Molecular Imaging And Biology[JOURNAL]
Sun
200 papers
Dual Targeting of Neuropilin-1 and Glucose Transporter for Efficient Fluorescence Imaging of Cancer.
Zhu J, Zhou C, Yang J … +1 more , Wang Z
Mol Imaging Biol · 2025 Apr · PMID 40048021 · Full text
PURPOSE: Early diagnosis and complete resection of cancer are pivotal for enhancing patient survival rates and prognosis. However, a significant current challenge lies in the lack of specific imaging probes for the ident...
PURPOSE: Early diagnosis and complete resection of cancer are pivotal for enhancing patient survival rates and prognosis. However, a significant current challenge lies in the lack of specific imaging probes for the identifying various tumor types. The expression levels of neuropilin-1 (NRP1) and glucose transporter 1 (GLUT1) in most tumors, including breast cancer, are closely linked to tumor proliferation and metastasis. This study seeks to develop a novel near-infrared fluorescence (NIRF) probe aimed at precise tumor detection by targeting NRP1 and GLUT1. PROCEDURES: G was conjugated with N-PEG-ALKADK and 2-Azido-2-deoxy-D-glucose to synthesize the NGF probe. The spectral properties (fluorescence and absorbance spectra) of NGF were studied in both methanol and water. The targeting specificity of NGF towards NRP1 and GLUT1 was evaluated using confocal fluorescence microscopy imaging, flow cytometry assays and in vivo IVIS spectrum imaging. RESULTS: A dual-targeting fluorescent probe named NGF was successfully synthesized to bind to both NRP1 and GLUT1 receptors. NGF exhibited greater hydrophilicity (Log P = -0.95 ± 0.07) and superior optical properties compared to its precursor, G. Confocal fluorescence imaging, flow cytometry assays, and blocking studies revealed that the cellular uptake of NGF correlated with the NRP1 and GLUT1 expression levels across cell lines. Moreover, a strong linear relationship (R = 0.98) was observed between fluorescence intensity and increasing NGF concentrations in MDA-MB-231 cells. In vivo IVIS imaging in animal models demonstrated specific binding of NGF to breast cancer (MDA-MB-231) and colorectal cancer (HCT116), with prolonged retention observed up to 72 h. CONCLUSIONS: This study highlighted the efficient targeting and sustained retention of the dual-target heterodimeric fluorescent probe NGF, binding to NRP1 and GLUT1 receptors. These findings suggest significant potential for clinical applications in early cancer detection and fluorescence image-guided surgery.
Correction: Preclinical Development of Near-Infrared-Labeled CD38-Targeted Daratumumab for Optical Imaging of CD38 in Multiple Myeloma.
Cho N, Ko S, Shokeen M
Mol Imaging Biol · 2025 Jun · PMID 40042750 · Publisher ↗
Abstract loading — click title to view on PubMed.
Correction: Evaluation of [F]AlF NOTA-5G, an Aluminum [F]fluoride Labeled Peptide Targeting the Cell Surface Receptor Integrin Alpha(v)beta(6) for PET Imaging.
Hausner SH, Davis RA, Ganguly T … +2 more , Harris R, Sutcliffe JL
Mol Imaging Biol · 2025 Apr · PMID 40038219 · Publisher ↗
Abstract loading — click title to view on PubMed.
Spatial FAP Expression as Detected by Ga-FAPI-46 Identifies Myofibroblasts Beyond the Infarct Scar After Reperfusion.
Hess A, Renko A, Schäfer A … +9 more , Jung M, Fraccarollo D, Schmitto JD, Diekmann J, Thum T, Bengel FM, Bauersachs J, Thackeray JT, Tillmanns J
Mol Imaging Biol · 2025 Apr · PMID 40029570 · Full text
PURPOSE: Myocardial infarction (MI) triggers complex cellular responses essential for tissue repair and remodeling, including myofibroblast activation. Fibroblast activation protein alpha (FAP) identifies activated myofi...
PURPOSE: Myocardial infarction (MI) triggers complex cellular responses essential for tissue repair and remodeling, including myofibroblast activation. Fibroblast activation protein alpha (FAP) identifies activated myofibroblasts post-MI, however its spatial distribution relative to the scar and area at risk (AAR) is unclear. Non-invasive FAP-imaging with PET radiotracer Ga-FAPI-46 shows uptake beyond the infarct scar. We therefore aimed to characterize FAP expression in the AAR using a myocardial ischemia-reperfusion (MI/R) model in mice. PROCEDURES: We induced MI/R in male C57BL/6N mice. The AAR was identified by in vivo lectin staining, and expression of FAP, CD68, and hypoxic tissues were measured using immunohistochemistry. Spatial FAP was further interrogated by Ga-FAPI-46 in mice by autoradiography and humans by PET. Additionally, human cardiac tissues from acute MI patients were examined for fibroblasts and inflammatory cells by expression of FAP, CD13, and α-smooth muscle actin. RESULTS: FAP expression peaked three days post-MI/R predominantly within the AAR (p < 0.05 vs. d0). Consistent between murine models and human tissues, FAP myofibroblasts accumulated within the infarct scar and borderzone, occasionally extending into non-ischemic myocardium. CD68 macrophages peaked similarly at three days post-MI/R (p < 0.05 vs. d0). FAP expression weakly correlated with CD68 but not with extent of ischemic or hypoxic territory post-MI/R. FAP imaging in mice and humans revealed aligned non-uniform Ga-FAPI-46 uptake extending from the infarct scar into surviving myocardium after MI. CONCLUSIONS: Our findings demonstrate a distinct FAP expression pattern post-MI/R. The alignment of ex vivo Ga-FAPI-46 signal with myofibroblasts in the AAR supports its identification of a unique substrate in myocardial injury complementing other non-invasive imaging measurements of perfusion, viability and fibrosis.
