Molecular Imaging Research Articles

PH-responsive albumin-mimetic synthetic nanoprobes for magnetic resonance/fluorescence imaging of thyroid cancer.

The combination of magnetic resonance and fluorescence imaging in dual-modality imaging not only resolves the limitations of conventional single molecular imaging techniques in terms of specificity, sensitivity, and resolution but also expands the possibilities of molecular imaging techniques in diagnostics and therapeutic monitoring. Herein, a novel pH-responsive magnetic resonance/near-infrared fluorescence (MR/NIRF) nanoprobe (MnO2@BSA-Cy5.5) was successfully prepared by biomineralizing manganese dioxide (MnO2) with bovine serum albumin (BSA) while coupling fluorescent dye Cy5.5 for precise tumor detection and visualization. The synthesized MnO2@BSA-Cy5.5 nanoprobes were spherical particles of approximately 22.62 ± 3.31 nm in size, and their relaxation rates and T1 imaging signals were activated-enhanced in an acidic environment. Cytotoxicity assay and hematoxylin and eosin staining demonstrated that MnO2@BSA-Cy5.5 had low cytotoxicity and good biocompatibility. More importantly, active targeting via solid tumor albumin-binding protein receptor and enhanced permeability and retention effect, the probe can be specifically aggregated to the tumor site of the 8305C tumor model and exhibit excellent MR/NIRF imaging properties. Our results show that MnO2@BSA-Cy5.5 has high resolution and sensitivity in tumor imaging and is expected to be applied as an MR/NIRF contrast agent for accurate diagnosis of thyroid cancer.

Advances in Molecular Imaging for Renal Tumors.

Advances in Molecular Imaging for Renal Tumors.

Abstract PS05-04: [89Zr]Trastuzumab-PET/MRI to Characterize HER2+ Breast Cancer: A Quantitative Approach on Tumor Heterogeneity

Abstract Introduction: Molecular imaging of human epidermal receptor 2 (HER2) aims to overcome limitations of traditional HER2 assessment through biopsy, including invasiveness and inability to detect intra and inter-tumoral spatial heterogeneity. Prior human studies suggest that [89Zr]Trastuzumab-positron emission tomography (PET) imaging can effectively differentiate HER2 lesions (Dehdashti et al, Breast Cancer Res. Treat. 2018). Commonly, CT complements PET for anatomical reference, however, integrating MRI enables the sensitivity of soft-tissue contrast required for anatomic and morphological breast imaging and can provide for quantitative multiparametric characterization. Diffusion weighted-MRI (DW-MRI) contributes to tumor characterization by assessing intratumoral cellularity via the apparent diffusion coefficient (ADC), and can be combined with molecular expression from HER2-PET. We present preliminary results in 13 patients with HER2 PET/MRI to define tumor and normal tissue imaging metrics. Methods: A phase II clinical trial assessing the feasibility of [89Zr]trastuzumab-PET with simultaneous quantitative DW-MRI to enhance understanding of tumor heterogeneity in patients with HER2-positive metastatic breast cancer. 13 patients (ages 40-70; mean 60) with HER2-positive breast cancer based on prior biopsy underwent whole-body [89Zr]trastuzumab-PET/MR imaging (5 ± 1 days post-injection of radiopharmaceutical) during the course of HER2-directed therapy. Normal organ and tumor regions of interest (ROI) were identified on concurrently acquired whole-body T1-weighted MRI for ADC (cellularity) and standardized uptake value (SUV, PET uptake) mean quantification. Tumor presence was confirmed via bone scintigraphy, FDG-PET/CT, or contrast-enhanced MRI. Non-parametric T-tests compared lesions to normal organs. Lesions greater than 30 mm in diameter underwent multiparametric intratumoral habitat analysis. Using the median HER2 values, tumors were evaluated for heterogeneity of high and low HER2 expression in conjunction with ADC. Long-term treatment response evaluation is ongoing. Results: Mean [89Zr]trastuzumab uptake, SUV, and ADC values for normal tissue were summarized in Table 1. All tumors demonstrated higher overall uptake of [89Zr]trastuzumab (bone: p=0.019, brain: p=0.014, breast: p=0.069, juxtapulmonary: p=0.026) and increased ADCmean values (bone: p=0.002, brain: p=0.5, breast: p=0.03, juxtapulmonary: p=0.037), in comparison to matched normal organs. Notably, one of five patients with a breast lesion, who completely responded to HER2 targeted therapy, exhibited the highest breast lesion SUVmean. Brain and lymph node lesions demonstrated intratumoral heterogeneity of HER2 expression. Conclusion: Our study demonstrates the potential value of quantitative MRI along with molecular imaging to characterize metastatic HER2+ breast cancer and evaluate intratumoral heterogeneity. We underscore the importance of standardizing processing techniques and contribute to this effort by summarizing [89Zr]trastuzumab uptake and cellularity values of normal physiological uptake. Higher SUVmean and ADC mean values observed in lesions, compared to normal tissue, highlight their potential roles in intratumoral classification. While studies have shown the utility of [89 Zr]trastuzumab-PET/CT, our findings demonstrate that integrated DW-MRI can aid in tumor classification. Table 1: Physiological 89Zr-Trastuzumab Uptake (SUVmean) and Apparent Diffusion Coefficient (ADCmean) in Healthy Tissues Citation Format: Ameer Mansur, Moozhan Nikpanah, Johnathan McConathy, Erica Stringer-Reasor, Gabrielle Rocque, Ahmed Elkhanany, Katia Khoury, Nusrat Jahan, Suzanne Lapi, Anna Sorace. [89Zr]Trastuzumab-PET/MRI to Characterize HER2+ Breast Cancer: A Quantitative Approach on Tumor Heterogeneity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-04.

