MOLECULAR IMAGING AND BIOLOGY

Comparison Between Prone SPECT-Based Semi-Quantitative Parameters and MBI-Based Semi-Quantitative Parameters in Patients with Locally Advanced Breast Cancer
van de Burgt A, van Velden FHP, Corion CLS, Collarino A, Olmos RAV, Smit F, de Geus-Oei LF and Arias-Bouda LMP
This study evaluates the semi-quantitative single-photon emission computed tomography (SPECT) parameters of prone SPECT using [Tc]Tc-sestamibi and compares them with Molecular Breast Imaging (MBI)-derived semi-quantitative parameters for the potential use of response prediction in women with locally advanced breast cancer (LABC).
Quantitative Imaging of Regional Cerebral Protein Synthesis in Clinical Alzheimer's Disease by [C]Leucine PET
Herholz K, McMahon A, Thompson JC, Jones M, Boutin H, Gregory J, Parker CA and Hinz R
Protein synthesis is essential to maintain integrity and function of the human brain, and protein synthesis is associated specifically with the formation of long-term memory. Experimental and clinical observations indicate that this process is disturbed in Alzheimer's dementia and other neurodegenerative diseases. In-vivo investigation with positron emission tomography (PET) using [C]leucine provides a unique possibility to measure regional cerebral protein synthesis (rCPS) rates in human brain and to determine whether it is altered in Alzheimer's disease (AD), and thus may provide a target for future therapeutic interventions.
In Vivo Detection of Lymph Nodes Metastasis of ESCC Using CXCR4-Targeted Tracer [Cu]Cu-NOTA-CP01
Peng T, Li Z, Gao J, Yang M, Qiu Y, Xian J, Bi L, Ye P, Liu Y and Jin H
Esophageal squamous cell carcinoma (ESCC) frequently exhibits skip metastasis to lymph nodes; however, non-invasive imaging techniques capable of directly visualizing metastatic lymph nodes (MLN) are still lacking. Although biopsy is the clinical standard method, it is invasive and poses risks to patient health. This study aims to detect MLN in an intralymphatic tumor metastasis model of ESCC using the CXCR4-targeted tracer [Cu]Cu-NOTA-CP01.
Evaluations of a Cutaneous Wound Healing Model Using Oxygen Enhanced - Dynamic Contrast Enhanced Photoacoustic Imaging (OE-DCE PAI)
Yang E, Khaled A, Liang X, de la Cerda J, Schuler FW, Goel S and Pagel MD
Preclinical models of cutaneous wound healing can be useful for improving clinical wound care. Oxygen Enhanced Photoacoustic imaging (OE PAI) can measure oxygenation, and Dynamic Contrast Enhanced (DCE) PAI can measure vascular perfusion. We investigated how a combined OE-DCE PAI protocol can measure vascular oxygenation and perfusion to a cutaneous healing model.
Optimisation of Animal Handing and Timing of 2-deoxy-2-[F]fluoro-D-glucose PET Tumour Imaging in Mice
Hesketh RL, Lewis DY and Brindle KM
In humans, 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) tumour-to-background contrast continues to increase long after a typical uptake period of 45 - 60 min. Similar studies have not been performed in mice and the static imaging time point for most studies is arbitrarily set at 30 - 60 min post-injection of [F]FDG. Ideally, static PET imaging should be performed after the initial period of rapid uptake but this period has not been defined in mice, with previous dynamic studies in mice being limited to 60 min. This study aimed to define the kinetics of [F]FDG biodistribution over periods of 3 - 4 h in different murine tumour models, both subcutaneous and autochthonous, and to further refine fasting and warming protocols used prior to imaging.