Quantifying Molecular Changes in the Preeclamptic Rat Placenta with Targeted Contrast-Enhanced Ultrasound Imaging.
Shi L, Alencar AKN, Swan KF … +3 more , Lawrence DJ, Pridjian G, Bayer CL
Mol Imaging Biol · 2025 Apr · PMID 40014198 · Full text
PURPOSE: Abnormal placental remodeling is linked to various pregnancy-related diseases, including preeclampsia (PE). This study applies a bicompartmental (BCM) model to quantify molecular expression changes in the placen...
PURPOSE: Abnormal placental remodeling is linked to various pregnancy-related diseases, including preeclampsia (PE). This study applies a bicompartmental (BCM) model to quantify molecular expression changes in the placenta, indicative of abnormal placental remodeling, and evaluates the effectiveness of targeted contrast-enhanced ultrasound (T-CEUS) in detecting the abnormal placental vasculature. The BCM model provides high temporal resolution and differentiation of anatomical artery structures within the placenta by analyzing the distribution of contrast agents. METHODS: A targeted contrast agent (TCA) composed of gas-filled microbubbles (MB), with a surface-conjugated peptide to target αβ integrin, a biomarker for angiogenesis, was used for quantifying placental vascular development. CEUS images were acquired from timed pregnant Sprague Dawley rats with experimentally-induced reduced uterine perfusion pressure (RUPP) placental insufficiency. On gestational day (GD) 18 of a 21-day gestation, CEUS images were acquired from both Normal pregnant (NP; n = 6) and RUPP (n = 6) dams after injection of the TCA. The BCM model was used to estimate the binding dynamics of the TCA, providing a parametric map of the binding constant ( ) of the placenta. RESULTS: The RUPP group showed a significant reduction in the value of compared to the NP group (p < 0.05). A histogram of the placental was compared to alternative analyses (differential target enhancement, dTE and late enhancement, LE) to demonstrate that it can differentiate between anatomical artery structures with a higher contrast-to-background ratio. CONCLUSIONS: The BCM method differentiates molecular changes associated with the abnormal placental development associated with PE. It also reveals more intricate internal anatomical structures of the placenta in comparison to dTE and LE, suggesting that the BCM could enhance early detection and monitoring of PE.
Evaluation of [F]JNJ-CSF1R-1 as a Positron Emission Tomography Ligand Targeting Colony-Stimulating Factor 1 Receptor.
Salarian M, Liu S, Tsai HM … +11 more , Leslie SN, Hayes T, Lo ST, Szardenings AK, Zhang W, Chen G, Sandiego C, Wells L, Nair DG, Kolb HC, Xia CA
Mol Imaging Biol · 2025 Apr · PMID 40009327 · Publisher ↗
PURPOSE: Colony-stimulating factor 1 receptor (CSF1R) signaling plays a pivotal role in neuroinflammation, driving microglia proliferation and activation. CSF1R is considered a hallmark of inflammation in many neurodegen...
PURPOSE: Colony-stimulating factor 1 receptor (CSF1R) signaling plays a pivotal role in neuroinflammation, driving microglia proliferation and activation. CSF1R is considered a hallmark of inflammation in many neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Our study aims to evaluate the potential value of 5-cyano-N-(4-(4-(2-([F]fluoro)ethyl)piperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide ([F]JNJ-CSF1R-1) as a positron emission tomography (PET) ligand targeting CSF1R in preclinical models of neuroinflammation. PROCEDURES: A cell-based MSD assay was used to measure the IC of 5-cyano-N-(4-(4-(2-(fluoro)ethyl)piperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide (JNJ-CSF1R-1). JNJ-CSF1R-1 was radiolabeled with fluorine-18. PET imaging was used to evaluate brain uptake, and target engagement of [F]JNJ-CSF1R-1 in two neuroinflammation mouse models, including systemic lipopolysaccharide (LPS) and App knock in (KI). CSF1R protein levels in brain tissue were determined by western blot and ELISA assays. [F]JNJ-CSF1R-1 brain uptake was also measured in a non-human primate (NHP) PET study. RESULTS: JNJ-CSF1R-1 is a 12 nM (IC) inhibitor of CSF1R. [F]JNJ-CSF1R-1 demonstrated significantly higher brain uptake in both LPS and AD mouse models as measured by the area under the time activity curves (AUC) compared to control animals. In the App KI model, CSF1R levels increased near amyloid plaques as detected by IHC. [F]JNJ-CSF1R-1 PET imaging signal showed a good correlation with CSF1R expression levels measured by western blot and ELISA. In an NHP study, [F]JNJ-CSF1R-1 readily entered the brain and demonstrated reversible kinetics. CONCLUSION: [F]JNJ-CSF1R-1 is a potent and promising CSF1R PET tracer with translational potential for measuring microglia-based neuroinflammatory processes and for tracking the impact of anti-inflammatory therapies.