Abstract PO2-07-07: The role of PET imaging with [18F]16α-fluoro-17β-fluoroestradiol in predicting response to endocrine therapies in patients with breast cancer

Abstract Background Fluoroestradiol F18 is a radioactive diagnostic agent (18F-FES) used with positron emission tomography (PET) imaging to detect estrogen-receptor (ER)-positive lesions in patients with breast cancer. Convened by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an expert working group published appropriate use criteria (AUC) for 18F-FES PET including, but not limited to, use of 18F-FES for selection of endocrine therapies. Quantitative determination of ER status, and thus treatment response, has the potential to prevent ineffective courses of endocrine therapies and associated therapeutic/financial burden. This meta-analysis reviewed the AUC-cited studies to assess the utility of 18F-FES in predicting treatment response to endocrine therapies. Methods Eight studies cited in the AUC were selected based on having comparable 18F-FES PET standardized uptake values (SUV) and progression-free survival (PFS) measures, and one additional study was included upon further systematic search of the same selected parameters defined in the AUC. With the nine studies (n = 327), we conducted three investigations to explore the association between: (1) the patient baseline 18F-FES PET SUVmean, across all lesions or across up to seven of the most intense lesions, and patient response to endocrine therapy (response/no response); (2) in the same population as investigation 1, the change (%) in 18F-FES PET SUV from baseline to at 7 to 10 days post-treatment; (3) the 18F-FES interlesional heterogeneity and PFS (months). Interlesional heterogeneity was qualitatively defined as patients displaying both 18F-FES positive and negative lesions versus those with all FES-positive lesions. Results A fixed effects model was used to analyze three studies (n = 102). Findings reveal that patients who responded to endocrine therapy had a significantly higher baseline SUVmean versus non-responders (mean difference 0.91; CI 95% 0.49 to 1.34; P < 0.001); a sensitivity analysis was conducted via random effects modelling and revealed similar results (mean difference 0.92; CI 95% 0.48 to 1.36; P < 0.001). This was consistent with findings from an additional analysis performed on two papers (n = 62), whereby odds ratio estimates indicated that a response to therapy is 89% less likely to occur when baseline 18F-FES SUVmax is < 1.5 (OR 0.11; CI 95% 0.02 to 0.72 P = 0.02). Findings from the analysis of mean percentage change in 18F-FES SUV from baseline to 7-10 days post-treatment initiation showed no significant difference in the percentage change of SUV observed between responders and non-responders (mean difference -0.22; 95% CI -0.69 to 0.26; P = 0.37). The final heterogeneity analysis revealed higher median PFS in all FES-positive cohort, suggesting that this group may respond better to endocrine therapy (Table 1). Conclusion The AUC states that the presence of ER by immunohistochemistry may not be the optimal predictive biomarker for the success of endocrine therapies. Our findings support this statement, as a significantly higher baseline SUVmean of 18F-FES may serve as a predictive biomarker for endocrine therapy response. Patients with a 18F-FES lesion SUVmax < 1.5 are 89% less likely to respond to endocrine therapies; patients demonstrating heterogeneity (FES+/FES- lesions) have a lower median PFS, reinforcing the predictive value of 18F-FES. Table 1. Median PFS scores from FES heterogeneity analysis *Patients with all FES positive lesions were categorised by the median ratio of FES/FDG SUVmax into low FES/FDG ( <0.96), and high FES/FDG (>0.96); only patients with FES/FDG of >0.96 were included in the positive lesions arm. Citation Format: Nicholas DiGregorio, Christine Brand, Dustin Dunham, Eleanor McManus. The role of PET imaging with [18F]16α-fluoro-17β-fluoroestradiol in predicting response to endocrine therapies in patients with breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-07-07.

