Molecular Imaging and Biology最新文献

{"title":"Investigation of the Impact of the H310A FcRn Region Mutation on ⁸⁹Zr-Immuno-PET Brain Imaging with a BBB-Shuttle Anti‑Amyloid Beta Antibody.","authors":"Thomas E Wuensche, Natascha Stergiou, Iris Mes, Mariska Verlaan, Esther J M Kooijman, Albert D Windhorst, Allan Jensen, Ayodeji A Asuni, Benny Bang-Andersen, Guus A M S van Dongen, Danielle J Vugts, Wissam Beaino","doi":"10.1007/s11307-024-01931-z","DOIUrl":"10.1007/s11307-024-01931-z","url":null,"abstract":"<p><strong>Purpose: </strong>In the emerging field of antibody treatments for neurodegenerative diseases, reliable tools are needed to evaluate new therapeutics, diagnose and select patients, monitor disease progression, and assess therapy response. Immuno-PET combines the high affinity and exceptional specificity of monoclonal antibodies with the non-invasive imaging technique positron emission tomography (PET). Its application in neurodegenerative disease brain imaging has been limited due to the marginal uptake across the blood-brain barrier (BBB). The emergence of BBB-shuttle antibodies with enhanced uptake across the BBB extended immuno-PET to brain imaging. We recently reported about specific brain uptake of a bispecific aducanumab mTfR antibody in APP/PS1 TG mice using ⁸⁹Zr-immuno-PET. However, a sufficient target-to-background ratio was reached at a relatively late scanning time point of 7 days post-injection. To investigate if a better target-to-background ratio could be achieved earlier, an aducanumab BBB-shuttle with a mutated Fc region for reduced FcRn affinity was evaluated.</p><p><strong>Procedures: </strong>Adu^H310A-8D3 and Adu-8D3 were modified with DFO*-NCS and subsequently radiolabeled with ⁸⁹Zr. The potential influence of the H310A mutation, modification with DFO*-NCS, and subsequent radiolabeling on the in vitro binding to amyloid-beta and mTfR1 was investigated via amyloid-beta peptide ELISA and FACS analysis using mTfR1 transfected CHO-S cells. Blood kinetics, brain uptake, in vivo PET imaging and target engagement of radiolabeled Adu^H310A-8D3 were evaluated and compared to non-mutated Adu-8D3 in APP/PS1 TG mice and wild-type animals as controls.</p><p><strong>Results: </strong>Radiolabeling was performed with sufficient radiochemical yields and radiochemical purity. In vitro binding to amyloid-beta and mTfR1 showed no impairment. [⁸⁹Zr]Zr-Adu^H310A-8D3 showed faster blood clearance and earlier differentiation of amyloid-beta-related brain uptake compared to [⁸⁹Zr]Zr-Adu-8D3. However, only half of the brain uptake was observed for [⁸⁹Zr]Zr-Adu^H310A-8D3.</p><p><strong>Conclusions: </strong>Although a faster blood clearance of Adu^H310A-8D3 was observed, it was concluded that no beneficial effects for ⁸⁹Zr-immuno-PET imaging of brain uptake were obtained.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"823-834"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875355","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":"Neurotoxin-Derived Optical Probes for Elucidating Molecular and Developmental Biology of Neurons and Synaptic Connections. \u0000Toxin-Derived Optical Probes for Neuroimaging.","authors":"Rohini Bijjam, Susan Shorter, Alison M Bratt, Valerie B O'Leary, Vasilis Ntziachristos, Saak Victor Ovsepian","doi":"10.1007/s11307-024-01954-6","DOIUrl":"10.1007/s11307-024-01954-6","url":null,"abstract":"<p><p>Botulinum neurotoxins (BoNTs) and tetanus toxin (TeTX) are the deadliest biological substances that cause botulism and tetanus, respectively. Their astonishing potency and capacity to enter neurons and interfere with neurotransmitter release at presynaptic terminals have attracted much interest in experimental neurobiology and clinical research. Fused with reporter proteins or labelled with fluorophores, BoNTs and TeTX and their non-toxic fragments also offer remarkable opportunities to visualize cellular processes and functions in neurons and synaptic connections. This study presents the state-of-the-art optical probes derived from BoNTs and TeTX and discusses their applications in molecular and synaptic biology and neurodevelopmental research. It reviews the principles of the design and production of probes, revisits their applications with advantages and limitations and considers prospects for future improvements. The versatile characteristics of discussed probes and reporters make them an integral part of the expanding toolkit for molecular neuroimaging, promoting the discovery process in neurobiology and translational neurosciences.