcomes between Microscopic and Endoscopic Transsphenoidal Pituitary Tumor Resection

Abstract Objectives In recent years, the transnasal endoscopic method for transsphenoidal pituitary tumor resection (eTSR), alongside the conventional sublabial microscopic transsphenoidal resection (mTSR) method, has gained popularity due to advancements in imaging and instrumentation. The current study sought to elucidate whether the trend toward eTSR was associated with changes in clinical outcomes at a single institution's multidisciplinary pituitary surgery program. Setting and Participants The Virginia Commonwealth University (VCU) Brain Tumor Database was queried for patients who underwent either transnasal or sublabial pituitary tumor resection of pituitary tumors between 2009 and 2021. Design Clinical outcomes were compared between the two groups. Main Outcome Measures Surgical outcomes like estimated blood loss (EBL), cerebrospinal fluid (CSF) leak rates, hospital length of stay (LOS), and extent of resection were studied. Results A total of 93 patients (57 mTSR, 36 eTSR) underwent review, revealing that mTSR was associated with a higher average intraoperative blood loss (310.5 ± 48.6 mL) than eTSR (160.0 ± 30.7 mL; p = 0.012). eTSR demonstrated an elevated intraoperative CSF leak incidence (36.1 vs. 15.8%; p = 0.043), but no difference in postoperative CSF leak requiring intervention. Hospital LOS and extent of resection showed no significant differences between the approaches. Conclusion This single-institution, retrospective study suggests that, in experienced hands, both eTSR and mTSR approaches are effective with comparable risk profiles. The approach may be best determined by the surgical team's evaluation of the tumor's imaging features, paying attention to the patient's preoperative hematologic status due to the greater propensity for blood loss with the microscopic approach.

Zwitterionic nanoparticles from indocyanine green dimerization for imaging-guided cancer phototherapy

Indocyanine green (ICG), the only near-infrared (NIR) dye approved for clinical use, has received increasing attention as a theranostic agent wherein diagnosis (fluorescence) is combined with therapy (phototherapy), but suffers rapid hepatic clearance, poor photostability, and limited accumulation at tumor sites. Here we report that dimerized ICG can self-assemble to form zwitterionic nanoparticles (ZN-dICG), which generate fluorescence self-quenching but exhibit superior photothermal and photodynamic properties over ICG. The zwitterionic moieties confer ZN-dICG an ultralow critical micelle concentration and high colloidal stability with low non-specific binding in vivo. In addition, ZN-dICG can respond to the over-generated reactive oxygen species (ROSs) and dissociate to restore NIR fluorescence of ICG, amplifying the sensitivity via albumin binding for low-background imaging of tumors. Following systemic administration, ZN-dICG accumulated in tumors of xenograft-bearing mice for imaging primary and metastatic tumors, and induced tumor ablation under laser irradiation. The discovery of ZN-dICG would contribute to the design of translational phototheranostic platform with high biocompatibility. Statement of significanceIndocyanine green (ICG) has been extensively studied as a phototheranostic agent that combines imaging with phototherapies, but it suffers from rapid hepatic clearance, poor photostability, and limited accumulation at tumor sites. Here, we report a strategy to construct ICG dimers (ICG-tk-ICG) by conjugating two ICG molecules via a thioketal bond, which can self-assemble into zwitterionic nanoparticles (ZN-dICG) at ultralow critical micelle concentrations, exhibiting superior photothermal and photodynamic properties over ICG. ZN-dICG responds to the over-generated ROS in tumors and dissociates to restore the NIR fluorescence of ICG, enhancing the sensitivity via albumin binding for low-background imaging of tumors. This study offers a supramolecular strategy that may potentiate the clinical translation of ICG in imaging-guided cancer phototherapy.

Prediction of Motor Recovery Using Diffusion Tensor Imaging and Regional Cerebral Blood Flow in Postoperative Brain Tumors.