Defining oligometastatic state in uro-oncological cancers.

Oligometastatic tumors illustrate a distinct state between localized and systematic disease and might harbor unique biologic features. Moreover, these tumors represent a different clinical entity, with a potential of long-term disease control or even cure, therefore they receive growing attention in the field of urologic oncology. Currently, there is no consensus on the definition of oligometastatic prostate cancer, most experts limit it to a maximum of three to five lesions and involvement of no more than two organs, excluding visceral metastases. Quality data on oligometastatic bladder cancer is scarce, however, a consensus of experts defined it as a maximum of three metastatic lesions, either resectable or suitable for stereotactic therapy, without restrictions to the number of organs involved. As for kidney cancer, a maximum number of five metastases, without limitations to the location are defined as oligometastatic, with an important implication of timing of developing metastases since diagnosis of the primary tumor. Defining oligometastatic state among urological tumors reflecting their distinct biological and clinical behavior is crucial to establish a sound framework for future clinical trials, and to facilitate guideline and policy formulation for improved patient care. Advancements in molecular imaging are expected to transform the field of oligometastatic urologic tumors in the future.

Abstract PO4-19-02: Genetic risk estimation in breast cancer and assessing health disparities

Abstract Background: Breast Cancer (BC) incidence and the distribution of BC risk factors vary between racial and ethnic groups within the United States. It has been demonstrated that providing education on individualized breast cancer risk will improve patient uptake to recommended BC screening and prevention strategies. Most clinical risk assessment tools, including the validated IBIS model were derived from data using non-Hispanic white women. Consortia have also now identified over 300 common genetic susceptibility loci for BC, summarized by the polygenic risk score (PRS). When combined with clinical risk assessment tools, such as the IBIS or BCRAT models, the PRS can further refine risk estimation for patients. To date, most studies on the use of PRS have been done in non-Hispanic white women. While these PRS still perform well in racial minorities, there has been a recognized need to improve racial and ethnic diversity in genomic research cohorts. Herein, we aim to combine clinical risk assessment models that are already used in routine clinical practice with information derived from PRS testing in women of racial minorities to determine if this can improve risk estimation, patient understanding, and uptake to recommended breast cancer screening and prevention strategies. Design: This is a minimal risk prospective study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the information provided by the PRS influenced patient decisions regarding recommended BC screening and prevention. Patients will have IBIS and BCRAT risks calculated at baseline visit. A survey of patient perceptions/understanding of risk, intention to undergo screening, and use of preventive medicine is completed after baseline visit prior to receiving the PRS results. Blood sample is obtained at baseline and DNA samples are analyzed for approximately 300 SNPs on a custom-designed, targeted SNP panel from ThermoFisher Scientific by the Mayo Clinic Genomics Laboratory. This PRS result is then combined with the clinical risk assessments (IBIS and BCRAT scores) using the R package Individualized Coherent Absolute Risk Estimators (iCare) tool to provide a new estimate of breast cancer risk for 5year, 10year, and lifetime risk. Patients are seen for follow-up to review results and then complete a second survey to assess their understanding of the results, BC risk, and how the PRS impacted their decision to undergo screening/prevention strategies. Eligibility Criteria: Women who self-identify as African American/Black or Hispanic/Latinx between 30-75 years old with any of the following: 1.)IBIS score of ≥5% for the 10 year risk OR BCRAT score of ≥ 3 % for the 5 year risk. 2.) History of biopsy proven atypical hyperplasia 3.) History of biopsy proven lobular carcinoma in situ. Specific Aims: Aim 1: The primary aim of this study is to explore if the addition of PRS to the BCRAT and IBIS score will improve intentions to undergo recommended breast cancer screening strategies such as