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350311","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":"Immunohistochemical Evaluation of Cathepsin B, L, and S Expression in Breast Cancer Patients.","authors":"Daan G J Linders, Okker D Bijlstra, Laura C Fallert, N Geeske Dekker-Ensink, Taryn L March, Martin Pool, Ethan Walker, Brian Straight, James P Basilion, Matthew Bogyo, Jacobus Burggraaf, Denise E Hilling, Alexander L Vahrmeijer, Peter J K Kuppen, A Stijn L P Crobach","doi":"10.1007/s11307-024-01955-5","DOIUrl":"10.1007/s11307-024-01955-5","url":null,"abstract":"<p><strong>Purpose: </strong>Cysteine cathepsins are proteases that play a role in normal cellular physiology and neoplastic transformation. Elevated expression and enzymatic activity of cathepsins in breast cancer (BCa) indicates their potential as a target for tumor imaging. In particular cathepsin B (CTSB), L (CTSL), and S (CTSS) are used as targets for near-infrared (NIR) fluorescence imaging (FI), a technique that allows real-time intraoperative tumor visualization and resection margin assessment. Therefore, this immunohistochemical study explores CTSB, CTSL, and CTSS expression levels in a large breast cancer patient cohort, to investigate in which BCa patients the use of cathepsin-targeted NIR FI may have added value.</p><p><strong>Procedures: </strong>Protein expression was analyzed in tumor tissue microarrays (TMA) of BCa patients using immunohistochemistry and quantified as a total immunostaining score (TIS), ranging from 0-12. In total, the tissues of 557 BCa patients were included in the TMA.</p><p><strong>Results: </strong>CTSB, CTSL, and CTSS were successfully scored in respectively 340, 373 and 252 tumors. All tumors showed CTSB, CTSL, and/or CTSS expression to some extent (TIS > 0). CTSB, CTSL, and CTSS expression was scored as high (TIS > 6) in respectively 28%, 80%, and 18% of tumors. In 89% of the tumors scored for all three cathepsins, the expression level of one or more of these proteases was scored as high (TIS > 6). Tumors showed significantly higher cathepsin expression levels with advancing Bloom-Richardson grade (p < 0.05). Cathepsin expression was highest in estrogen receptor (ER)-negative, human epidermal growth factor receptor 2(HER2)-positive and triple-negative (TN) tumors. There was no significant difference in cathepsin expression between tumors that were treated with neoadjuvant systemic therapy and tumors that were not.</p><p><strong>Conclusions: </strong>The expression of at least one of the cysteine cathepsins B, L and S in all breast tumor tissues tested suggests that cathepsin-activatable imaging agents with broad reactivity for these three proteases will likely be effective in the vast majority of breast cancer patients, regardless of molecular subtype and treatment status. Patients with high grade ER-negative, HER2-positive, or TN tumors might show higher imaging signals.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350310","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":"Improved Quantification of MicroPET/CT Imaging Using CT-derived Scaling Factors.","authors":"Ayon Nandi, Masayoshi Nakano, James Robert Brašić, Zabecca S Brinson, Kelly Kitzmiller, Anil Mathur, Mona Mohamed, Joshua Roberts, Dean F Wong, Hiroto Kuwabara","doi":"10.1007/s11307-024-01947-5","DOIUrl":"10.1007/s11307-024-01947-5","url":null,"abstract":"<p><strong>Purpose: </strong>Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dimensions and consequently estimates of nondisplaceable binding potential (BP_ND) in rodent PET studies.</p><p><strong>Procedures: </strong>PET and CT scans were acquired on 5 female and 5 male CD-1 mice with 3-[¹⁸F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([¹⁸F]FPEB), a radiotracer for the metabotropic glutamate receptor subtype 5 (mGluR5). In the proposed PET/CT (PTCT) approach, the tracer-specific standard volume was dimension-customized to each animal using the scaling factors from CT-to-standard CT coregistration to simplify PET-to-standard PET coregistration (i.e., 3 CT- and 6 PET-derived parameters). For comparison, conventional PET-based coregistration was performed with 9 (PT9) or 12 (PT12) parameters. PET frames were transferred to the standard space by the three approaches (PTCT, PT9, and PT12) to obtain regional time-activity curves (TACs) and BP_ND in 14 standard volumes of interest (VOIs). Lastly, CT images of the animals were transferred to the standard space by CT-based parameters from PTCT and with the scaling factors replaced with those from PET-based PT9 to evaluate agreement of the skull to the standard CT.