Thymidine Phosphorylase Imaging Probe for Differential Diagnosis of Metabolic dysfunction-associated Steatohepatitis
Higashikawa K, Uehara R, Horiguchi S, Shibata Y, Okubo N, Mizuno Y, Yasui H, Ohnishi S, Takeda H and Kuge Y
Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises simple steatosis (SS), which has a low risk of mortality, and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to liver cirrhosis and hepatocellular carcinoma. Because differentiation between MASH and SS is the most important issue in the diagnosis of MASLD, the establishment of noninvasive diagnostic methods is urgently needed. In this study, we evaluated the potential of [I]IIMU, a thymidine phosphorylase (TYMP) targeted SPECT imaging probe, for differential diagnosis of MASLD in a preclinical animal model.
Using GeoMx DSP Spatial Proteomics to Investigate Immune Infiltration of NOD Mouse Islet and Exocrine Compartments
Tekin H, Lindhardt C, Antvorskov JC, Bager NS, Michaelsen SR, Areškevičiūtė A, Vind JP, Kristensen BW and Josefsen K
Type 1 Diabetes (T1D) pathogenesis involves immune cells infiltrating pancreatic Islets of Langerhans, leading to T cell activation, beta cell destruction, and impaired insulin production. However, infiltration has a heterogenic nature that isn't described in detail, as not all islets are infiltrated. The aim of this study was to investigate if the observed heterogeneity is coupled to differences in immune and/or dysfunctional status of islets or exocrine cells, and if specific markers could elucidate mechanistic details of T1D pathogenesis.
Effects of Neoadjuvant Therapy on Tumour Target Expression of Oesophageal Cancer Tissue for NIR Fluorescence Imaging
Galema HA, Neijenhuis LKA, Lauwerends LJ, Dekker-Ensink NG, Verhoef C, Vahrmeijer AL, Bhairosingh SS, Kuppen PJK, Rogalla S, Burggraaf J, Lagarde SM, Wijnhoven BPL, Hutteman M, Doukas M, Keereweer S and Hilling DE
Oesophaegal cancer patients with a clinical complete response (CR) after neoadjuvant chemoradiotherapy (nCRT) are candidates for an active surveillance strategy. Regrowth rates of 40% after initial clinical CR indicate that identification of a true complete response to nCRT remains challenging. Near-infrared tumour-specific fluorescence endoscopic imaging might help to discriminate patients with a true complete response from patients with residual disease. This study aims to find potential markers to enable molecular imaging in oesophageal cancer and to assess the effect of nCRT on marker expression.
The Potential Utility of (2S,4R)-4-[F]fluoroglutamine as a Novel Metabolic Imaging Marker for Inflammation Explored by Rat Models of Arthritis and Paw Edema
Kim MJ, Akula HK, Marden J, Li K, Hu B, Vaska P and Qu W
(2S,4R)-4-[F]fluoroglutamine ([F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent on glutamine metabolism like cancer cells, we explored the potential utility of [F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA).
Utility of Quantitative Assessment of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl Human Serum Albumin SPECT/CT in the Identification of Severe Liver Fibrosis: Its Complementary Diagnostic Value with Other Liver Function Indices
Kozaki Y, Ichikawa Y, Nakamura S, Kobayashi T, Tomita Y, Nagata M, Kuriyama N, Mizuno S and Sakuma H
To evaluate the value of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (Tc-GSA) single photon emission computed tomography (SPECT) for assessing liver fibrosis, and to assess its complementary value to other liver function indices such as fibrosis-4 (FIB-4) index and indocyanine green (ICG) clearance test parameters (ICG-R15 and ICG-K).
Differentiation Between Responders and Non-Responders to Antibiotic Treatment in Mice Using F-Fluorodeoxysorbitol/PET
Li J, Zheng H, Olson J, Warawa JM and Ng CK
Bacterial infection causes significant mortality and morbidity worldwide despite the availability of antibiotics. Differentiation between responders and non-responders early on during antibiotic treatment will be informative to patients and healthcare providers. Our objective was to investigate whether PET imaging with F-Fluorodeoxysorbitol (F-FDS) or F-FDG can be used to differentiate responders from non-responders to antibiotic treatment.
