Molecular Imaging and Biology最新文献

{"title":"Pilot Evaluation of S-(3-[¹⁸F]Fluoropropyl)-D-Homocysteine and O-(2-[¹⁸F]Fluoroethyl)-D-Tyrosine as Bacteria-Specific Radiotracers for PET Imaging of Infection.","authors":"Helen M Betts, Jeni C Luckett, Philip J Hill","doi":"10.1007/s11307-024-01929-7","DOIUrl":"10.1007/s11307-024-01929-7","url":null,"abstract":"<p><strong>Purpose: </strong>There is currently no ideal radiotracer for imaging bacterial infections. Radiolabelled D-amino acids are promising candidates because they are actively incorporated into the peptidoglycan of the bacterial cell wall, a structural feature which is absent in human cells. This work describes fluorine-18 labelled analogues of D-tyrosine and D-methionine, O-(2-[¹⁸F]fluoroethyl)-D-tyrosine (D-[¹⁸F]FET) and S-(3-[¹⁸F]fluoropropyl)-D-homocysteine (D-[¹⁸F]FPHCys), and their pilot evaluation studies as potential radiotracers for imaging bacterial infection.</p><p><strong>Procedures: </strong>D-[¹⁸F]FET and D-[¹⁸F]FPHCys were prepared in classical fluorination-deprotection reactions, and their uptake in Staphylococcus aureus and Pseudomonas aeruginosa was evaluated over 2 h. Heat killed bacteria were used as controls. A clinically-relevant foreign body model of S. aureus infection was established in Balb/c mice, as well as a sterile foreign body to mimic inflammation. The ex vivo biodistribution of D-[¹⁸F]FPHCys in the infected and inflamed mice was evaluated after 1 h, by dissection and gamma counting. The uptake was compared to that of [¹⁸F]FDG.</p><p><strong>Results: </strong>In vitro uptake of both D-[¹⁸F]FET and D-[¹⁸F]FPHCys was specific to live bacteria. Uptake was higher in S. aureus than in P. aeruginosa for both radiotracers, and of the two, higher for D-[¹⁸F]FPHCys than D-[¹⁸F]FET. Blocking experiments with non-radioactive D-[¹⁹F]FPHCys confirmed specificity of uptake. In vivo, D-[¹⁸F]FPHCys had greater accumulation in S. aureus infection compared with sterile inflammation, which was statistically significant. As anticipated, [¹⁸F]FDG showed no significant difference in uptake between infection and inflammation.</p><p><strong>Conclusions: </strong>D-[¹⁸F]FPHCys uptake was higher in infected tissues than inflammation, and represents a fluorine-18 labelled D-AA with potential to detect a S. aureus reference strain (Xen29) in vivo. Additional studies are needed to evaluate uptake of this radiotracer in clinical isolates.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"704-713"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate Specific Membrane Antigen Expression in a Syngeneic Breast Cancer Mouse Model.","authors":"Aditi A Shirke, Jing Wang, Gopolakrishnan Ramamurthy, Arpan Mahanty, Ethan Walker, Lifang Zhang, Abhiram Panigrahi, Xinning Wang, James P Basilion","doi":"10.1007/s11307-024-01920-2","DOIUrl":"10.1007/s11307-024-01920-2","url":null,"abstract":"<p><strong>Purpose: </strong>Prostate specific membrane antigen (PSMA) has been studied in human breast cancer (BCa) biopsies, however, lack of data on PSMA expression in mouse models impedes development of PSMA-targeted therapies, particularly in improving breast conserving surgery (BCS) margins. This study aimed to validate and characterize the expression of PSMA in murine BCa models, demonstrating that PSMA can be utilized to improve therapies and imaging techniques.</p><p><strong>Methods: </strong>Murine triple negative breast cancer 4T1 cells, and human cell lines, MDA-MB-231, MDA-MB-468, implanted into the mammary fat pads of BALB/c mice, were imaged by our PSMA targeted theranostic agent, PSMA-1-Pc413, and tumor to background ratios (TBR) were calculated to validate selective uptake. Immunohistochemistry was used to correlate PSMA expression in relation to CD31, an endothelial cell biomarker highlighting neovasculature. PSMA expression was also quantified by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).