Evaluation of [F]AlF NOTA-5G, an Aluminum [F]fluoride Labeled Peptide Targeting the Cell Surface Receptor Integrin Alpha(v)beta(6) for PET Imaging.
Hausner SH, Davis RA, Ganguly T … +2 more , Harris R, Sutcliffe JL
Mol Imaging Biol · 2025 Apr · PMID 39979580 · Full text
PURPOSE: Peptide-based probes targeting integrin αβ have shown promise in clinical trials for cancer imaging based on the high over-expression of this epithelial-specific cell surface receptor in many cancerous tissues....
PURPOSE: Peptide-based probes targeting integrin αβ have shown promise in clinical trials for cancer imaging based on the high over-expression of this epithelial-specific cell surface receptor in many cancerous tissues. Recently, the αβ-targeting gallium-68 labeled DOTA-5G peptide, [Ga]Ga DOTA-5G, demonstrated diagnostic value in patients with metastatic pancreatic cancer. To facilitate adoption at sites without access to gallium-68 and take advantage of the characteristics of fluorine-18 through convenient [F]fluoride chelation chemistry, this study evaluated the fluorine-18 labeled analog, [F]AlF NOTA-5G, in vitro and in vivo in a tumor mouse model, and compared it to [Ga]Ga DOTA-5G. PROCEDURES: NOTA-5G was synthesized on solid phase and radiolabeled with aluminum [F]fluoride to generate [F]AlF NOTA-5G. Cell binding and internalization of [F]AlF NOTA-5G were evaluated in paired DX3puroβ6 (αβ +) and DX3puro (αβ -), and pancreatic BxPC-3 (αβ +) cells. Imaging (1-6 h) and biodistribution were performed in BxPC-3 tumor-bearing mice. RESULTS: [F]AlF NOTA-5G was obtained in > 93% radiochemical purity. Cell binding was αβ-targeted (1 h: 66% bound to DX3puroβ6, vs 2% to DX3puro), and ≥ 50% of bound activity was internalized; analogous to [Ga]Ga DOTA-5G, PET imaging showed clearly delineated tumors. Excretion remained primarily renal (1 to 4 h: 18.6 to 12.5% ID/g). Tumor uptake remained relatively steady (1 to 4 h: 2.3 ± 0.4 to 1.8 ± 0.6% ID/g - closely matching [Ga]Ga DOTA-5G with 2.6 ± 0.8 and 2.0 ± 0.6% ID/g at 1 and 2 h), resulting in tumor/pancreas, tumor/liver, and tumor/blood ratios of 18/1, 24/1, and 162/1, respectively (4 h); by comparison, for [Ga]Ga DOTA-5G the values were 21/1, 20/1, and 22/1 (2 h). CONCLUSIONS: [F]AlF NOTA-5G demonstrated selective αβ-targeting and tumor uptake similar to [Ga]Ga DOTA-5G. The tumor-to-background ratio resulted high-contrast PET images, with an extended imaging window compared to [Ga]Ga DOTA-5G. The synthesis of [F]AlF NOTA-5G is currently being optimized for clinical production.
Leveraging Radiomics and Hybrid Quantum-Classical Convolutional Networks for Non-Invasive Detection of Microsatellite Instability in Colorectal Cancer.
Buvaneswari T, Ramkumar M, Venkatesan P … +1 more , Kumar RS
Mol Imaging Biol · 2025 Apr · PMID 39979579 · Publisher ↗
PURPOSE: The goal of this study is to create a novel framework for identifying MSI status in colorectal cancer using advanced radiomics and deep learning strategies, aiming to enhance clinical decision-making and improve...
PURPOSE: The goal of this study is to create a novel framework for identifying MSI status in colorectal cancer using advanced radiomics and deep learning strategies, aiming to enhance clinical decision-making and improve patient outcomes in oncology. PROCEDURES: The study utilizes histopathological slide images from the NCT-CRC-HE-100 K and PAIP 2020 databases. Key procedures include self-attentive adversarial stain normalization for data standardization, tumor delineation via a Slimmable Transformer, and radiomics feature extraction using a hybrid quantum-classical neural network. RESULTS: The proposed system reaches 99% accuracy when identifying colorectal cancer MSI status. It shows the model is good at telling the difference between MSI and MSS tumors and can be used in real medical care for cancer. CONCLUSIONS: Our research shows that the new system improves colorectal cancer MSI status determination better than previous methods. Our optimized processing technology works better than other methods to divide and analyze tissue features making the system good for improving patient care decisions.
Test-retest Assessment of Biventricular Myocardial Oxidative Metabolism and Perfusion in Pulmonary Hypertension Patients Using C-acetate PET Imaging: A Pilot Study.