To determine whether diffusion tensor image (DTI) parameters and regional cerebral blood flow (rCBF) serve to preoperatively predict postoperative motor outcomes in patients with brain tumors. We included 81 patients with brain tumors who underwent surgical treatment. Motor function was assessed using the manual muscle test in the upper and lower limbs at admission and discharge. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and their ratios (rFA, rMD, rAD, and rRD) were measured at the corona radiata, internal capsule, and cerebral peduncle of the corticospinal tract (CST). In addition, DTI and single photon emission computed tomography (SPECT) were synthesized to measure rCBF at the CST. Both DTI parameters and rCBF at the CST in the preoperative motor weakness group significantly differed from those of the preoperative normal function group. rFA at the cerebral peduncle and the internal capsule was considerably higher in those showing postoperative motor recovery than in those postoperative unchanged or with deteriorated motor function (P < 0.05). Moreover, there was significantly lower rMD and rRD at the internal capsule in the motor recovery group (P < 0.05, P < 0.01).Furthermore, rCBF was higher at all the cerebral peduncle, internal capsule, and corona radiate in the motor recovery group than in the unchanged and deteriorated motor function group (P < 0.05, P < 0.01, P < 0.01). The analysis of DTI parameters and rCBF is useful in predicting postoperative motor outcomes in patients with brain tumors.

Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR).

The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls. A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in 'group consensus', 'group agreement', or 'lack of agreement'. The three sections contain 24 statements with comments. Group consensus was reached in 95.8% and group agreement in 4.2%. For whole-body staging, pulmonary MDCT should be performed in all high-grade sarcomas. Whole-body MRI is preferred for staging bone metastasis, with [18F]FDG-PET/CT as an alternative modality in PET-avid tumors. Patients with alveolar soft part sarcoma, clear cell sarcoma, and angiosarcoma should be screened for brain metastases. Special algorithms are recommended for entities such as rhabdomyosarcoma, extraskeletal Ewing sarcoma, myxoid liposarcoma, and neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors. Satisfaction of search should be avoided in potential multiplicity. Standardized whole-body staging includes pulmonary MDCT in all high-grade sarcomas; entity-dependent modifications and specific algorithms are recommended for sarcomas and non-malignant soft tissue tumors. These updated ESSR soft tissue tumor imaging guidelines aim to provide support in decision-making, helping to avoid common pitfalls, by providing general and entity-specific algorithms, techniques, and reporting recommendations for whole-body staging in sarcoma and non-malignant soft tissue tumors. An early, accurate, diagnosis is crucial for the prognosis of patients with soft tissue tumors. These updated guidelines provide best practice expert consensus for standardized imaging algorithms, techniques, and reporting. Standardization can improve the comparability examinations and provide databases for large data analysis.

Contrast-enhanced photon-counting micro-CT of tumor xenograft models

Objective. Photon-counting micro-computed tomography (micro-CT) is a major advance in small animal preclinical imaging. Small molecule- and nanoparticle-based contrast agents have been widely used to enable the differentiation of liver tumors from surrounding tissues using photon-counting micro-CT. However, there is a notable gap in the application of these market-available agents to the imaging of breast and ovarian tumors using photon-counting micro-CT. Herein, we have used photon-counting micro-CT to determine the effectiveness of these contrast agents in differentiating ovarian and breast tumor xenografts in live, intact mice. Approach. Nude mice carrying different types of breast and ovarian tumor xenografts (AU565, MDA-MB-231 and SKOV-3 human cancer cells) were injected with ISOVUE-370 (a small molecule-based agent) or Exitron Nano 12000 (a nanoparticle-based agent) and subjected to photon-counting micro-CT. To improve tumor visualization using photon-counting micro-CT, we developed a novel color visualization method, which changes color tones to highlight contrast media distribution, offering a robust alternative to traditional material decomposition methods with less computational demand. Main results. Our in vivo experiments confirm the effectiveness of this color visualization approach, showing distinct enhancement characteristics for each contrast agent. Qualitative and quantitative analyses suggest that Exitron Nano 12000 provides superior vasculature enhancement and better quantitative consistency across scans, while ISOVUE-370 delivers a more comprehensive tumor enhancement but with significant variance between scans due to its short blood half-time. Further, a paired t-test on mean and standard deviation values within tumor volumes showed significant differences between the AU565 and SKOV-3 tumor models with the nanoparticle-based contrast agent (p-values < 0.02), attributable to their distinct vascularity, as confirmed by immunohistochemical analysis. Significance. These findings underscore the utility of photon-counting micro-CT in non-invasively assessing the morphology and anatomy of different tumor xenografts, which is crucial for tumor characterization and longitudinal monitoring of tumor progression and response to treatments.