</p><p><strong>Results: </strong>The PET-based approaches showed various degrees of underestimations of scaling factors in the posterior-anterior-direction compared to PTCT, which resulted in negatively proportional overestimation of radioactivity in the cerebellum (reference region) up to 20%, and proportional, more prominent underestimation of BP_ND in target regions down to -50%. The skulls of individual animals agreed with the standard skull for scaling factors from PTCT but not for the scaling factors from PT9, which suggested inaccuracy of the latter.</p><p><strong>Conclusions: </strong>The results indicated that conventional PET-based coregistration approaches could yield biased estimates of BP_ND in proportion to errors of brain dimensions when applied to tracers for which the cerebellum serves as reference region. The proposed PTCT provides evidence of a quantitative improvement over PET-based approaches for brain studies using micro-PET/CT scanners.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308078","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":"Chemokine Receptor 4-Targeted PET/CT with [⁶⁸Ga]pentixather in Newly Diagnosed Multiple Myeloma: a Comparative Study with [⁶⁸Ga]pentixafor PET/CT.","authors":"Qiao Yang, Fujing Zhang, Zhixin Hao, Junling Zhuang, Li Huo","doi":"10.1007/s11307-024-01953-7","DOIUrl":"https://doi.org/10.1007/s11307-024-01953-7","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to compare the detection rate of [⁶⁸Ga]pentixather PET/CT and [⁶⁸Ga]pentixafor PET/CT in newly diagnosed multiple myeloma (NDMM) patients, and to explore the value of [⁶⁸Ga]pentixather PET/CT for tumor load assessment.</p><p><strong>Methods: </strong>Nineteen NDMM Patients were prospectively recruited and underwent both [⁶⁸Ga]pentixather PET/CT and [⁶⁸Ga]pentixafor PET/CT. A positive PET scan was defined as the presence of PET-positive focal bone lesions, paraskeletal disease, extramedullary plasmacytoma, or diffuse bone marrow uptake. Lesion numbers, SUVmax and PET-related tumor burden values were compared. The correlations between PET-related tumor burden and clinical risk stratification were analyzed.</p><p><strong>Results: </strong>[⁶⁸Ga]pentixather PET/CT showed a tendency of higher positive rate compared with [⁶⁸Ga]pentixafor PET/CT [94.7% (18/19) vs. 78.9% (15/19), p > 0.05]. Among 14 patients with 151 matched focal bone lesions, [⁶⁸Ga]pentixather PET detected more or equal number of lesions in 13 patients, and demonstrated higher uptake value than ⁶⁸ Ga-pentixafor PET [SUVmax, 16.8 (9.0, 23.8) vs. 13.4 (6.5, 20.4), p < 0.001]. For PET related-tumor burden, positive correlations of total bone marrow uptake (TBmU) (r = 0.9540, p < 0.0001) and SUVmean of total bone marrow (r = 0.9632, p < 0.0001) in two PET scans were observed. Higher TBmU [7864.9 (5549.2, 11,616.2) vs. 5383.4(4102.7, 11,041.8), p < 0.001], SUVmean of total bone marrow [1.4 (1.1, 2.2) vs. 1.1 (0.7, 2.1), p < 0.001] were demonstrated on [⁶⁸Ga]pentixather PET than [⁶⁸Ga]pentixafor PET. And the level of TBmU in [⁶⁸Ga]pentixather PET and [⁶⁸Ga]pentixafor PET were both elevated in Durie-Salmon Staging (DSS) III than DSS I (p < 0.01).</p><p><strong>Conclusions: </strong>[⁶⁸Ga]pentixather PET/CT performed a non-inferior capability for tumor detection compared to [⁶⁸Ga]pentixafor PET/CT in NDMM patients. [⁶⁸Ga]pentixather PET/CT can assess tumor load in MM patients and depict a significantly higher PET-related total tumor burden than [⁶⁸Ga]pentixafor PET/CT.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291484","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":"Usefulness of the Primary Tumor Standardized Uptake Value of Iodine-123 Metaiodobenzylguanidine for Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma","authors":"Mitsuho Hirahara, Masatoyo Nakajo, Ikumi Kitazano, Megumi Jinguji, Atsushi Tani, Koji Takumi, Kiyohisa Kamimura, Akihide Tanimoto, Takashi Yoshiura","doi":"10.1007/s11307-024-01952-8","DOIUrl":"https://doi.org/10.1007/s11307-024-01952-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>To examine the usefulness of semi-quantitative analysis using the standardized uptake value (SUV) of iodine-123 metaiodobenzylguanidine ([¹²³I]-MIBG) for predicting metastatic potential in patients with pheochromocytoma (PHEO) and paraganglioma (PGL).