mammography, MRI, or molecular breast imaging in women of underserved racial minorities Aim 2: To explore if the addition of the PRS to the BCRAT and IBIS risk score will aid women of racial minorities in deciding whether to take preventative endocrine therapy. Aim 3: To understand how individualized risk assessment and information on PRS may alter perceived risk of breast cancer. Statistical Methods Analysis will be mostly descriptive. Continuous variables will be summarized as mean (standard deviation) or median (range) and categorical variables will be reported as frequency (percentage). Kaplan-Meier method will be used to estimate the long-term cumulative risk of cancer. Current Accrual: 3. Target Accrual: 50 Citation Format: Lauren Cornell, Sandhya Pruthi, Linda Hasadsri, Sarah McLaughlin. Genetic risk estimation in breast cancer and assessing health disparities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-02.

Abstract PO1-07-10: Blood Based Early Cancer Detection Assay

Abstract Background: Breast cancer screening programs utilizing mammography have been shown to be highly effective in identifying breast cancer in women over the age of 40. High breast density is an independent risk factor for breast cancer and makes mammograms more difficult to interpret, decreasing their sensitivity. In the spring of 2023, the FDA, who certifies all mammography facilities under the Mammography Quality Standards Act, updated its regulations to require that breast density status be reported to all individuals receiving a mammogram. The new guidelines now require individuals with dense breast tissue be notified of this status. The guidelines also recommend these women discuss additional screening options with their healthcare providers1. These additional screening options may include breast tomosynthesis, breast MRI, breast ultrasound, and/or molecular breast imaging. Many of these options require additional exposure to radiation, are expensive, and are not equitably available across the country. In addition, they all require a follow-up appointment. Compliance can be challenging given the top barriers to mammography cited include the need for transportation, child-care, and the ability to take time off from work2. Genece Health is developing a simpler and less expensive screening solution that identifies the presence of early to late-stage breast cancer using cfDNA from a single blood draw. The Genece Health assay utilizes an algorithm that leverages Artificial Intelligence and Machine Learning to analyze fragment size and end motif patterns in cfDNA as well as regional mutational density to detect presence of ctDNA originating from breast cancer. This algorithm provides highly sensitive and specific results in a preliminary data set. Methods: The preliminary data set, presented herein, is a cohort of over 50 retrospective breast cancer plasma samples and over 100 presumed normal samples. The breast cancer samples were collected at all stages of progression, from stage 0, or ductal carcinoma in situ (DCIS), through stage IV. The majority ( >50%) were from stage I breast cancer. 400 µL of double spun plasma, collected in Streck BCT devices, was processed to purify and isolate cfDNA. cfDNA was used to create WGS libraries that were sequenced on a NovaSeq 6000. Sequence data were analyzed using a bioinformatics pipeline that yields an ensemble probability that correlates to the presence or absence of ctDNA from breast cancer. Results: The Genece Health assay and algorithm performed with a specificity greater than 85%. With this specificity, the assay had a sensitivity greater than 85% in samples from stages II to IV and a slightly lower sensitivity in stage 0 and I samples. Follow-up analyses were conducted to stratify performance based on breast cancer type (e.g. invasive ductal carcinoma vs invasive lobular carcinoma) and HR, PR, and HER2 status (e.g. HER2-negatives vs HER2-positives). Conclusions: The presented preliminary data indicate that the Genece Health technology can be leveraged as a complement to mammography in indications, such as dense breast tissue, where there is an unmet need for an easy and cost-effective way to monitor for breast cancer. The ability to have a blood-based test to complement mammography could reduce the access barriers most cited by females in the United States. Follow-up studies with greater numbers of samples and additional training and optimizations of the algorithm will yield performance improvements that allow the assay to detect all types and stages of breast cancer.