Metal-Coordinated Polydopamine Structures for Tumor Imaging and Therapy.

Meticulously engineered nanomaterials achieve significant advances in the diagnosis and therapy of solid tumors by improving tumor delivery efficiency; and thereby, enhancing imaging and therapeutic efficacy. Currently, polydopamine (PDA) attracts widespread attention because of its biocompatibility, simplicity of preparation, abundant surface groups, and high photothermal conversion efficiency, which can be applied in drug delivery, photothermal therapy, theranostics, and other nanomedicine fields. Inspired by PDA structures that are rich in catechol and amino functional groups that can coordinate with various metal ions, which have charming qualities and characteristics, metal-coordinated PDA structures are exploited for tumor theranostics, but are not thoroughly summarized. Herein, this review summarizes the recent progress in the fabrication of metal-coordinated PDA structures and their availabilities in tumor imaging and therapy, with further in-depth discussion of the challenges and future perspectives of metal-coordinated PDA structures, with the aim that this systematic review can promote interdisciplinary intersections and provide inspiration for the further growth and clinical translation of PDA materials.

Recent Advances in Pretargeted Strategy for Cancer Theranostics.

In nuclear medicine, theranostic probes that combine nuclear imaging capabilities with therapeutic functions have shown promise for the diagnosis and treatment of cancers. Nevertheless, the development of theranostic probes may be constrained by two principal factors: (1) the discrepancy between the slow accumulation time of the probes in the tumours and the short-lived radionuclides, and (2) the suboptimal imaging/treatment effect and high radioactive toxicity caused by long-lived radionuclides. In recent years, pretargeted strategy has been proposed as a potential solution to solve these problems. In the pretargeted strategy, two components consisting of a tumour-targeting vector (e.g., antibody) and a radionuclide are injected separately, which can then couple in the tumour tissues to trap radionuclides for nuclear imaging and/or therapy. This two-step process allows for the independent optimization of the pharmacokinetics of them in vivo, benefiting to improve nuclear imaging and/or therapy of tumours in vivo. In this concept, we will discuss the principle of the pretargeted strategy, with a focus on the discussion of different tumour-targeting vectors, including antibody-mediated delivery, nanoparticle-mediated delivery, metabolic glycan labeling-mediated accumulation, and enzyme-triggered in situ self-assembly-mediated retention. Finally, we will discuss the current challenges and perspectives on their applications for cancer theranostics in clinics.

A Multi-Center, Multi-Parametric MRI Dataset of Primary and Secondary Brain Tumors

Brain metastases (BMs) and high-grade gliomas (HGGs) are the most common and aggressive types of malignant brain tumors in adults, with often poor prognosis and short survival. As their clinical symptoms and image appearances on conventional magnetic resonance imaging (MRI) can be astonishingly similar, their accurate differentiation based solely on clinical and radiological information can be very challenging, particularly for “cancer of unknown primary”, where no systemic malignancy is known or found. Non-invasive multiparametric MRI and radiomics offer the potential to identify these distinct biological properties, aiding in the characterization and differentiation of HGGs and BMs. However, there is a scarcity of publicly available multi-origin brain tumor imaging data for tumor characterization. In this paper, we introduce a multi-center, multi-origin brain tumor MRI (MOTUM) imaging dataset obtained from 67 patients: 29 with high-grade gliomas, 20 with lung metastases, 10 with breast metastases, 2 with gastric metastasis, 4 with ovarian metastasis, and 2 with melanoma metastasis. This dataset includes anonymized DICOM files alongside processed FLAIR, T1-weighted, contrast-enhanced T1-weighted, T2-weighted sequences images, segmentation masks of two tumor regions, and clinical data. Our data-sharing initiative is to support the benchmarking of automated tumor segmentation, multi-modal machine learning, and disease differentiation of multi-origin brain tumors in a multi-center setting.