</p><p><strong>Results: </strong>Accumulation of PSMA-1-Pc413 was observed in 4T1 primary tumors and associated metastases. Average TBR of 4T1 tumors were calculated to be greater than 1.5-ratio at which tumor tissues can be distinguished from normal structures-at peak accumulation with the signal intensity in 4T1 tumors comparable to that in high PSMA expressing PC3-pip tumors. Extraction of 4T1 tumors and lung metastases followed by RT-PCR analysis and PSMA-CD31 co-staining shows that PSMA is consistently localized on tumor neovasculature with no expression in tumor cells and surrounding normal tissues.</p><p><strong>Conclusion: </strong>The selective uptake of PSMA-1-Pc413 in these cancer tissues as well as the characterization and validation of PSMA expression on neovasculature in this syngeneic 4T1 model emphasizes their potential for advancements in targeted therapies and imaging techniques for BCa. PSMA holds great promise as an oncogenic target for BCa and its associated metastases.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"714-728"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of New CD38 Targeted Peptides for Cancer Imaging.","authors":"Alexander Zheleznyak, Rui Tang, Kathleen Duncan, Brad Manion, Kexian Liang, Baogang Xu, Alexander Vanover, Anchal Ghai, Julie Prior, Stephen Lees, Samuel Achilefu, Kimberly Kelly, Monica Shokeen","doi":"10.1007/s11307-024-01901-5","DOIUrl":"10.1007/s11307-024-01901-5","url":null,"abstract":"<p><strong>Purpose: </strong>Multiple myeloma (MM) affects over 35,000 patients each year in the US. There remains a need for versatile Positron Emission Tomography (PET) tracers for the detection, accurate staging, and monitoring of treatment response of MM that have optimal specificity and translational attributes. CD38 is uniformly overexpressed in MM and thus represents an ideal target to develop CD38-targeted small molecule PET radiopharmaceuticals to address these challenges.</p><p><strong>Procedures: </strong>Using phage display peptide libraries and pioneering algorithms, we identified novel CD38 specific peptides. Imaging bioconjugates were synthesized using solid phase peptide chemistry, and systematically analyzed in vitro and in vivo in relevant MM systems.</p><p><strong>Results: </strong>The CD38-targeted bioconjugates were radiolabeled with copper-64 (⁶⁴Cu) with100% radiochemical purity and an average specific activity of 3.3 - 6.6 MBq/nmol. The analog NODAGA-PEG4-SL022-GGS (SL022: Thr-His-Tyr-Pro-Ile-Val-Ile) had a K_d of 7.55 ± 0.291 nM and was chosen as the lead candidate. ⁶⁴Cu-NODAGA-PEG4-SL022-GGS demonstrated high binding affinity to CD38 expressing human myeloma MM.1S-CBR-GFP-WT cells, which was blocked by the non-radiolabeled version of the peptide analog and anti-CD38 clinical antibodies, daratumumab and isatuximab, by 58%, 73%, and 78%, respectively. The CD38 positive MM.1S-CBR-GFP-WT cells had > 68% enhanced cellular binding when compared to MM.1S-CBR-GFP-KO cells devoid of CD38. Furthermore, our new CD38-targeted radiopharmaceutical allowed visualization of tumors located in marrow rich bones, remaining there for up to 4 h. Clearance from non-target organs occurred within 60 min. Quantitative PET data from a murine disseminated tumor model showed significantly higher accumulation in the bones of tumor-bearing animals compared to tumor-naïve animals (SUV_max 2.06 ± 0.4 versus 1.24 ± 0.4, P = 0.02). Independently, tumor uptake of the target compound was significantly higher (P = 0.003) compared to the scrambled peptide, ⁶⁴Cu-NODAGA-PEG4-SL041-GGS (SL041: Thr-Tyr-His-Ile-Pro-Ile-Val). The subcutaneous MM model demonstrated significantly higher accumulation in tumors compared to muscle at 1 and 4 h after tracer administration (SUV_max 0.8 ± 0.2 and 0.14 ± 0.04, P = 0.04 at 1 h; SUV_max 0.89 ± 0.01 and 0.09 ± 0.01, P = 0.0002 at 4 h).</p><p><strong>Conclusions: </strong>The novel CD38-targeted, radiolabeled bioconjugates were specific and allowed visualization of MM, providing a starting point for the clinical translation of such tracers for the detection of MM.