Triple Sensing Modes for Triggered β-Galactosidase Activity Assays Based on Kaempferol-Deduced Silicon Nanoparticles and Biological Imaging of MCF-7 Breast Cancer Cells.

β-Galactosidase (β-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor β-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine β-Gala activity effectively. Via the sensing performance, the catalytic activity of β-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-β-d-galactopyranoside (KOβDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing β-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of β-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.

Abstract PO5-18-01: Cancer Detection Rate Meta-Analysis Comparison of Contemporary Dense-Breast Supplemental Screening Modalities

Abstract We performed a meta-analysis of the cancer detection rates from 24 published reports in dense breasts for all contemporary and FDA-approved imaging modalities (DM, DBT, U/S, CEM, MBI, MRI) available for supplemental breast cancer screening. This information is critical to the 40% of women with BIRADS categorized dense breasts (C,D) receiving breast cancer screening. In the paper an analysis of the net lives saved using a benefit-to-risk comparison of the ionizing imaging modalities (DM, DBT and MBI) is also presented and the safety of each technique is described. Note that it is well accepted that carcinogenic risk associated with ionizing radiation doses of < 100 mSv are considered too small to be detected or altogether non-existant. Recently, with FDA's federal MQSA requirements changing to mandate notification of womens' dense-breast status (C,D), awareness has grown substantially about the dismal cancer detection performances of DM, DBT and U/S which degrades substantially with increasing breast density. Additionally, this May 2023, federal legislation was introduced in congress. The Find It Early Act (HR3086), should it become law in 2024, will require that healthcare payors cover costs for supplemental screening of women with dense breasts. Knowing and understanding the arsenal of the highest performing imaging modalities (based on cancer detection rates (CDR), Sensitivity, Specificity, NPV) is critically important for all patients and physicians caring for them. The volume of women qualifying for supplemental breast screening is expected to be managed by existing and growing numbers of all the best performing available technologies and approaches. Since the analysis is based on numerous others’ clinical trials of CDRs evaluating the various modalities in millions of women, this comprehensive analysis presents a level playing field for comparison. The top-three high performing imaging modalities (CEM, MBI, MRI) should be used to increase the number of early-stage cancers found in order to substantially decrease mortality, decrease patient trauma, decrease procedures, and decrease costs per cancer detected, all at overall benefit to the patients, the hospitals, the payors and provide long-term benefits to society. Table. Summary of Relative Cancer Detection Rates (per 1,000 women) in Dense-Breast Supplemental Screening Results of multiple pairwise meta-analyses comparing various modalities (Digital Breast Tomosynthesis; Ultrasound; Contrast Enhanced Mammography; Molecular Breast Imaging; Magnetic Resonance Imaging) to Digital Mammography. “X” represents the second supplemental screening modality compared to DM. “+X” means the combination of DM+X. Two normalizations are compared: “CDR Ratio model” and “Incremental CDR model.” Table. Net Lives Saved by Ionizing Radiation Imaging Modalities per Age Decade Citation Format: Martin Tornai, James Hugg, Bradley Patt, Chin-Tu Chen, Eduardo Santos, Alaattin Erkanli, Samantha Morrison, Matthew Covington. Cancer Detection Rate Meta-Analysis Comparison of Contemporary Dense-Breast Supplemental Screening Modalities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-01.

Multiwavelength laser diode based portable photoacoustic and ultrasound imaging system for point of care applications.