Ahmadi A, Klein R, Gao D … +8 more , Mielniczuk LM, Zelt JGE, Boczar KE, Beanlands RS, Bravo PE, Han Y, Di Carli MF, deKemp RA
Mol Imaging Biol · 2025 Apr · PMID 39939405 · Publisher ↗
PURPOSE: C-acetate PET is used to measure biventricular oxygen myocardial consumption rate (MVO) and myocardial blood flow (MBF) changes associated with right ventricular (RV) remodelling. We studied PET reproducibility...
PURPOSE: C-acetate PET is used to measure biventricular oxygen myocardial consumption rate (MVO) and myocardial blood flow (MBF) changes associated with right ventricular (RV) remodelling. We studied PET reproducibility and repeatability for such RV assessments. PROCEDURES: 10 pulmonary hypertension (PH) patients underwent C-acetate PET. Five of these patients also had a repeat scan after 26 ± 2 weeks. A one-tissue compartment model was used to measure the myocardial tissue-activity washout rate (k2 [1/min] for MVO estimation) and the blood-to-tissue activity flux (K1 [1/min] for MBF calculation). Values were measured by 2 blinded observers and analyzed by ANOVA and Bland-Altman tests. The interquartile ranges (IQR), within-subject coefficients of variation (wCV), and intraclass correlation coefficients (ICC) were reported. RESULTS: All patients had stable PH with the clinical assessments showed comparable biventricular function and size between baseline and follow-up. The k2-derived MVO and K1-derived MBF values were consistently higher in the LV than RV. The high inter- and intra-observer reproducibility (for biventricular MVO and MBF) was indicated by low IQR (≤ 7.6%) and wCV (≤ 8%) as well as high ICC (≥ 95%). The test-retest (baseline to follow-up) repeatability showed larger IQR (≤ 35.4%) and wCV (≤ 29%) but consistently high ICC (= 95%). CONCLUSIONS: MVO and MBF values measured in the RV of patients with PH were highly reproducible and repeatable. This can help inform the design of clinical research studies using serial C-acetate PET imaging to evaluate RV metabolism.
2024 World Molecular Imaging Congress Program.
Mol Imaging Biol · 2025 Jan · PMID 39920433 · Publisher ↗
Abstract loading — click title to view on PubMed.
Optical-magnetic Imaging for Optimizing Lymphodepletion-TIL Combination Therapy in Breast Cancer.
Li J, Guo L, Feng Y … +6 more , Li G, Sun H, Huang W, Tian J, Du Y, An Y
Mol Imaging Biol · 2025 Apr · PMID 39909989 · Publisher ↗
PURPOSE: Lymphodepletion before tumor-infiltrating lymphocytes (TIL) infusion can activate the immune system, enhance the release of homeostatic cytokines, and decrease the number of immunosuppressive cells. This process...
PURPOSE: Lymphodepletion before tumor-infiltrating lymphocytes (TIL) infusion can activate the immune system, enhance the release of homeostatic cytokines, and decrease the number of immunosuppressive cells. This process is crucial for improving the therapeutic efficacy of TIL therapy. However, the challenge of in vivo assessing TILs targeting tumors limits the optimization of lymphodepleting conditioning regimen (LDC). PROCEDURES: This study aims to employ magnetic particle imaging (MPI) and fluorescence molecular imaging (FMI) to monitor TIL biodistribution in vivo and optimize LDC in triple-negative breast cancer TIL therapy. MPI provides quantitative imaging capabilities without depth limitations, effectively complementing the high sensitivity of FMI. The efficacy of different LDCs in enhancing TIL therapy was assessed using FMI, and MPI quantified the number of TILs accumulated in the 4T1 tumor. RESULTS: TILs preserved viability, phenotypes, and anti-tumor efficacy after being labeled with superparamagnetic iron oxide and fluorescence dye DiR. The dual-modality imaging system effectively discerned variations in LDC treatments that enhanced TIL therapy. Compared to TIL monotherapy, lymphodepletion with TIL therapy improves tumor dual-modality imaging signal intensity, increases the expression of monocyte chemotactic protein-1 in serum and tumor tissue, and enhances the therapeutic effect of TILs. CONCLUSION: Our results confirm the utility of optical-magnetic dual-modality imaging for tracking the biodistribution of TILs in vivo. With the help of optical-magnetic dual-modality imaging, we successfully optimize TIL combination therapy. Optical-magnetic dual-modality imaging provides a new approach to develop personalized immunotherapy strategies and mine potential therapeutic mechanisms for TIL.
DCE-MRI Detects OATP-expressing Transplanted Cells Using Clinical Doses of Gadolinium Contrast Agent.
Bhattacharyya T, Mallett CL, Hix JM … +1 more , Shapiro EM
Mol Imaging Biol · 2025 Apr · PMID 39904956 · Publisher ↗
PURPOSE: Hepatic organic anion transporting polypeptides (OATPs) transport off-the-shelf, FDA-approved, hepatospecific Gd-based MRI contrast agents into cells that express the transporters enhancing signal on T1-weighted...