Prospective Comparison of [F]FDG and [F]AIF-FAPI-74 PET/CT in the Evaluation of Potentially Resectable Pancreatic Ductal Adenocarcinoma
Yun WG, Gil J, Choi H, Han Y, Jung HS, Cho YJ, Suh M, Kwon W, Lee YS, Cheon GJ and Jang JY
Accurate clinical staging of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is critical for establishing optimal treatment strategies. While the efficacy of fluorine-18-fluorodeoxyglucose ([F]FDG) positron emission tomography/computed tomography (PET/CT) in clinical staging is unclear, PET/CT detecting fibroblast-activation protein (FAP) expression has recently received considerable attention for detecting various tumors, including PDAC, with high sensitivity. We explored the efficacy of [F]FDG and [F]AIF-FAPI-74 PET/CT in the initial evaluation of potentially resectable PDAC.
Correction: Cryo-Fluorescence Tomography as a Tool for Visualizing Whole-Body Inflammation Using Perfluorocarbon Nanoemulsion Tracers
Leach BI, Lister D, Adams SR, Bykowski J, Schwartz AB, McConville P, Dimant H and Ahrens ET
2023 World Molecular Imaging Congress Program
Ultrasound Imaging of Macrophages Intracellularly Labelled with Biosynthetic Gas Vesicles
Xue R, Liu Z, Liu L, Sun S and Gong Z
This study aimed to develop a novel method for real-time imaging to track macrophages and to make it possible to visually track their dynamic features.
Radioimaging Foam Cells Infiltrating Atherosclerotic Plaques in Mice Using I-labeled oxLDL as a Radiotracer
Izawa M, Kawashima H, Okuno Y, Nakaya J, Takeda M, Harada K, Yamada Y, Nishimura K, Ishihara K, Akiba S and Takata K
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 (I-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 I-oxLDL and DiI-labeled oxLDL (DiI-oxLDL). Accumulation of I-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/I-oxLDL via CD36, but not LDL/I-LDL. The radioactive signal from I-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 I-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 I-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.
Usefulness of the Primary Tumor Standardized Uptake Value of Iodine-123 Metaiodobenzylguanidine for Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma
Hirahara M, Nakajo M, Kitazano I, Jinguji M, Tani A, Takumi K, Kamimura K, Tanimoto A and Yoshiura T
To examine the usefulness of semi-quantitative analysis using the standardized uptake value (SUV) of iodine-123 metaiodobenzylguanidine ([I]-MIBG) for predicting metastatic potential in patients with pheochromocytoma (PHEO) and paraganglioma (PGL).
Chemokine Receptor 4-Targeted PET/CT with [Ga]pentixather in Newly Diagnosed Multiple Myeloma: a Comparative Study with [Ga]pentixafor PET/CT
Yang Q, Zhang F, Hao Z, Zhuang J and Huo L
This study aimed to compare the detection rate of [Ga]pentixather PET/CT and [Ga]pentixafor PET/CT in newly diagnosed multiple myeloma (NDMM) patients, and to explore the value of [Ga]pentixather PET/CT for tumor load assessment.
Improved Quantification of MicroPET/CT Imaging Using CT-derived Scaling Factors
Nandi A, Nakano M, Brašić JR, Brinson ZS, Kitzmiller K, Mathur A, Mohamed M, Roberts J, Wong DF and Kuwabara H
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) in rodent PET studies.
Immunohistochemical Evaluation of Cathepsin B, L, and S Expression in Breast Cancer Patients
Linders DGJ, Bijlstra OD, Fallert LC, Dekker-Ensink NG, March TL, Pool M, Walker E, Straight B, Basilion JP, Bogyo M, Burggraaf J, Hilling DE, Vahrmeijer AL, Kuppen PJK and Crobach ASLP
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.
Neurotoxin-Derived Optical Probes for Elucidating Molecular and Developmental Biology of Neurons and Synaptic Connections. Toxin-Derived Optical Probes for Neuroimaging
Bijjam R, Shorter S, Bratt AM, O'Leary VB, Ntziachristos V and Ovsepian SV
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.