</p><h3 data-test=\"abstract-sub-heading\">Procedures</h3><p>This study included 18 PHEO and 2 PGL patients. [¹²³I]-MIBG visibility and SUV-related parameters (SUVmax, SUVmean, tumor volume of [¹²³I]-MIBG uptake [TV_MIBG], and total lesion [¹²³I]-MIBG uptake) were compared with the pathological grading obtained using the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP), which are used to predict metastatic potential. The PASS scores were categorized as &lt; 4 and ≥ 4. Based on the GAPP scores, PHEOs/PGLs were categorized as follows: well, moderately, and poorly differentiated tumors. The Mann–Whitney U test or Spearman’s rank correlation was used to assess differences or associations between two quantitative variables.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>All PHEOs/PGLs were visualized on [¹²³I]-MIBG scintigraphy. There were 16 PASS &lt; 4 and 4 PASS ≥ 4 tumors. Moreover, 11 and 9 tumors were well and moderately differentiated, respectively. The uptake scores and SUV-related parameters significantly differed between tumors with a PASS score of &lt; 4 and those with a PASS score of ≥ 4 (each, <i>p</i> &gt; 0.05). Moderately differentiated tumors had significantly higher uptake scores and SUV-related parameters except TV_MIBG than well-differentiated tumors (each, <i>p</i> &lt; 0.05). The GAPP score was positively correlated with the uptake scores and SUV-related parameters (each, <i>p</i> &lt; 0.05) except TV_MIBG.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The primary tumor [¹²³I]-MIBG uptake assessed using SUV-related parameters can be an imaging tool for predicting metastatic potential in patients with PHEO/PGL.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":"44 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253781","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":"Radioimaging Foam Cells Infiltrating Atherosclerotic Plaques in Mice Using 125I-labeled oxLDL as a Radiotracer","authors":"Michi Izawa, Hidekazu Kawashima, Yui Okuno, Junna Nakaya, Mayuko Takeda, Koki Harada, Yuri Yamada, Kaneyasu Nishimura, Keiichi Ishihara, Satoshi Akiba, Kazuyuki Takata","doi":"10.1007/s11307-024-01951-9","DOIUrl":"https://doi.org/10.1007/s11307-024-01951-9","url":null,"abstract":"<p>Bioimaging such as magnetic resonance is used to monitor atherosclerotic plaques consisting of foam cells, which are derived from macrophages that have ingested oxidized low-density lipoprotein (oxLDL). However, the current bioimaging techniques are not highly specific and sensitive in detecting foam cells, calling for the development of higher precision foam cell detection probes. Here, we investigated the utility of iodine-125-labeled oxLDL (¹²⁵I-oxLDL) as a prototype radiotracer in the radioimaging of foam cells infiltrating atherosclerotic plaques. Mouse bone marrow-derived macrophages (BMDMs) were used to analyze oxLDL uptake. Atherosclerosis mouse model was injected with ¹²⁵I-oxLDL and DiI-labeled oxLDL (DiI-oxLDL). Accumulation of ¹²⁵I-oxLDL and DiI-oxLDL in foam cells infiltrating atherosclerotic plaques was examined using Oil Red O (ORO) staining, autoradiography, and fluorescent immunohistochemistry. BMDMs phagocytosed oxLDL/¹²⁵I-oxLDL via CD36, but not LDL/¹²⁵I-LDL. The radioactive signal from ¹²⁵I-oxLDL phagocytosed by the BMDMs could be detected for at least 3 days. In atherosclerosis mouse model, atherosclerotic plaques formed in the aortic arches and valves. The radioactive signal of the injected ¹²⁵I-oxLDL was detected in atherosclerotic plaques of the aortic arch, and its intensity was positively correlated with the lesion size. Furthermore, the DiI-oxLDL fluorescent signals were detected in foam cells accumulating in atherosclerotic plaques. Thus, we found that ¹²⁵I-oxLDL can be used as a radiotracer in the radioimaging of foam cells in atherosclerotic plaques by autoradiography, suggesting its potential future applications in bioimaging methods such as single-photon emission computed tomography.