Vascular diseases are a leading cause of death and disability worldwide. Despite having precursor conditions like peripheral arterial disease (PAD), they are often only diagnosed after the onset of stroke or heart attack. Low-cost, portable, noninvasive, point-of-care (POC), label-free assessment of deep vascular function benefits PAD diagnosis, especially in resource poor settings of the world. Doppler ultrasound-based blood flow measurements can diagnose PAD, albeit with limited sensitivity and specificity. To overcome this, here, we propose the first-of-its-kind dual-modality photoacoustic-and-ultrasound (PAUS) imaging system that integrates a multiwavelength pulsed laser diode (PLD) with a compact ultrasound data acquisition unit. The mesoscopic imaging depth of the portable PLD-PAUS system was validated using tissue phantoms, and its multispectral photoacoustic imaging capabilities were validated using an atherosclerosis-mimicking phantom. Furthermore, we demonstrated high-contrast volumetric in vivo photoacoustic imaging of rodent abdominal vasculature and quantified vessel reactivity due to hypercapnia stimulation. The multiparametric functional and molecular imaging capabilities of the PLD-PAUS system holds promise for POC applications.

Removal of endothelial surface-associated von villebrand factor suppresses accelerate datherosclerosis after myocardial infarction

BackgroundThromboinflammation involving platelet adhesion to endothelial surface-associated von Willebrand factor (VWF) has been implicated in the accelerated progression of non-culprit plaques after MI. The aim of this study was to use arterial endothelial molecular imaging to mechanistically evaluate endothelial-associated VWF as a therapeutic target for reducing remote plaque activation after myocardial infarction (MI).MethodsHyperlipidemic mice deficient for the low-density lipoprotein receptor and Apobec-1 underwent closed-chest MI and were treated chronically with either: (i) recombinant ADAMTS13 which is responsible for proteolytic removal of VWF from the endothelial surface, (ii) N-acetylcysteine (NAC) which removes VWF by disulfide bond reduction, (iii) function-blocking anti-factor XI (FXI) antibody, or (iv) no therapy. Non-ischemic controls were also studied. At day 3 and 21, ultrasound molecular imaging was performed with probes targeted to endothelial-associated VWF A1-domain, platelet GPIbα, P-selectin and vascular cell adhesion molecule-1 (VCAM-1) at lesion-prone sites of the aorta. Histology was performed at day 21.ResultsAortic signal for P-selectin, VCAM-1, VWF, and platelet-GPIbα were all increased several-fold (p < 0.01) in post-MI mice versus sham-treated animals at day 3 and 21. Treatment with NAC and ADAMTS13 significantly attenuated the post-MI increase for all four molecular targets by > 50% (p < 0.05 vs. non-treated at day 3 and 21). On aortic root histology, mice undergoing MI versus controls had 2–4 fold greater plaque size and macrophage content (p < 0.05), approximately 20-fold greater platelet adhesion (p < 0.05), and increased staining for markers of platelet transforming growth factor-β1 signaling. Accelerated plaque growth and inflammatory activation was almost entirely prevented by ADAMTS13 and NAC. Inhibition of FXI had no significant effect on molecular imaging signal or plaque morphology.ConclusionsPlaque inflammatory activation in remote arteries after MI is strongly influenced by VWF-mediated platelet adhesion to the endothelium. These findings support investigation into new secondary preventive therapies for reducing non-culprit artery events after MI.

Whole Reconstruction-Free System Design for Direct Positron Emission Imaging From Image Generation to Attenuation Correction.

Direct positron emission imaging (dPEI), which does not require a mathematical reconstruction step, is a next-generation molecular imaging modality. To maximize the practical applicability of the dPEI system to clinical practice, we introduce a novel reconstruction-free image-formation method called direct μCompton imaging, which directly localizes the interaction position of Compton scattering from the annihilation photons in a three-dimensional space by utilizing the same compact geometry as that for dPEI, involving ultrafast time-of-flight radiation detectors. This unique imaging method not only provides the anatomical information about an object but can also be applied to attenuation correction of dPEI images. Evaluations through Monte Carlo simulation showed that functional and anatomical hybrid images can be acquired using this multimodal imaging system. By fusing the images, it is possible to simultaneously access various object data, which ensures the synergistic effect of the two imaging methodologies. In addition, attenuation correction improves the quantification of dPEI images. The realization of the whole reconstruction-free imaging system from image generation to quantitative correction provides a new perspective in molecular imaging.