Quinazoline-2,4(1H,3H)-dione Scaffold for development of a novel PARP-targeting PET probe for tumor imaging.

Overexpression of Poly (ADP-ribose) polymerase (PARP) is associated with many diseases such as oncological diseases. Several PARP-targeting radiotracers have been developed to detect tumor in recent years. Two 18F labelled probes based on Olaparib and Rucaparib molecular scaffolds have been evaluated in clinical trials, but their slow hepatic clearance hinders their tumor imaging performance. Although a number of positron emission tomography (PET) probes with lower liver uptake have been designed, the tumor to background ratios remains to be low. Therefore, we designed a probe with low lipid-water partition coefficient to solve this problem. A pyridine-containing quinazoline-2,4(1H,3H)-dione PARP-targeting group was rationally designed and used to conjugate with the chelator 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) to prepare the lead compound named as SMIC-2001 for radiolabeling. In vitro experiments, the lipid-water partition coefficient, stability, binding affinity, and cellular uptake of [68Ga]Ga-SMIC-2001 were determined. In vivo experiments, the U87MG xenograft models were used to evaluate its tumor imaging properties. [68Ga]Ga-SMIC-2001 showed a low Log D7.4 (-3.82 ± 0.06) and high affinity for PARP-1 (48.13 nM). In vivo study revealed that it exhibited a high tumor-to-background contrast in the U87MG xenograft models and mainly renal clearance. And the ratios of tumor to main organs were high except for the kidney (e.g. tumor to liver ratio reached 2.20 ± 0.51) at 60min p.i. In summary, pyridine-containing quinazoline-2,4(1H,3H)-dione is a novel PARP-targeting molecular scaffold for imaging probe development, and [68Ga]Ga-SMIC-2001 is a highly promising PET probe capable of imaging tumors with PARP overexpression.

Far-Red Aggregation-Induced Emission Hydrogel-Reinforced Tissue Clearing for 3D Vasculature Imaging of Whole Lung and Whole Tumor.

Understanding the vascular formation and distribution in metastatic lung tumors is a significant challenge due to autofluorescence, antibody/dye diffusion in dense tumor, and fluorophore stability when exposed to solvent-based clearing agents. Here, an approach is presented that redefines 3D vasculature imaging within metastatic tumor, peritumoral lung tissue, and normal lung. Specifically, a far-red aggregation-induced emission nanoparticle with surface amino groups (termed as TSCN nanoparticle, TSCNNP) is designed for in situ formation of hydrogel (TSCNNP@Gel) inside vasculatures to provide structural support and enhance the fluorescence in solvent-based tissue clearing method. Using this TSCNNP@Gel-reinforced tissue clearing imaging approach, the critical challenges are successfully overcome and comprehensive visualization of the whole pulmonary vasculature up to 2µm resolution is enabled, including its detailed examination in metastatic tumors. Importantly, features of tumor-associated vasculature in 3D panoramic views are unveiled, providing the potential to determine tumor stages, predict tumor progression, and facilitate the histopathological diagnosis of various tumor types.