PURPOSE: Hepatic organic anion transporting polypeptides (OATPs) transport off-the-shelf, FDA-approved, hepatospecific Gd-based MRI contrast agents into cells that express the transporters enhancing signal on T1-weighted MRI. Studies have used MRI to identify OATP-overexpressing tumors and metastases transplanted in mice following the delivery of Gd-EOB-DTPA at 27-67-fold higher than clinical doses. With safety and regulatory concerns over Gd-based contrast agents, translating OATPs as an MRI reporter protein to humans for regenerative medicine will require substantially lower doses of agent. PROCEDURES: We engineered the MyC-CaP mouse tumor cell line to express rat OATP1B2, which influxes both Gd-EOB-DTPA and Gd-BOPTA, resulting in signal enhancement on T1-weighted MRI. We then inoculated mice with rat OATP1B2 and non-expressing cells bilaterally to generate tumors. 3-4 weeks after inoculation, when tumors had formed, in-vivo MRI imaging was performed with delivery of 0.025 mmol/kg or 0.25 mmol/kg of the Gd-based contrast agents. We complemented static T1-weighted MRI and T1-mapping with dynamic contrast enhanced (DCE)-MRI and performed area under the curve (AUC) analysis to discriminate the two tumor types. RESULTS: While all OATP1B2-expressing tumors were easily visible at the high dose of 0.25 mmol/kg on T1-weighted MRI and easy to distinguish from control tumors, OATP1B2-expressing tumors were hard to identify and distinguish from non-expressing tumors at the lower, clinical dose of 0.025 mmol/kg with standard T1-weighted MRI or T1-mapping. However, AUC analyses of the DCE-MRI curves could identify and distinguish these tumors, needing 30 (Gd-EOB-DTPA) or 45 (Gd-BOPTA) minutes acquisition time. CONCLUSIONS: By performing AUC analyses of DCE-MRI curves following delivery of clinical concentration of MRI contrast agents, OATP1B2-expressing tumors could be identified and distinguished from control tumors, suggesting this imaging approach as a path to substantially reducing the amount of contrast agent needed to use OATPs as a clinically viable reporter protein for imaging regenerative medicine.
Autoradiography of Intracerebral Tumours in the Chick Embryo Model: A Feasibility Study Using Different PET Tracers.
Krause S, Florea A, Choi CH … +10 more , Worthoff WA, Heinzel A, Fischer S, Burda N, Neumaier B, Shah NJ, Lohmann P, Mottaghy FM, Langen KJ, Stegmayr C
Mol Imaging Biol · 2025 Apr · PMID 39838234 · Full text
PURPOSE: In addition to rodent models, the chick embryo model has gained attention for radiotracer evaluation. Previous studies have investigated tumours on the chorioallantoic membrane (CAM), but its value for radiotrac...
PURPOSE: In addition to rodent models, the chick embryo model has gained attention for radiotracer evaluation. Previous studies have investigated tumours on the chorioallantoic membrane (CAM), but its value for radiotracer imaging of intracerebral tumours has yet to be demonstrated. PROCEDURES: Human U87 glioblastoma cells and U87-IDH1 mutant glioma cells were implanted into the brains of chick embryos at developmental day 5. After 12-14 days of tumour growth, blood-brain-barrier integrity was evaluated in vivo using MRI contrast enhancement or ex vivo with Evans blue dye. The tracers O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET) (n = 5), 3,4-dihydroxy-6-[F]-fluoro-L-phenylalanine ([F]FDOPA) (n = 3), or [Ga] labelled quinoline-based small molecule fibroblast activation protein inhibitor ([Ga]FAPI-46) (n = 4) were injected intravenously if solid tumours were detected with MRI. For time-activity curves for [F]FET, additional micro PET (µPET) was performed. The chick embryos were sacrificed 60 min post-injection, and cryosections of the tumour-bearing brains were produced and evaluated with autoradiography and immunohistochemistry. RESULTS: Intracerebral tumours were produced with a 100% success rate in viable chick embryos at the experimental endpoint. However, 52% of chick embryos (n = 85) did not survive the procedure to embryonic development day 20. For the evaluated radiotracers, the tumour-to-brain ratios (TBR) derived from ex vivo autoradiography, as well as the tracer kinetics derived from µPET for intracerebral chick embryo tumours, were comparable to those previously reported in rodents and patients: the TBRmean for [F]FET was 1.69 ± 0.54 (n = 5), and 3.8 for one hypermetabolic tumour and < 2.0 for two isometabolic tumors using [F]FDOPA, with a TBRmean of 1.92 ± 1,11 (n = 3). The TBRmean of [Ga]FAPI-46 for intracerebral chick embryo tumours was 19.13 ± 0.64 (n = 4). An intact blood-tumour barrier was observed in one U87-MG tumour (n = 5). CONCLUSIONS: Radiotracer imaging of intracerebral tumours in the chick embryo offers a fast model for the evaluation of radiotracer uptake, accumulation, and kinetics. Our results indicate a high comparability between intracerebral tumour imaging in chick embryos and xenograft rodent models or brain tumour patients.
PET Imaging of a Transgenic Tau Rat Model SHR24 with [F]AV1451.
Ramakrishnan NK, Zhao AZ, Thompson S … +5 more , Milicevic Sephton S, Williamson DJ, Smolek T, Žilka N, Aigbirhio FI
Mol Imaging Biol · 2025 Apr · PMID 39838233 · Full text
PURPOSE: Positron Emission Tomography (PET) scans with radioligands targeting tau neurofibrillary tangles (NFT) have accelerated our understanding of the role of misfolded tau in neurodegeneration. While intended for hum...