A review of recent advances in the use of complex metal nanostructures for biomedical applications from diagnosis to treatment.

Complex metal nanostructures represent an exceptional category of materials characterized by distinct morphologies and physicochemical properties. Nanostructures with shape anisotropies, such as nanorods, nanostars, nanocages, and nanoprisms, are particularly appealing due to their tunable surface plasmon resonances, controllable surface chemistries, and effective targeting capabilities. These complex nanostructures can absorb light in the near-infrared, enabling noteworthy applications in nanomedicine, molecular imaging, and biology. The engineering of targeting abilities through surface modifications involving ligands, antibodies, peptides, and other agents potentiates their effects. Recent years have witnessed the development of innovative structures with diverse compositions, expanding their applications in biomedicine. These applications encompass targeted imaging, surface-enhanced Raman spectroscopy, near-infrared II imaging, catalytic therapy, photothermal therapy, and cancer treatment. This review seeks to provide the nanomedicine community with a thorough and informative overview of the evolving landscape of complex metal nanoparticle research, with a specific emphasis on their roles in imaging, cancer therapy, infectious diseases, and biofilm treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Diagnostic Tools > Diagnostic Nanodevices.

An Update on MR Spectroscopy in Cancer Management: Advances in Instrumentation, Acquisition, and Analysis.

MR spectroscopy (MRS) is a noninvasive imaging method enabling chemical and molecular profiling of tissues in a localized, multiplexed, and nonionizing manner. As metabolic reprogramming is a hallmark of cancer, MRS provides valuable metabolic and molecular information for cancer diagnosis, prognosis, treatment monitoring, and patient management. This review provides an update on the use of MRS for clinical cancer management. The first section includes an overview of the principles of MRS, current methods, and conventional metabolites of interest. The remainder of the review is focused on three key areas: advances in instrumentation, specifically ultrahigh-field-strength MRI scanners and hybrid systems; emerging methods for acquisition, including deuterium imaging, hyperpolarized carbon 13 MRI and MRS, chemical exchange saturation transfer, diffusion-weighted MRS, MR fingerprinting, and fast acquisition; and analysis aided by artificial intelligence. The review concludes with future recommendations to facilitate routine use of MRS in cancer management. Keywords: MR Spectroscopy, Spectroscopic Imaging, Molecular Imaging in Oncology, Metabolic Reprogramming, Clinical Cancer Management © RSNA, 2024.

What do the mushroom bodies do for the insect brain? Twenty-five years of progress.

In 1998, a special edition of Learning & Memory was published with a discrete focus of synthesizing the state of the field to provide an overview of the function of the insect mushroom body. While molecular neuroscience and optical imaging of larger brain areas were advancing, understanding the basic functioning of neuronal circuits, particularly in the context of the mushroom body, was rudimentary. In the past 25 years, technological innovations have allowed researchers to map and understand the in vivo function of the neuronal circuits of the mushroom body system, making it an ideal model for investigating the circuit basis of sensory encoding, memory formation, and behavioral decisions. Collaborative efforts within the community have played a crucial role, leading to an interactive connectome of the mushroom body and accessible genetic tools for studying mushroom body circuit function. Looking ahead, continued technological innovation and collaborative efforts are likely to further advance our understanding of the mushroom body and its role in behavior and cognition, providing insights that generalize to other brain structures and species.

Emerging Trends in Hybrid Nanoparticles: Revolutionary Advances and Promising Biomedical Applications.