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":"45 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253782","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":"Challenges in Pharmacokinetic Modelling of [¹⁸F]fluoro-PEG-folate PET/CT Imaging in Epithelial Ovarian Cancer Patients.","authors":"Thomas Ruytenberg, Isabeau A Ciggaar, Inge T A Peters, Wyanne A Noortman, Petra Dibbets-Schneider, Lysanne D A N de Muynck, Joeri Kuil, Cornelis D de Kroon, Tom J M Molenaar, Hendrik J F Helmerhorst, Lenka M Pereira Arias-Bouda, Alexander L Vahrmeijer, Albert D Windhorst, Floris H P van Velden, Katja N Gaarenstroom, Lioe-Fee de Geus-Oei","doi":"10.1007/s11307-024-01922-0","DOIUrl":"10.1007/s11307-024-01922-0","url":null,"abstract":"<p><strong>Purpose: </strong>To describe the pharmacokinetic properties of the [¹⁸F]fluoro-polyethylene glycol(PEG)-folate radiotracer in PET/CT imaging of patients with advanced stage epithelial ovarian cancer (EOC).</p><p><strong>Procedures: </strong>In five patients with advanced EOC (FIGO stage IIIB/IIIC, Fédération Internationale de Gynécologie et d'Obstétrique), a 90-min dynamic PET acquisition of the pelvis was performed directly after i.v. administration of 185 MBq [¹⁸F]fluoro-PEG₆-folate. Arterial blood samples collected at nineteen timepoints were used to determine the plasma input function. A static volume of interest (VOI) for included tumor lesions was drawn manually on the PET images. Modelling was performed using PMOD software. Three different models (a 1-tissue compartment model (1T2k) and two 2-tissue compartment models, irreversible (2T3k) and reversible (2T4k)) were compared in goodness of fit with the time activity curves by means of the Akaike information criterion.</p><p><strong>Results: </strong>The pharmacokinetic analysis in the pelvic area has proven to be much more challenging than expected. Only four out of 22 tumor lesions in five patients were considered suitable to perform modelling on. The remaining tumor lesions were inapt due to either low tracer uptake, small size, proximity to other [¹⁸F]fluoro-PEG₆-folate -avid structures and/or displacement by abdominal organ motion in the dynamic scan. Data from the four analyzed tumor lesions suggest that the irreversible 2T3k may best describe the pharmacokinetics. All 22 lesions were immunohistochemically stained positive for the folate receptor alpha (FRα) after resection.</p><p><strong>Conclusion: </strong>Performing pharmacokinetic analysis in the abdominal pelvic region is very challenging. This brief article describes the challenges and pitfalls in pharmacokinetic analysis of a tracer with high physiological accumulation in the intestines, in case of lesions of limited size in the abdominal pelvic area.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"577-584"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076255","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":"A Phase 2 Multicenter Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer with a pH-Activatable Nanoprobe.","authors":"Gregory T Kennedy, Feredun S Azari, Austin Chang, Patrick Bou-Samra, Charuhas Desphande, Jarrod Predina, Edward J Delikatny, Madeline Olson, David C Rice, Sunil Singhal","doi":"10.1007/s11307-024-01933-x","DOIUrl":"10.1007/s11307-024-01933-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Intraoperative molecular imaging (IMI) uses tumor-targeted optical contrast agents to improve identification and clearance of cancer. Recently, a probe has been developed that only fluoresces when activated in an acidic pH, which is common to many malignancies. We report the first multicenter Phase 2 trial of a pH-activatable nanoprobe (pegsitacianine, ONM-100) for IMI of lung cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Patients with suspected or biopsy-confirmed lung cancer scheduled for sublobar resection were administered a single intravenous infusion of pegsitacianine (1 mg/kg) one to three days prior to surgery. Intraoperatively, the patients underwent a white light thoracoscopic evaluation, and then were imaged with an NIR thoracoscope to detect tumor fluorescence. The primary study endpoint was the proportion of patients with a clinically significant event (CSE) which was defined as an intraoperative discovery during IMI that led to a change in the surgical procedure. Possible CSEs included (i) localizing the index