PURPOSE: Positron Emission Tomography (PET) scans with radioligands targeting tau neurofibrillary tangles (NFT) have accelerated our understanding of the role of misfolded tau in neurodegeneration. While intended for human research, applying these radioligands to small animals establishes a vital translational link. Transgenic animal models of dementia, such as the tau rat SHR24, play a crucial role in enhancing our understanding of these disorders. This study aims to evaluate the utility of SHR24 rat model for PET studies. PROCEDURES: Dynamic PET scans were conducted in male SHR24 rats and their wild-type SHR (SHRwt) littermates using [F]AV1451. Rapid blood sampling and metabolite analysis were performed to acquire input curves. Time activity curves were obtained from various brain regions over 60 min. Blood-based, 2-Tissue Compartment Model (2-TCM) and Logan graphical analysis were used to obtain kinetic modelling parameters. The ability of reference tissue models to predict the binding potential (BP) were assessed. Autoradiography studies were performed to corroborate the scan data. RESULTS: Total distribution volume (V) was the best predicted parameter which revealed significantly higher uptake of [F]AV1451 in the cortex (5.8 ± 1.1 vs 4.6 ± 0.7, P < 0.05) of SHR24 rats compared to SHRwt rats. Binding potential obtained from 2-TCM was variable, however BP from reference tissue models detected significantly higher binding in cortex (0.28 ± 0.07 vs 0.20 ± 0.04, P < 0.01 by SRTM) and brainstem (0.14 ± 0.04 vs 0.08 ± 0.02, P < 0.01, by SRTM). CONCLUSIONS: With the ability to detect binding of established radioligand [F]AV1451 in these rats, we have demonstrated the utility of this model for assessing aggregated tau neurobiology by PET, with reference tissue models providing potential for longitudinal studies.
Deep Radiogenomics Sequencing for Breast Tumor Gene-Phenotype Decoding Using Dynamic Contrast Magnetic Resonance Imaging.
Shiri I, Salimi Y, Mohammadi Kazaj P … +4 more , Bagherieh S, Amini M, Saberi Manesh A, Zaidi H
Mol Imaging Biol · 2025 Feb · PMID 39815134 · Full text
PURPOSE: We aim to perform radiogenomic profiling of breast cancer tumors using dynamic contrast magnetic resonance imaging (MRI) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth fac...
PURPOSE: We aim to perform radiogenomic profiling of breast cancer tumors using dynamic contrast magnetic resonance imaging (MRI) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) genes. METHODS: The dataset used in the current study consists of imaging data of 922 biopsy-confirmed invasive breast cancer patients with ER, PR, and HER2 gene mutation status. Breast MR images, including a T1-weighted pre-contrast sequence and three post-contrast sequences, were enrolled for analysis. All images were corrected using N4 bias correction algorithms. Based on all images and tumor masks, a bounding box of 128 × 128 × 68 was chosen to include all tumor regions. All networks were implemented in 3D fashion with input sizes of 128 × 128 × 68, and four images were input to each network for multi-channel analysis. Data were randomly split into train/validation (80%) and test set (20%) with stratification in class (patient-wise), and all metrics were reported in 20% of the untouched test dataset. RESULTS: For ER prediction, SEResNet50 achieved an AUC mean of 0.695 (CI95%: 0.610-0.775), a sensitivity of 0.564, and a specificity of 0.787. For PR prediction, ResNet34 achieved an AUC mean of 0.658 (95% CI: 0.573-0.741), a sensitivity of 0.593, and a specificity of 0.734. For HER2 prediction, SEResNext101 achieved an AUC mean of 0.698 (95% CI: 0.560-0.822), a sensitivity of 0.750, and a specificity of 0.625. CONCLUSION: The current study demonstrated the feasibility of imaging gene-phenotype decoding in breast tumors using MR images and deep learning algorithms with moderate performance.
2-[F]Fluoropropionic Acid PET Imaging of Doxorubicin-Induced Cardiotoxicity.
Azcona JA, Wacker AS, Lee CH … +7 more , Fung EK, Jeitner TM, Manzo OL, Di Lorenzo A, Babich JW, Amor-Coarasa A, Kelly JM
Mol Imaging Biol · 2025 Feb · PMID 39810069 · Full text
PURPOSE: Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention...
PURPOSE: Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA). Therefore, we explored the utility of 2-[F]fluoropropionic acid ([F]FPA), an SCFA analog, as an imaging biomarker of cardiac injury in mice exposed to doxorubicin. PROCEDURES: Cardiotoxicity and cardiac dysfunction were induced in mice by an 8-dose regimen of doxorubicin (cumulative dose 24 mg/kg) administered over 14 days. The effects of doxorubicin exposure were assessed by measurement of heart weights, left ventricular ejection fractions, and blood cardiac troponin levels. Whole body and cardiac [F]FPA uptakes were determined by PET and tissue gamma counting in the presence or absence of AZD3965, a pharmacological inhibitor of monocarboxylate transporter 1 (MCT1). Radiation absorbed doses were estimated using tissue time-activity concentrations. RESULTS: Significantly higher cardiac [F]FPA uptake was observed in doxorubicin-treated animals. This uptake remained constant from 30 to 120 min post-injection. Pharmacological inhibition of MCT1-mediated transport by AZD3965 selectively decreased the uptake of [F]FPA in tissues other than the heart. Co-administration of [F]FPA and AZD3965 enhanced the imaging contrast of the diseased heart while reducing overall exposure to radioactivity. CONCLUSIONS: [F]FPA, especially when co-administered with AZD3965, is a new tool for imaging changes in fatty acid metabolism occurring in response to doxorubicin-induced cardiomyopathy by PET.