Modern nanostructures must fulfill a wide range of functions to be valuable, leading to the combination of various nano-objects into hierarchical assemblies. Hybrid Nanoparticles (HNPs), comprised of multiple types of nanoparticles, are emerging as nanoscale structures with versatile applications. HNPs offer enhanced medical benefits compared to basic combinations of distinct components. They address the limitations of traditional nanoparticle delivery systems, such as poor water solubility, nonspecific targeting, and suboptimal therapeutic outcomes. HNPs also facilitate the transition from anatomical to molecular imaging in lung cancer diagnosis, ensuring precision. In clinical settings, the selection of nanoplatforms with superior reproducibility, cost-effectiveness, easy preparation, and advanced functional and structural characteristics is paramount. This study aims toextensively examine hybrid nanoparticles, focusing on their classification, drug delivery mechanisms, properties of hybrid inorganic nanoparticles, advancements in hybrid nanoparticle technology, and their biomedical applications, particularly emphasizing the utilization of smart hybrid nanoparticles. PHNPs enable the delivery of numerous anticancer, anti-leishmanial, and antifungal drugs, enhancing cellular absorption, bioavailability, and targeted drug delivery while reducing toxic side effects.

Positron Emission Tomography Imaging of Tumor Proliferation and DNA Repair.

Positron emission tomography (PET) is an established tool for molecular imaging of cancers, and its role in diagnosis, staging, and phenotyping continues to evolve and expand rapidly. PET imaging of increased glucose utilization with 18F-fluorodeoxyglucose is now entrenched in clinical oncology practice for improving prognostication and treatment response assessment. Additional critical processes for cancer cell survival can also be imaged by PET, helping to inform individualized treatment selections for patients by improving our understanding of cell survival mechanisms and identifying relevant active mechanisms in each patient. The critical importance of quantifying cell proliferation and DNA repair pathways for prognosis and treatment selection is highlighted by the nearly ubiquitous use of the Ki-67 index, an established histological quantitative measure of cell proliferation, and BRCA mutation testing for treatment selection. This review focuses on PET advances in imaging and quantifying cell proliferation and poly(ADP-ribose)polymerase expression that can be used to complement cancer phenotyping approaches that will identify the most effective treatments for each individual patient.

Molecular Imaging for Breast Cancer Phenotyping: Tc-99m sestamibi Scintigraphy cannot be Missed.

Molecular Imaging for Breast Cancer Phenotyping: Tc-99m sestamibi Scintigraphy cannot be Missed.

Use of Molecular Imaging to Further Investigate PI-RADS 3 Lesions.

Use of Molecular Imaging to Further Investigate PI-RADS 3 Lesions.

Phase 2 Clinical Trial of VGT-309 for Intraoperative Molecular Imaging During Pulmonary Resection

BackgroundAdvances in intraoperative molecular imaging (IMI) may improve surgical outcomes when resecting tumors in the lung. A single-center trial was conducted using VGT-309, a cathepsin-targeted near-infrared imaging agent that causes lung nodules to fluoresce during surgical resection. The end point of this phase 2 study was to evaluate the frequency that IMI with VGT-309 resulted in a clinically significant event (CSE): localization of pulmonary nodules, discovery of unsuspected additional cancers, or identification of positive margins. MethodsPatients undergoing surgical resection for known or suspected cancer in the lung received VGT-309 (0.32 mg/kg) preoperatively. During the surgical procedure, localization and resection of the nodules were performed using standard surgical techniques. Near-infrared imaging was then used to localize nodules, seek occult lesions, and assess resection margins. Efficacy was measured by the frequency of CSEs. ResultsOf the 40 patients who underwent pulmonary resection with VGT-309, 17 (42.5%) had at least 1 CSE. Near-infrared imaging identified lesions not found by standard surgical methods in 16 patients, additional cancers not found by preoperative imaging in 1 patient, and margins within 5 mm of the closest staple line in 2 patients. VGT-309 performance was tested across a broad range of tumor types and commercial near-infrared imaging systems. VGT-309 appeared safe, well-tolerated, with no infusion reactions, and no drug-related serious adverse events. ConclusionsThis phase 2 study demonstrated the utility of IMI with VGT-309 in localizing pulmonary nodules, recognizing synchronous lesions, and identifying positive margins. A multi-institutional study will further evaluate the efficacy of VGT-309.