Tumor Molecular Imaging Research Articles

Enzymatically Cyclic Activated Biosensor Based on a Tetrahedral DNA Framework for Precise Tumor in Situ Molecular Imaging.

The development of stimulus-responsive and amplification-based strategies is crucial for achieving improved spatial specificity and enhanced sensitivity in tumor molecular imaging, addressing challenges such as off-tumor signal leakage and limited biomarker content. Therefore, a cyclically activated enzymatic biosensor based on the modification of an AP site within a tetrahedral framework DNA (AP-tFNA) was rationally developed for tumor cell-specific molecular imaging using the endogenous enzyme apurinic/apyrimidinic endonuclease 1 (APE1) as a target, exhibiting superior spatial specificity and high sensitivity. APE1, which predominantly localizes within the nucleus in normal cells but exhibits cytosolic and nucleus expression in cancer cells, can specifically recognize and cleave the AP site in AP-tFNA, resulting in the separation of the fluorophore and quenching group, thereby inducing a fluorescence signal. Additionally, upon completion of the excision of one AP site in AP-tFNA, APE1 is released, thereby initiating a subsequent cycle of hydrolytic cleavage reactions. The experimental results demonstrated that AP-tFNA enables precise differentiation of tumor cells both in vitro and in vivo. In particular, the AP-tFNA can monitor drug resistance in neuroblastoma cells and classify the risk for neuroblastoma patients at the clinical plasma level.

The Current Status and Future Directions on Nanoparticles for Tumor Molecular Imaging.

Molecular imaging is an advanced technology that utilizes specific probes or markers in conjunction with cutting-edge imaging techniques to observe and analyze the localization, distribution, activity, and interactions of biomolecules within living organisms. Tumor molecular imaging, by enabling the visualization and quantification of molecular characteristics of tumor cells, facilitates a deeper and more comprehensive understanding of tumors, providing valuable insights for early diagnosis, treatment monitoring, and cancer biology research. However, the image quality of molecular imaging still requires improvement, and nanotechnology has significantly propelled the advancement of molecular imaging. Currently, nanoparticle-based tumor molecular imaging technologies encompass radionuclide imaging, fluorescence imaging, magnetic resonance imaging, ultrasound imaging, photoacoustic imaging, and multimodal imaging, among others. As our understanding of the tumor microenvironment deepens, the design of nanoparticle probes for tumor molecular imaging has also evolved, offering new perspectives and expanding the applications of tumor molecular imaging. Beyond diagnostics, there is a marked trend towards integrated diagnosis and therapy, with image-guided treatment playing a pivotal role. This includes image-guided surgery, photodynamic therapy, and chemodynamic therapy. Despite continuous advancements and innovative developments in molecular imaging, many of these remain in the experimental stage and require breakthroughs before they can be fully integrated into clinical practice.

New insights into red blood cells in tumor precision diagnosis and treatment.

Red blood cells (RBCs), which function as material transporters in organisms, are rich in materials that are exchanged with metabolically active tumor cells. Recent studies have demonstrated that tumor cells can regulate biological changes in RBCs, including influencing differentiation, maturation, and morphology. RBCs play an important role in tumor development and immune regulation. Notably, the novel scientific finding that RBCs absorb fragments of tumor-carrying DNA overturns the conventional wisdom that RBCs do not contain nucleic acids. RBC membranes are excellent biomimetic materials with significant advantages in terms of their biocompatibility, non-immunogenicity, non-specific adsorption resistance, and biodegradability. Therefore, RBCs provide a new research perspective for the development of tumor liquid biopsies, molecular imaging, drug delivery, and other tumor precision diagnosis and treatment technologies.

Design and experimental validation of a new radiolabeled analog of N-(3-hydroxy-4-methoxy-phenyl-methyl) ferrocene-carboxamide (VFC) targeting the TRPV1 receptor

The TRPV1 receptor has been recognized to play a role in cancer development, being overexpressed in prostate, breast, lung, and colon cancers. Since TRPV1 activation promotes cancer cell proliferation, invasion, and migration, TRPV1 antagonists may show potential as anti-cancer agents. Capsaicin and capsaicinoids are phytochemicals derived from homovanillic acid found in abundance in chili peppers and responsible for its pungent properties. Capsaicin acts as a potent agonist of TRPV1 with recognized antineoplastic properties. Here, we employ computational approaches including molecular modeling and docking to refine the 3D structure of human TRPV1 and assess its interaction with the newly synthesized N-(3-hydroxy-4-methoxyphenylmethyl)ferrocenecarboxamide (VFC) and its cyclopentadienyl tricarbonyl rhenium and technetium analogs. Radiolabeling of VFC with 99mTc was achieved by double ligand exchange to afford 99mTc-VFC in high radiochemical purity and yield. Biodistribution studies in mice demonstrated preferential accumulation of 99mTc-VFC in the bladder, liver, kidney, and lung. These findings may contribute to developing efficient TRPV1-targeted radiotracers for molecular imaging of tumors by SPECT.