lung nodule that could not be located by white light, (ii) identifying a synchronous malignant lesion, or (iii) recognizing a close surgical margin (&lt; = 10 mm). Secondary endpoints were sensitivity, specificity, NPV, and PPV of pegsitacianine in detecting tumor-containing tissue. The safety evaluation was based on adverse event reporting, clinical laboratory parameters, and physical examinations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty patients were confirmed as eligible and administered pegsitacianine. Most of the patients were female (n = 12 [60%]), middle-aged (mean age 63.4 years), and former smokers (n = 13 [65%], 28.6 mean pack years). Mean lesion size was 1.9 cm, and most lesions (n = 17 [85%]) were malignant. The most common histologic subtype was adenocarcinoma (n = 9). By utilizing IMI with pegsitacianine, one patient had a CSE in the detection of a close margin and another had localization of a tumor not detectable by traditional surgical means. Six of 19 (31.6%) malignant lesions fluoresced with mean tumor-to-background ratio (TBR) of 3.00, as compared to TBR of 1.20 for benign lesions (n = 3). Sensitivity and specificity of pegsitacianine-based IMI for detecting malignant tissue was 31.6% and 33.3%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of pegsitacianine-based IMI was 75% and 7.1%, respectively. Pegsitacianine-based imaging was not effective in differentiating benign and malignant lymph nodes. From a safety perspective, no drug-related serious adverse events occurred. Four patients experienced mild pegsitacianine-related infusion reactions which required discontinuing the study drug with complete resolution of symptoms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Pegsitacianine-based IMI, though well tolerated from a safety perspective, does not consistently label lung tumors during resection and does not provide significant clinical benefit over existing s","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"585-592"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590774","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":"In vivo Hyperpolarized Metabolic Imaging to Monitor the Progression of Hepatitis B Virus (HBV)-Related Hepatitis to Liver Fibrosis.","authors":"Chung Man Moon, Suk Hee Heo, Yong Yeon Jeong, Yun Young Lee, Seul Kee Kim, Sang Soo Shin","doi":"10.1007/s11307-024-01936-8","DOIUrl":"10.1007/s11307-024-01936-8","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess metabolic changes to monitor the progression from normal liver to hepatitis B virus (HBV)-related hepatitis and liver fibrosis using hyperpolarized ¹³C magnetic resonance imaging (MRI).</p><p><strong>Procedures: </strong>Hepatitis was induced in mice (n = 16) via hydrodynamic injection of HBV 1.2 plasmid (25 μg). Among them, liver fibrosis was induced in the mice (n = 8) through weight-adapted administration of thioacetamide with ethanol. Normal control mice (n = 8) were injected with a phosphate buffer solution. Subsequently, a hyperpolarized ¹³C MRI was performed on the mouse liver in vivo. The level of hepatitis B surface antigen (HBsAg) in blood serum was measured. Statistical analysis involved comparing the differential metabolite ratios, blood biochemistry values, and body weight among the three groups using the Kruskal-Wallis one-way analysis of variance.</p><p><strong>Results: </strong>HBsAg was absent in the normal and fibrosis groups, while it was detected in the hepatitis group. The ratios of [1-¹³C] lactate/pyruvate, [1-¹³C] alanine/pyruvate, [1-¹³C] lactate/total carbon, and [1-¹³C] alanine/total carbon were significantly lower in the normal control group than in the hepatitis and fibrosis groups (p < 0.05). Moreover, these ratios were significantly higher in the fibrosis group than in the hepatitis group (p < 0.05). However, no significant differences were observed in either [1-¹³C] pyruvate-hydrate/pyruvate or [1-¹³C] pyruvate-hydrate/total carbon among the three groups.</p><p><strong>Conclusions: </strong>The levels of [1-¹³C] lactate and [1-¹³C] alanine in vivo may serve as valuable indicators for differentiating between HBV-related hepatitis, liver fibrosis, and normal liver.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"649-657"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590776","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}