Near-infrared II fluorescence-guided glioblastoma surgery targeting monocarboxylate transporter 4 combined with photothermal therapy

Surgery is crucial for glioma treatment, but achieving complete tumour removal remains challenging. We evaluated the effectiveness of a probe targeting monocarboxylate transporter 4 (MCT4) in recognising gliomas, and of near-infrared window II (NIR-II) fluorescent molecular imaging and photothermal therapy as treatment strategies. We combined an MCT4-specific monoclonal antibody with indocyanine green to create the probe. An orthotopic mouse model and a transwell model were used to evaluate its ability to guide tumour resection using NIR-II fluorescence and to penetrate the blood-brain barrier (BBB), respectively. A subcutaneous tumour model was established to confirm photothermal therapy efficacy. Probe specificity was assessed in brain tissue from mice and humans. Finally, probe effectiveness in photothermal therapy was investigated. MCT4 was differentially expressed in tumour and normal brain tissue. The designed probe exhibited precise tumour targeting. Tumour imaging was precise, with a signal-to-background (SBR) ratio of 2.8. Residual tumour cells were absent from brain tissue postoperatively (SBR: 6.3). The probe exhibited robust penetration of the BBB. Moreover, the probe increased the tumour temperature to 50°C within 5min of laser excitation. Photothermal therapy significantly reduced tumour volume and extended survival time in mice without damage to vital organs. These findings highlight the potential efficacy of our probe for fluorescence-guided surgery and therapeutic interventions. Jilin Province Department of Science and Technology (20200403079SF), Department of Finance (2021SCZ06) and Development and Reform Commission (20200601002JC); National Natural Science Foundation of China (92059207, 92359301, 62027901, 81930053, 81227901, U21A20386); and CAS Youth Interdisciplinary Team (JCTD-2021-08).

Melanoma progression and prognostic models drawn from single-cell, spatial maps of benign and malignant tumors.

Melanoma clinical outcomes emerge from incompletely understood genetic mechanisms operating within the tumor and its microenvironment. Here, we used single-cell RNA-based spatial molecular imaging (RNA-SMI) in patient-derived archival tumors to reveal clinically relevant markers of malignancy progression and prognosis. We examined spatial gene expression of 203,472 cells inside benign and malignant melanocytic neoplasms, including melanocytic nevi and primary invasive and metastatic melanomas. Algorithmic cell clustering paired with intratumoral comparative two-dimensional analyses visualized synergistic, spatial gene signatures linking cellular proliferation, metabolism, and malignancy, validated by protein expression. Metastatic niches included up-regulation of CDK2 and FABP5, which independently predicted poor clinical outcome in 473 patients with melanoma via Cox regression analysis. More generally, our work demonstrates a framework for applying single-cell RNA-SMI technology toward identifying gene regulatory landscapes pertinent to cancer progression and patient survival.

Development and validation of a HPLC method for the determination of chemical and radiochemical purity of O-(2-[18F]fluoroethyl-l-tyrosine ([18F]FET)), a PET radiotracer for the imaging of brain tumor

A novel HPLC method was developed and validated to determine radiochemical identity, radiochemical purity and chemical purity for the analysis of O-(2-[18F]fluoroethyl-l-tyrosine ([18F]FET). In this method, an analytical Phenomenex Gemini C18 column was used with an isocratic eluent of 7 % ethanol and 93 % 50 mM potassium phosphate buffer (pH = 6.9). The flow rate was 1.0 mL/min and the injection volume was 10 μL. A photo-diode array detector set at 220 nm was used for UV mass detection and a single channel, high sensitivity radiation detector was used. The method validation assays including specificity, linearity, precision, accuracy, and robustness were evaluated. Results show that the method was suitable for qualitative and quantitative determination of radiochemical and chemical purity of [18F]FET. This system has been routinely used for the analysis of more than 120 batches of [18F]FET with radiochemical yield 23.7 ± 6 % (no decay corrected) and molar activity 593 ± 284 GBq/μmole in our facility to support human use.

68Ga]Ga-labeled FAPI Conjugated with Gly-Pro Sequence for PET Imaging of Malignant Tumors.