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"738-752"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid Molecular and Functional Micro-CT Imaging Reveals Increased Myocardial Apoptosis Preceding Cardiac Failure in Progeroid Ercc1 Mice.","authors":"Bibi S van Thiel, Martine de Boer, Yanto Ridwan, Marion G J de Kleijnen, Nicole van Vliet, Janette van der Linden, Isa de Beer, Paula M van Heijningen, Wilbert P Vermeij, Jan H J Hoeijmakers, A H Jan Danser, Roland Kanaar, Dirk J Duncker, Ingrid van der Pluijm, Jeroen Essers","doi":"10.1007/s11307-024-01902-4","DOIUrl":"10.1007/s11307-024-01902-4","url":null,"abstract":"<p><strong>Purpose: </strong>In this study, we explored the role of apoptosis as a potential biomarker for cardiac failure using functional micro-CT and fluorescence molecular tomography (FMT) imaging techniques in Ercc1 mutant mice. Ercc1 is involved in multiple DNA repair pathways, and its mutations contribute to accelerated aging phenotypes in both humans and mice, due to the accumulation of DNA lesions that impair vital DNA functions. We previously found that systemic mutations and cardiomyocyte-restricted deletion of Ercc1 in mice results in left ventricular (LV) dysfunction at older age.</p><p><strong>Procedures and results: </strong>Here we report that combined functional micro-CT and FMT imaging allowed us to detect apoptosis in systemic Ercc1 mutant mice prior to the development of overt LV dysfunction, suggesting its potential as an early indicator and contributing factor of cardiac impairment. The detection of apoptosis in vivo was feasible as early as 12 weeks of age, even when global LV function appeared normal, underscoring the potential of apoptosis as an early predictor of LV dysfunction, which subsequently manifested at 24 weeks.</p><p><strong>Conclusions: </strong>This study highlights the utility of combined functional micro-CT and FMT imaging in assessing cardiac function and detecting apoptosis, providing valuable insights into the potential of apoptosis as an early biomarker for cardiac failure.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"628-637"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards Characterization of Skin Melanoma in the Clinic by Electron Paramagnetic Resonance (EPR) Spectroscopy and Imaging of Melanin.","authors":"Mohammad Wehbi, Evelyne Harkemanne, Lionel Mignion, Nicolas Joudiou, Isabelle Tromme, Jean-François Baurain, Bernard Gallez","doi":"10.1007/s11307-023-01836-3","DOIUrl":"10.1007/s11307-023-01836-3","url":null,"abstract":"<p><p>The incidence of melanoma is continuously increasing over time. Melanoma is the most aggressive skin cancer, significantly reducing quality of life and survival rates of patients at advanced stages. Therefore, early diagnosis remains the key to change the prognosis of patients with melanoma. In this context, advanced technologies are under evaluation to increase the accuracy of the diagnostic, to better characterize the lesions and visualize their possible invasiveness in the epidermis. Among the innovative methods, because melanin is paramagnetic, clinical low frequency electron paramagnetic resonance (EPR) that characterizes the melanin content in the lesion has the potential to be an adjunct diagnostic method of melanoma. In this review, we first summarize the challenges faced by dermatologists and oncologists in melanoma diagnostic and management. We also provide a historical perspective on melanin detection with a focus on EPR spectroscopy/imaging of melanomas. We describe key elements that allow EPR to move from in vitro studies to in vivo and finally to patients for melanoma studies. Finally, we provide a critical view on challenges to meet to make EPR operational in the clinic to characterize pigmented lesions.