Evaluation of Inflammatory Activity of Extraocular Muscles in Thyroid Associated Orbitopathy by [Ga]DOTATATE PET/CT.
Hu Z, Liu J, Deng H … +6 more , Chen N, Chen L, Wang S, Long T, Tan J, Hu S
Mol Imaging Biol · 2025 Feb · PMID 39810068 · Publisher ↗
PURPOSE: The accurate assessment of inflammatory activity of the extraocular muscles (EOMs) in thyroid associated ophthalmopathy (TAO) is crucial for formulating subsequent treatment strategies and prognostic judgments....
PURPOSE: The accurate assessment of inflammatory activity of the extraocular muscles (EOMs) in thyroid associated ophthalmopathy (TAO) is crucial for formulating subsequent treatment strategies and prognostic judgments. This study aims to explore the efficacy of using [Ga]DOTATATE PET/CT to assess the inflammatory activity of EOMs in TAO patients. PROCEDURES: This study enrolled 22 TAO patients and 6 healthy volunteers, all of whom underwent orbital [Ga]DOTATATE PET/CT. Among these, 18 patients underwent orbital [Tc]DTPA SPECT/CT within one week, and the other 4 patients received orbital MRI. All imaging data were independently assessed, followed by comparative data analysis. The patients then received different treatment schemes, and their prognosis was followed up. RESULTS: [Ga]DOTATATE PET/CT could effectively evaluate the inflammatory activity of the EOMs in TAO patients and demonstrate good consistency with [Tc]DTPA SPECT/CT and orbital MRI, but show a better resolution to distinguish EOMs and surrounding structure. The receiver operating characteristic (ROC) curves for each EOM, treated as individual research units, exhibited an area under the curve (AUC) exceeding 0.9. The medial rectus demonstrated the highest involvement and diagnostic accuracy(AUC = 0.976, P < 0.001). Patients treated with glucocorticoids showed significantly higher SUVmax in EOMs compared to those receiving symptomatic treatment (P < 0.01). CONCLUSIONS: [Ga]DOTATATE PET/CT is a reliable method for assessing the inflammatory activity of EOMs in TAO patients, providing strong objective evidence for the precise diagnosis and treatment.
Oral Administration of [F]MC225 for Quantification of P-glycoprotein Function: A Feasibility Study.
Salvi de Souza G, Furini CRG, Sijbesma JWA … +6 more , Kominia M, Doorduin J, Giacobbo BL, Lammertsma AA, Tsoumpas C, Luurtsema G
Mol Imaging Biol · 2025 Feb · PMID 39810067 · Full text
PURPOSE: This preclinical study explored the feasibility of assessing P-glycoprotein (P-gp) function in both brain and gastrointestinal (GI) tract of rats using positron emission tomography (PET) following oral administr...
PURPOSE: This preclinical study explored the feasibility of assessing P-glycoprotein (P-gp) function in both brain and gastrointestinal (GI) tract of rats using positron emission tomography (PET) following oral administration of [F]MC225. Different oral administration protocols were evaluated, and radioactivity uptake was compared with uptake following intravenous administration. PROCEDURES: Twelve male Wistar rats were divided into four groups and subjected to intravenous or oral [F]MC225 administration protocols: G (intravenous route), G (oral administration without fasting), G (oral administration with fasting), and G (oral administration with fasting following administration of the P-gp inhibitor tariquidar). Dynamic brain imaging, late abdominal imaging, ex vivo biodistribution, and metabolite analysis were conducted to assess tracer distribution. RESULTS: In the brain, oral administration yielded lower values compared with intravenous administration, resulting in a reduction in the tissue-to-plasma ratio by approximately 51% for the cortex and 45% for the midbrain and cerebellum. Fasting improved radioactivity uptake, aiding brain visualization. Unexpectedly, administration of the P-gp inhibitor tariquidar did not increase brain concentration, suggesting a signal that was dominated by non-specific uptake, possibly due to instability of [F]MC225 in the GI tract. Metabolite analysis in G indicated a significant presence of polar metabolites. CONCLUSIONS: Oral administration of [F]MC225 faces challenges and, at this stage, cannot be used to quantify P-gp function. Further research to assess tracer stability and metabolism in the stomach and intestine will be essential for advancing the feasibility of oral tracer administration.
F-FAPI-42 PET/CT and F-FDG PET/CT in Patients with Malignant Digestive System Neoplasms: A Head-to-Head Comparative Study.
Xiong M, You H, Feng J … +4 more , Liu Y, Luo X, Liu Y, Jiang SN
Mol Imaging Biol · 2025 Feb · PMID 39806262 · Publisher ↗
PURPOSE: Radionuclide-labeled fibroblast activation protein inhibitor (FAPI) is an emerging tumor tracer. We sought to assess the uptake and diagnostic performance of F-FAPI-42 PET/CT compared with simultaneous 2-deoxy-2...