To improve tumor uptake and prolong tumor retention, a novel fibroblast activation protein (FAP) ligand based on a quinoline-based FAP inhibitor (FAPI) conjugated with the Gly-Pro sequence and 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA) was radiolabeled with [68Ga]GaCl3 ([68Ga]Ga-DOTA-GPFAPI-04). Due to the tumor heterogeneity, this study aimed to further validate the preclinical value of [68Ga]Ga-DOTA-GPFAPI-04 PET imaging in tumor mice models with different FAP expression levels. [68Ga]Ga-DOTA-GPFAPI-04 was synthesized and its partition coefficient was measured. The stability of [68Ga]Ga-DOTA-GPFAPI-04 was tested in phosphate-buffered saline (PBS, pH 7.4) and fetal bovine serum (FBS). Small animal PET and semi-quantitative studies were conducted in Panc-1 and A549 xenograft tumor mice models compared with [68Ga]Ga-DOTA-FAPI-04. Immunofluorescent and immunohistochemical staining and western blot assay were performed to confirm FAP expression in xenograft tumors. [68Ga]Ga-DOTA-GPFAPI-04 exhibited a radiochemical purity of > 99% and high stability in PBS and FBS. [68Ga]Ga-DOTA-GPFAPI-04 had higher hydrophilic property than [68Ga]Ga-DOTA-FAPI-04 (-4.09 ± 0.05 vs -3.45 ± 0.05). Small animal PET and semi-quantitative analysis revealed Panc-1 xenograft tumor displayed higher tumor uptake of [68Ga]Ga-DOTA-GPFAPI-04 and tumor-to-background ratios compared to A549 xenograft tumor, consistent with the results of immunofluorescence, immunohistochemistry, and western blot. Moreover, [68Ga]Ga-DOTA-GPFAPI-04 demonstrated higher tumor accumulation and longer tumor retention than [68Ga]Ga-DOTA-FAPI-04 in both Panc-1 and A549 xenograft tumors. Furthermore, the FAP-binding specificity of [68Ga]Ga-DOTA-GPFAPI-04 was confirmed in vivo by co-injection of unlabeled GPFAPI-04. [68Ga]Ga-DOTA-GPFAPI-04 showed more favorable in vivo tumor imaging and longer tumor retention compared to [68Ga]Ga-DOTA-FAPI-04, which has high potential to be a promising PET probe for detecting FAP-positive tumors.

Gadolinium‐Manganese‐Based Nanoplatform Reverses Radiotherapy Resistant Factors for Radiotherapy Sensitization and Computed Tomography/Magnetic Resonance Dual‐Modal Imaging

Insufficient reactive oxygen species originating from hypoxia and high glutathione (GSH) in the tumor microenvironment (TME) is an important reason for radiotherapy (RT) resistance. Currently, radiosensitizers that remodel TME are widely investigated to enhance RT. However, developing an effective nano‐radiosensitization system that removes radiotherapy‐resistant factors from TME to boost RT effect while visualizing tumor imaging to aid therapy remains a challenge. Herein, MnO2 nanosheets are grown on the surface of ultrasmall Eu‐doped NaGdF4 (NaGdF4:Eu3+) nanoparticles and modified by biocompatible DSPE‐PEG2000 to prepare NaGdF4:Eu3+@MnO2@PEG nanoparticles (denoted as GMP NPs) as a radiosensitizer, which not only can reverse the TME by degrading H2O2 to produce oxygen and consuming high GSH but also achieve computed tomography (CT)and magnetic resonance (MR) imaging. When GMP NPs synergize with X‐ray, a better antitumor effect is achieved in both HeLa cells and tumor‐bearing mice, compared with X‐ray alone. In addition, both paramagnetic Mn2+ ionsproduced by decomposing MnO2 in TME and NaGdF4:Eu3+ nanoparticles enhance T1‐weighted MR imaging. NaGdF4:Eu3+ nanoparticles containing high atomic number of Gd/Eu effectively attenuate X‐ray to enhance CT imaging. The work provides new insights for developing an efficient RT sensitization platform integrating antitumor therapeutic effect as well as CT/MR dual‐modal imaging.

A Novel Hybrid Machine Learning-Based System Using Deep Learning Techniques and Meta-Heuristic Algorithms for Various Medical Datatypes Classification.

Medicine is one of the fields where the advancement of computer science is making significant progress. Some diseases require an immediate diagnosis in order to improve patient outcomes. The usage of computers in medicine improves precision and accelerates data processing and diagnosis. In order to categorize biological images, hybrid machine learning, a combination of various deep learning approaches, was utilized, and a meta-heuristic algorithm was provided in this research. In addition, two different medical datasets were introduced, one covering the magnetic resonance imaging (MRI) of brain tumors and the other dealing with chest X-rays (CXRs) of COVID-19. These datasets were introduced to the combination network that contained deep learning techniques, which were based on a convolutional neural network (CNN) or autoencoder, to extract features and combine them with the next step of the meta-heuristic algorithm in order to select optimal features using the particle swarm optimization (PSO) algorithm. This combination sought to reduce the dimensionality of the datasets while maintaining the original performance of the data. This is considered an innovative method and ensures highly accurate classification results across various medical datasets. Several classifiers were employed to predict the diseases. The COVID-19 dataset found that the highest accuracy was 99.76% using the combination of CNN-PSO-SVM. In comparison, the brain tumor dataset obtained 99.51% accuracy, the highest accuracy derived using the combination method of autoencoder-PSO-KNN.

Present challenges and surveillance of artificial intelligence in neuro-oncology

Brain tumors are evaluated, characterized, and monitored using diagnostic imaging. However, because these tumors are so diverse, there are still several difficulties in each group. This might involve differences in the biology of the cancer that are linked to varying intensities of cellular invasion, proliferation, and necrosis, all of which have distinct imaging appearances. Due to these changes, tumor evaluation, including segmentation, surveillance, and molecular characterizations, has become more complex. Even though various rule-based techniques have been put into practice to relate to tumor appearance and size, these techniques naturally reduce the vast quantity of tumor imaging data to a small number of variables. Due to their efficacy in resolving image-based problems, approaches in artificial intelligence, machine learning, and deep learning have found increased use in computer vision tasks, such as tumor imaging. This section aims to provide an overview of some of these developments in tumor imaging.

Total-body dynamic PET/CT imaging reveals kinetic distribution of [13N]NH3 in normal organs.

To systematically investigate kinetic metrics and metabolic trapping of [13N]NH3 in organs. Eleven participants performed total-body [13N]NH3 dynamic positron emission tomography (PET). Regions of interest were drawn in organs to obtain time-to-activity curves (TACs), which were fitted with an irreversible two-tissue compartment model (2TC) to investigate constant rates K1, k2 and k3, and to calculate Ki. Additionally, one-tissue compartment model using full data (1TCfull) and the first four minutes of data (1TC4min) were fitted to TAC data. K1 and k2 were compared among different models to assess [13N]NH3 trapping in organs. Kinetic rates of [13N]NH3 varied significantly among organs. The mean K1 ranged from 0.049 mL/cm3/min in the muscle to 2.936 mL/cm3/min in the kidney. The k2 and k3 were lowest in the liver (0.001min- 1) and in the pituitary (0.009min- 1), while highest in the kidney (0.587min- 1) and in the liver (0.800min- 1), respectively. The Ki was largest in the myocardium (0.601 ± 0.259 mL/cm3/min) while smallest in the bone marrow (0.028 ± 0.022 mL/cm3/min). Three groups of organs with similar kinetic characteristics were revealed: (1) the thyroid, the lung, the spleen, the pancreas, and the kidney; (2) the liver and the muscle; and (3) the cortex, the white matter, the cerebellum, the pituitary, the parotid, the submandibular gland, the myocardium, the bone, and the bone marrow. Obvious k3 was identified in multiple organs, and significant changes of K1 in multiple organs and k2 in most organs were found between 2TC and 1TCfull, but both K1 and k2 were comparable between 2TC and 1TC4min. The kinetic rates of [13N]NH3 differed among organs with some have obvious 13N-anmmonia trapping. The normal distribution of kinetic metrics of 13N-anmmonia in organs can serve as a reference for its potential use in tumor imaging.