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"382-390"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9696924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluations of an Early Change in Tumor Pathophysiology in Response to Radiotherapy with Oxygen Enhanced Electron Paramagnetic Resonance Imaging (OE EPRI).","authors":"Tianzhe Li, Grace A Murley, Xiaofei Liang, Renee L Chin, Jorge de la Cerda, F William Schuler, Mark D Pagel","doi":"10.1007/s11307-024-01925-x","DOIUrl":"10.1007/s11307-024-01925-x","url":null,"abstract":"<p><strong>Purpose: </strong>Electron Paramagnetic Resonance Imaging (EPRI) can image the partial pressure of oxygen (pO₂) within in vivo tumor models. We sought to develop Oxygen Enhanced (OE) EPRI that measures tumor pO₂ with breathing gases of 21% O₂ (pO₂^21%) and 100% O₂ (pO₂^100%), and the differences in pO₂ between breathing gases (ΔpO₂). We applied OE EPRI to study the early change in tumor pathophysiology in response to radiotherapy in two tumor models of pancreatic cancer.</p><p><strong>Procedures: </strong>We developed a protocol that intraperitoneally administered OX071, a trityl radical contrast agent, and then acquired anatomical MR images to localize the tumor. Subsequently, we acquired two pO₂^21% and two pO₂^100% maps using the T1 relaxation time of OX071 measured with EPRI and a R₁-pO₂ calibration of OX071. We studied 4T1 flank tumor model to evaluate the repeatability of OE EPRI. We then applied OE EPRI to study COLO 357 and Su.86.86 flank tumor models treated with 10 Gy radiotherapy.</p><p><strong>Results: </strong>The repeatability of mean pO₂ for individual tumors was ± 2.6 Torr between successive scans when breathing 21% O₂ or 100% O₂, representing a precision of 9.6%. Tumor pO₂^21% and pO₂^100% decreased after radiotherapy for both models, although the decreases were not significant or only moderately significant, and the effect sizes were modest. For comparison, ΔpO₂ showed a large, highly significant decrease after radiotherapy, and the effect size was large. MANOVA and analyses of the HF10 hypoxia fraction provided similar results.</p><p><strong>Conclusions: </strong>EPRI can evaluate tumor pO₂ with outstanding precision relative to other imaging modalities. The change in ΔpO₂ before vs. after treatment was the best parameter for measuring the early change in tumor pathophysiology in response to radiotherapy. Our studies have established ΔpO₂ from OE EPRI as a new parameter, and have established that OE EPRI is a valuable new methodology for molecular imaging.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"448-458"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Electron Paramagnetic Resonance (EPR) to Evaluate Redox Status in a Preclinical Model of Acute Lung Injury.","authors":"Hanan B Elajaili, Nathan M Dee, Sergey I Dikalov, Joseph P Y Kao, Eva S Nozik","doi":"10.1007/s11307-023-01826-5","DOIUrl":"10.1007/s11307-023-01826-5","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with hyper- vs. hypo-inflammatory subphenotypes of acute respiratory distress syndrome (ARDS) exhibit different clinical outcomes. Inflammation increases the production of reactive oxygen species (ROS) and increased ROS contributes to the severity of illness. Our long-term goal is to develop electron paramagnetic resonance (EPR) imaging of lungs in vivo to precisely measure superoxide production in ARDS in real time. As a first step, this requires the development of in vivo EPR methods for quantifying superoxide generation in the lung during injury, and testing if such superoxide measurements can differentiate between susceptible and protected mouse strains.</p><p><strong>Procedures: </strong>In WT mice, mice lacking total body extracellular superoxide dismutase (EC-SOD) (KO), or mice overexpressing lung EC-SOD (Tg), lung injury was induced with intraperitoneal (IP) lipopolysaccharide (LPS) (10 mg/kg). At 24 h after LPS treatment, mice were injected with the cyclic hydroxylamines 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine hydrochloride (CPH) or 4-acetoxymethoxycarbonyl-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-3-carboxylic acid (DCP-AM-H) probes to detect, respectively, cellular and mitochondrial ROS - specifically superoxide. Several probe delivery strategies were tested. Lung tissue was collected up to one hour after probe administration and assayed by EPR.</p><p><strong>Results: </strong>As measured by X-band EPR, cellular and mitochondrial superoxide increased in the lungs of LPS-treated mice compared to control. Lung cellular superoxide was increased in EC-SOD KO mice and decreased in EC-SOD Tg mice compared to WT. We also validated an intratracheal (IT) delivery method, which enhanced the lung signal for both spin probes compared to IP administration.</p><p><strong>Conclusions: </strong>We have developed protocols for delivering EPR spin probes in vivo, allowing detection of cellular and mitochondrial superoxide in lung injury by EPR. Superoxide measurements by EPR could differentiate mice with and without lung injury, as well as mouse strains with different disease susceptibilities. We expect these protocols to capture real-time superoxide production and enable evaluation of lung EPR imaging as a potential clinical tool for subphenotyping ARDS patients based on redox status.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"495-502"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9857422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulse and CW EPR Oximetry Using Oxychip in Gemcitabine-Treated Murine Pancreatic Tumors.","authors":"Gabriela Dziurman, Agnieszka Drzał, Aleksandra Anna Murzyn, Maciej Mikolaj Kmiec, Martyna Elas, Martyna Krzykawska-Serda","doi":"10.1007/s11307-023-01859-w","DOIUrl":"10.1007/s11307-023-01859-w","url":null,"abstract":"<p><strong>Purpose: </strong>The goal of this work was to compare pO₂ measured using both continuous wave (CW) and pulse electron paramagnetic resonance (EPR) spectroscopy. The Oxychip particle spin probe enabled longitudinal monitoring of pO₂ in murine pancreatic tumor treated with gemcitabine during the course of therapy.</p><p><strong>Procedures: </strong>Pancreatic PanO2 tumors were growing in the syngeneic mice, in the leg. Five doses of saline in control animals or gemcitabine were administered every 3 days, and pO₂ was measured after each dose at several time points. Oxygen partial pressure was determined from the linewidth of the CW EPR signal (Bruker E540L) or from the T₂ measured using the electron spin echo sequence (Jiva-25™).</p><p><strong>Results: </strong>The oxygen sensitivity was determined from a calibration curve as 6.1 mG/mm Hg in CW EPR and 68.5 ms^-1/mm Hg in pulse EPR. A slight increase in pO₂ of up to 20 mm Hg was observed after the third dose of gemcitabine compared to the control. The maximum delta pO₂ during the therapy correlated with better survival.</p><p><strong>Conclusions: </strong>Both techniques offer fast and reliable oximetry in vivo, allowing to follow the effects of pharmaceutic intervention.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"473-483"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward a Nanoencapsulated EPR Imaging Agent for Clinical Use.","authors":"Rhia M Martin, Samantha Diaz, Martin Poncelet, Benoit Driesschaert, Eugene Barth, Mrignayani Kotecha, Boris Epel, Gareth R Eaton, Joshua R Biller","doi":"10.1007/s11307-023-01863-0","DOIUrl":"10.1007/s11307-023-01863-0","url":null,"abstract":"<p><strong>Purpose: </strong>Progress toward developing a novel radiocontrast agent for determining pO₂ in tumors in a clinical setting is described. The imaging agent is designed for use with electron paramagnetic resonance imaging (EPRI), in which the collision of a paramagnetic probe molecule with molecular oxygen causes a spectroscopic change which can be calibrated to give the real oxygen concentration in the tumor tissue.