PURPOSE: Radionuclide-labeled fibroblast activation protein inhibitor (FAPI) is an emerging tumor tracer. We sought to assess the uptake and diagnostic performance of F-FAPI-42 PET/CT compared with simultaneous 2-deoxy-2[F]fluoro-D-glucose (F-FDG) PET/CT in primary and metastatic lesions in patients with malignant digestive system neoplasms and to determine the potential clinical benefit. PROCEDURES: Forty-two patients (men = 30, women = 12, mean age = 56.71 ± 13.26 years) who underwent F-FDG PET/CT and F-FAPI-42 PET/CT simultaneously for diagnosis, staging, and restaging were enrolled. Quantitative data, including standardized uptake value (SUV), tumor-to-liver ratio (TLR), and tumor-to-blood pool ratio (TBR), were analyzed. Two independent readers performed a visual assessment of lesion number and location on PET/CT images. Interobserver agreement between two examinations was calculated using Cohen's kappa (κ). RESULTS: Primary tumor locations included the liver (n = 20), stomach (n = 9), pancreas (n = 5), and intestine (n = 10). More intense F-FAPI-42 uptake and higher tumor-to-background contrast were detected in most primary and metastatic lesions compared with F-FDG, contributing to improved diagnostic accuracy ranging from 95.24% to 100%. Moreover, additional lesions showing F-FAPI-42 uptake in primary, locoregional and distant metastatic lesions were visualized, especially in multiple liver and peritoneal metastases. Patient-based interobserver agreement varied from moderate to strong, with suboptimal outcomes observed in primary tumors (κ = 0.441, P = 0.01) and preferable results derived from metastatic liver and bone lesions (κ = 1 and 0.896, both P < 0.01). F-FAPI-42 PET/CT resulted in modified treatment strategies for 40.48% (17/42) of patients, while F-FDG PET/CT led to altered therapeutic regimens in only 4.8% (2/42) of patients. CONCLUSIONS: In selected patients with malignant digestive system neoplasms, our study shows that F-FAPI-42 PET/CT is a promising alternative for assessing primary tumors and metastases and aiding staging, restaging, and decision-making, with higher uptake and better lesion visualization compared with F-FDG. Additionally, it may shed light into the treatment selection and response assessment for FAP-targeted therapy or immunotherapy.
PET Imaging of Sphingosine-1-Phosphate Receptor 1 with [F]TZ4877 in Nonhuman Primates.
Gu J, Zheng MQ, Holden D … +10 more , Fowles K, Qiu L, Felchner Z, Zhang L, Ropchan J, Gropler RJ, Carson RE, Tu Z, Huang Y, Hillmer AT
Mol Imaging Biol · 2025 Feb · PMID 39779653 · Full text
PURPOSE: The sphingosine-1-phosphate receptor-1 (S1PR) is involved in regulating responses to neuroimmune stimuli. There is a need for S1PR-specific radioligands with clinically suitable brain pharmcokinetic properties t...
PURPOSE: The sphingosine-1-phosphate receptor-1 (S1PR) is involved in regulating responses to neuroimmune stimuli. There is a need for S1PR-specific radioligands with clinically suitable brain pharmcokinetic properties to complement existing radiotracers. This work evaluated a promising S1PR radiotracer, [F]TZ4877, in nonhuman primates. PROCEDURES: [F]TZ4877 was produced via nucleophilic substitution of tosylate precursor with K[F]/F followed by deprotection. Brain PET imaging data were acquired with a Focus220 scanner in two Macaca mulatta (6, 13 years old) for 120-180 min following bolus injection of 118-163 MBq [F]TZ4877, with arterial blood sampling and metabolite analysis to measure the parent input function and plasma free fraction (f). Each animal was scanned at baseline, 15-18 min after 0.047-0.063 mg/kg of the S1PR inhibitor ponesimod, 33 min after 0.4-0.8 mg/kg of the S1PR-specific compound TZ82112, and 167-195 min after 1 ng/kg of the immune stimulus endotoxin. Kinetic analysis with metabolite-corrected input function was performed to estimate the free fraction corrected total distribution volume (V/f). Whole-body dosimetry scans were acquired in 2 animals (1M, 1F) with a Biograph Vision PET/CT System, and absorbed radiation dose estimates were calculated with OLINDA. RESULTS: [F]TZ4877 exhibited fast kinetics that were described by the reversible 2-tissue compartment model. Baseline [F]TZ4877 f was low (<1%), and [F]TZ4877 V/f values were 233-866 mL/cm. TZ82112 dose-dependently reduced [F]TZ4877 V/f, while ponesimod and endotoxin exhibited negligible effects on V/f, possibly due to scan timing relative to dosing. Dosimetry studies identified the critical organs of gallbladder (0.42 (M) and 0.31 (F) mSv/MBq) for anesthetized nonhuman primate. CONCLUSIONS: [F]TZ4877 exhibits reversible kinetic properties, but the low f value limits reproducible quantification with this radiotracer. S1PR is a compelling PET imaging target, and these data support pursuing alternative F-18 labeled radiotracers for potential future human studies.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe