Molecular Imaging and Biology最新文献

{"title":"Tumor Pre-Targeting System Using Streptavidin-Expressing Bacteria.","authors":"Seong-Young Kwon, Sung-Hwan You, Jin Hee Im, Dinh-Huy Nguyen, Dong-Yeon Kim, Ayoung Pyo, Geun-Joong Kim, Hee-Seung Bom, Yeongjin Hong, Jung-Joon Min","doi":"10.1007/s11307-024-01915-z","DOIUrl":"10.1007/s11307-024-01915-z","url":null,"abstract":"<p><strong>Purpose: </strong>A major obstacle to targeted cancer therapy is identifying suitable targets that are specifically and abundantly expressed by solid tumors. Certain bacterial strains selectively colonize solid tumors and can deliver genetically encoded cargo molecules to the tumor cells. Here, we engineered bacteria to express monomeric streptavidin (mSA) in tumors, and developed a novel tumor pre-targeting system by visualizing the presence of tumor-associated mSA using a biotinylated imaging probe.</p><p><strong>Procedures: </strong>We constructed a plasmid expressing mSA fused to maltose-binding protein and optimized the ribosome binding site sequence to increase solubility and expression levels. E. coli MG1655 was transformed with the recombinant plasmid, expression of which is driven by the pBAD promotor. Expression of mSA was induced by L-arabinose 4 days after injection of bacteria into mice bearing CT26 mouse colon carcinoma cells. Selective accumulation of mSA in tumor tissues was visualized by optical imaging after administration of a biotinylated fluorescent dye. Counting of viable bacterial cells was also performed.</p><p><strong>Results: </strong>Compared with a conventional system, the novel expression system resulted in significantly higher expression of mSA and sustained binding to biotin. Imaging signals in tumor tissues were significantly stronger in the mSA-expressing group than in non-expressing group (P = 0.0005). Furthermore, the fluorescent signal in tumor tissues became detectable again after multiple inductions with L-arabinose. The bacterial counts in tumor tissues showed no significant differences between conditions with and without L-arabinose (P = 0.45). Western blot analysis of tumor tissues confirmed expression and binding of mSA to biotin.</p><p><strong>Conclusions: </strong>We successfully engineered tumor-targeting bacteria carrying a recombinant plasmid expressing mSA, which was targeted to, and expressed in, tumor tissues. These data demonstrate the potential of this novel tumor pre-targeting system when combined with biotinylated imaging probes or therapeutic agents.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"593-602"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[⁶⁸Ga]Ga-labeled FAPI Conjugated with Gly-Pro Sequence for PET Imaging of Malignant Tumors.","authors":"Yuxiang Shang, Guojin Zhang, Xinchao Yao, Chaoquan Lai, Fanghu Wang, Baozhen Zeng, Entao Liu, Hui Yuan, Zhen Cheng, Lei Jiang","doi":"10.1007/s11307-024-01935-9","DOIUrl":"10.1007/s11307-024-01935-9","url":null,"abstract":"<p><strong>Purpose: </strong>To improve tumor uptake and prolong tumor retention, a novel fibroblast activation protein (FAP) ligand based on a quinoline-based FAP inhibitor (FAPI) conjugated with the Gly-Pro sequence and 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA) was radiolabeled with [⁶⁸Ga]GaCl₃ ([⁶⁸Ga]Ga-DOTA-GPFAPI-04). Due to the tumor heterogeneity, this study aimed to further validate the preclinical value of [⁶⁸Ga]Ga-DOTA-GPFAPI-04 PET imaging in tumor mice models with different FAP expression levels.</p><p><strong>Methods: </strong>[⁶⁸Ga]Ga-DOTA-GPFAPI-04 was synthesized and its partition coefficient was measured. The stability of [⁶⁸Ga]Ga-DOTA-GPFAPI-04 was tested in phosphate-buffered saline (PBS, pH 7.4) and fetal bovine serum (FBS). Small animal PET and semi-quantitative studies were conducted in Panc-1 and A549 xenograft tumor mice models compared with [⁶⁸Ga]Ga-DOTA-FAPI-04. Immunofluorescent and immunohistochemical staining and western blot assay were performed to confirm FAP expression in xenograft tumors.</p><p><strong>Results: </strong>[⁶⁸Ga]Ga-DOTA-GPFAPI-04 exhibited a radiochemical purity of > 99% and high stability in PBS and FBS. [⁶⁸Ga]Ga-DOTA-GPFAPI-04 had higher hydrophilic property than [⁶⁸Ga]Ga-DOTA-FAPI-04 (-4.09 ± 0.05 vs -3.45 ± 0.05). Small animal PET and semi-quantitative analysis revealed Panc-1 xenograft tumor displayed higher tumor uptake of [⁶⁸Ga]Ga-DOTA-GPFAPI-04 and tumor-to-background ratios compared to A549 xenograft tumor, consistent with the results of immunofluorescence, immunohistochemistry, and western blot. Moreover, [⁶⁸Ga]Ga-DOTA-GPFAPI-04 demonstrated higher tumor accumulation and longer tumor retention than [⁶⁸Ga]Ga-DOTA-FAPI-04 in both Panc-1 and A549 xenograft tumors. Furthermore, the FAP-binding specificity of [⁶⁸Ga]Ga-DOTA-GPFAPI-04 was confirmed in vivo by co-injection of unlabeled GPFAPI-04.</p><p><strong>Conclusion: </strong>[⁶⁸Ga]Ga-DOTA-GPFAPI-04 showed more favorable in vivo tumor imaging and longer tumor retention compared to [⁶⁸Ga]Ga-DOTA-FAPI-04, which has high potential to be a promising PET probe for detecting FAP-positive tumors.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"729-737"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing SUV Analysis: A Multicenter Study on Preclinical FDG-PET/CT Highlights the Impact of Standardization.","authors":"Claudia Kuntner, Carlos Alcaide, Dimitris Anestis, Jens P Bankstahl, Herve Boutin, David Brasse, Filipe Elvas, Duncan Forster, Maritina G Rouchota, Adriana Tavares, Mari Teuter, Thomas Wanek, Lena Zachhuber, Julia G Mannheim","doi":"10.1007/s11307-024-01927-9","DOIUrl":"10.1007/s11307-024-01927-9","url":null,"abstract":"<p><strong>Purpose: </strong>Preclinical imaging, with translational potential, lacks a standardized method for defining volumes of interest (VOIs), impacting data reproducibility. The aim of this study was to determine the interobserver variability of VOI sizes and standard uptake values (SUV_mean and SUV_max) of different organs using the same [¹⁸F]FDG-PET and PET/CT datasets analyzed by multiple observers. In addition, the effect of a standardized analysis approach was evaluated.</p><p><strong>Procedures: </strong>In total, 12 observers (4 beginners and 8 experts) analyzed identical preclinical [¹⁸F]FDG-PET-only and PET/CT datasets according to their local default image analysis protocols for multiple organs. Furthermore, a standardized protocol was defined, including detailed information on the respective VOI size and position for multiple organs, and all observers reanalyzed the PET/CT datasets following this protocol.</p><p><strong>Results: </strong>Without standardization, significant differences in the SUV_mean and SUV_max were found among the observers. Coregistering CT images with PET images improved the comparability to a limited extent. The introduction of a standardized protocol that details the VOI size and position for multiple organs reduced interobserver variability and enhanced comparability.</p><p><strong>Conclusions: </strong>The protocol offered clear guidelines and was particularly beneficial for beginners, resulting in improved comparability of SUV_mean and SUV_max values for various organs. The study suggested that incorporating an additional VOI template could further enhance the comparability of the findings in preclinical imaging analyses.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"668-679"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437244","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":"Nuclear-Based Labeling of Cellular Immunotherapies: A Simple Protocol for Preclinical Use.","authors":"Alessia Volpe, Serge K Lyashchenko, Vladimir Ponomarev","doi":"10.1007/s11307-024-01923-z","DOIUrl":"10.1007/s11307-024-01923-z","url":null,"abstract":"<p><p>Labeling and tracking existing and emerging cell-based immunotherapies using nuclear imaging is widely used to guide the preclinical phases of development and testing of existing and new emerging off-the-shelf cell-based immunotherapies. In fact, advancing our knowledge about their mechanism of action and limitations could provide preclinical support and justification for moving towards clinical experimentation of newly generated products and expedite their approval by the Food and Drug Administration (FDA).Here we provide the reader with a ready to use protocol describing the labeling methodologies and practical procedures to render different candidate cell therapies in vivo traceable by nuclear-based imaging. The protocol includes sufficient practical details to aid researchers at all career stages and from different fields in familiarizing with the described concepts and incorporating them into their work.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"555-568"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492630","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":"Rapid Assessment of Bio-distribution and Antitumor Activity of the Photosensitizer Bremachlorin in a Murine PDAC Model: Detection of PDT-induced Tumor Necrosis by IRDye® 800CW Carboxylate, Using Whole-Body Fluorescent Imaging.","authors":"Roisin McMorrow, Henriette S de Bruijn, Ivo Que, Debra C Stuurman, Corrina M A de Ridder, Michail Doukas, Dominic J Robinson, Laura Mezzanotte, Clemens W G M Lowik","doi":"10.1007/s11307-024-01921-1","DOIUrl":"10.1007/s11307-024-01921-1","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) is a light-based anticancer therapy that can induce tumor necrosis and/or apoptosis. Two important factors contributing to the efficacy of PDT are the concentration of the photosensitizer in the tumor tissue and its preferential accumulation in the tumor tissue compared to that in normal tissues. In this study, we investigated the use of optical imaging for monitoring whole-body bio-distribution of the fluorescent (660 nm) photosensitizer Bremachlorin in vivo, in a murine pancreatic ductal adenocarcinoma (PDAC) model. Moreover, we non-invasively, examined the induction of tumor necrosis after PDT treatment using near-infrared fluorescent imaging of the necrosis avid cyanine dye IRDye®-800CW Carboxylate. Using whole-body fluorescence imaging, we observed that Bremachlorin preferentially accumulated in pancreatic tumors. Furthermore, in a longitudinal study we showed that 3 hours after Bremachlorin administration, the fluorescent tumor signal reached its maximum. In addition, the tumor-to-background ratio at all-time points was approximately 1.4. Ex vivo, at 6 hours after Bremachlorin administration, the tumor-to-muscle or -normal pancreas ratio exhibited a greater difference than it did at 24 hours, suggesting that, in terms of efficacy, 6 hours after Bremachlorin administration was an effective time point for PDT treatment of PDAC. In vivo administration of the near infrared fluorescence agent IRDye®-800CW Carboxylate showed that PDT, 6 hours after administration of Bremachlorin, selectively induced necrosis in the tumor tissues, which was subsequently confirmed histologically. In conclusion, by using in vivo fluorescence imaging, we could non-invasively and longitudinally monitor, the whole-body distribution of Bremachlorin. Furthermore, we successfully used IRDye®-800CW Carboxylate, a near-infrared fluorescent necrosis avid agent, to image PDT-induced necrotic cell death as a measure of therapeutic efficacy. This study showed how fluorescence can be applied for optimizing, and assessing the efficacy of, PDT.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"616-627"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419835","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":"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":"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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}