</p><p><strong>Procedures: </strong>The imaging agent is based on a nanoscaffold of aluminum hydroxide (boehmite) with sizes from 100 to 200 nm, paramagnetic probe molecule, and encapsulation with a gas permeable, thin (10-20 nm) polymer layer to separate the imaging agent and body environment while still allowing O₂ to interact with the paramagnetic probe. A specially designed deuterated Finland trityl (dFT) is covalently attached on the surface of the nanoparticle through 1,3-dipolar addition of the alkyne on the dFT with an azide on the surface of the nanoscaffold. This click-chemistry reaction affords 100% efficiency of the trityl attachment as followed by the complete disappearance of the azide peak in the infrared spectrum. The fully encapsulated, dFT-functionalized nanoparticle is referred to as RADI-Sense.</p><p><strong>Results: </strong>Side-by-side in vivo imaging comparisons made in a mouse model made between RADI-Sense and free paramagnetic probe (OX-071) showed oxygen sensitivity is retained and RADI-Sense can create 3D pO₂ maps of solid tumors CONCLUSIONS: A novel encapsulated nanoparticle EPR imaging agent has been described which could be used in the future to bring EPR imaging for guidance of radiotherapy into clinical reality.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"525-541"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vivo Electron Paramagnetic Resonance Molecular Profiling of Tumor Microenvironment upon Tumor Progression to Malignancy in an Animal Model of Breast Cancer.","authors":"Timothy D Eubank, Andrey A Bobko, E Hannah Hoblitzell, Marieta Gencheva, Benoit Driesschaert, Valery V Khramtsov","doi":"10.1007/s11307-023-01847-0","DOIUrl":"10.1007/s11307-023-01847-0","url":null,"abstract":"<p><strong>Purpose: </strong>Hypoxia and acidosis are recognized tumor microenvironment (TME) biomarkers of cancer progression. Alterations in cancer redox status and metabolism are also associated with elevated levels of intracellular glutathione (GSH) and interstitial inorganic phosphate (Pi). This study aims to evaluate the capability of these biomarkers to discriminate between stages and inform on a switch to malignancy.</p><p><strong>Procedures: </strong>These studies were performed using MMTV-PyMT( +) female transgenic mice that spontaneously develop breast cancer and emulate human tumor staging. In vivo assessment of oxygen concentration (pO₂), extracellular acidity (pH_e), Pi, and GSH was performed using L-band electron paramagnetic resonance spectroscopy and multifunctional trityl and GSH-sensitive nitroxide probes.</p><p><strong>Results: </strong>Profiling of the TME showed significant deviation of measured biomarkers upon tumor progression from pre-malignancy (pre-S4) to the malignant stage (S4). For the combined marker, HOP: (pH_e × pO₂)/Pi, a value > 186 indicated that the tumors were pre-malignant in 85% of the mammary glands analyzed, and when < 186, they were malignant 42% of the time. For GSH, a value < 3 mM indicated that the tumors were pre-malignant 74% of the time, and when > 3 mM, they were malignant 80% of the time. The only marker that markedly deviated as early as stage 1 (S1) from its value in pre-S1 was elevated Pi, followed by a decrease of pH_e and pO₂ and increase in GSH at later stages.</p><p><strong>Conclusion: </strong>Molecular TME profiling informs on alteration of tumor redox and metabolism during tumor staging. Early elevation of interstitial Pi at S1 may reflect tumor metabolic alterations that demand elevated phosphorus supply in accordance with the high rate growth hypothesis. These metabolic changes are supported by the following decrease of pH_e due to a high tumor reliance on glycolysis and increase of intracellular GSH, a major intracellular redox buffer. The appreciable decrease in TME pO₂ was observed only at malignant S4, apparently as a consequence of tumor mass growth and corresponding decrease in perfusion efficacy and increase in oxygen consumption as the tumor cells proliferate.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"424-434"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}