An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging.

Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.

The Relationship Between the Molecular Phenotypes of Brain Gliomas and the Imaging Features and Sensitivity of Radiotherapy and Chemotherapy

Gliomas are the most common primary malignant tumors of the brain, accounting for about 80% of all central nervous system malignancies. With the development of molecular biology, the molecular phenotypes of gliomas have been shown to be closely related to the process of diagnosis and treatment. The molecular phenotype of glioma also plays an important role in guiding treatment plans and evaluating treatment effects and prognosis. However, due to the heterogeneity of the tumors and the trauma associated with the surgical removal of tumor tissue, the application of molecular phenotyping in glioma is limited. With the development of imaging technology, functional magnetic resonance imaging (MRI) can provide structural and function information about tumors in a noninvasive and radiation-free manner. MRI is very important for the diagnosis of intracranial lesions. In recent years, with the development of the technology for tumor molecular diagnosis and imaging, the use of molecular phenotype information and imaging procedures to evaluate the treatment outcome of tumors has become a hot topic. By reviewing the related literature on glioma treatment and molecular typing that has been published in the past 20 years, and referring to the latest 2020 NCCN treatment guidelines, summarizing the imaging characteristic and sensitivity of radiotherapy and chemotherapy of different molecular phenotypes of glioma. In this article, we briefly review the imaging characteristics of different molecular phenotypes in gliomas and their relationship with radiosensitivity and chemosensitivity of gliomas.

Progress in research of tumor biomarkers and molecular imaging probes for gastric cancer

Progress in research of tumor biomarkers and molecular imaging probes for gastric cancer

Integrin α6: a potential target for cancer molecular imaging and targeting therapy

AbstractAs a major kind of cell surface adhesion molecules with signal transduction function, integrins play a major role in tumorigenesis and tumor progression. The role of integrins in tumor cells and the tumor microenvironment has been extensively revealed. Among the integrin family, integrin αvβ3 is the most studied integrin in the past 20 years. Plenty of preclinical and clinical studies have been conducted, which showed clinical benefits of targeting integrin αvβ3 in tumor imaging and treatment. Currently, the focus of interest is gradually shifting from integrin αvβ3 toward other integrin subtypes. Integrin α6 is expressed in many malignant tumors, such as colorectal cancer, head and neck squamous cell carcinoma, breast cancer, pancreatic cancer, and liver cancer, and its expression is correlated with poor survival of the patients. Recent studies have shown that tumor molecular imaging agents and therapeutic drugs targeting integrin α6 have excellent safety and efficacy in preclinical mouse models, encouraging clinical translation of this promising target. In this review, we briefly overview the physiological and pathological function of integrin α6 and highlight the recent advances in integrin α6‐targeted imaging and therapeutics in tumors.

Application of aptamer-functionalized nanomaterials in molecular imaging of tumors

Abstract Cancer is one of the most important causes of human death. Early diagnosis and treatment can make patients live longer. Therefore, there is an urgent need to develop early and accurate diagnosis method for tumors. Molecular imaging technology can be used for qualitative and quantitative analyses at cellular and molecular levels, which provides a new technology for accurate diagnosis of tumors. In recent years, various nanomaterials with unique properties have been used for tumor molecular imaging. Meanwhile, aptamers are becoming an indispensable element in the design of functional nanomaterials because of their small size, high stability, and convenient modification, especially giving nanomaterials the ability to recognize specific targets. Therefore, aptamer-functionalized nanomaterials (AFNs) provide unprecedented opportunities for the field of tumor diagnosis. Here we focus on the latest development of AFNs in the molecular imaging of tumors. First, we introduce the characteristics and advantages of common aptamer-modified organic nanomaterials and inorganic nanomaterials. Then, the applications of AFNs in fluorescence imaging, computed tomography, magnetic resonance imaging, radionuclide imaging, ultrasound imaging, photoacoustic imaging, and multimode fusion imaging are discussed. Finally, we provide some perspectives on the challenges and opportunities that have arisen from this promising area.

DOTATOC PET/CT imaging of a typical carcinoid tumor in a human ex-vivo perfused lung lobe.

The use of Isolated lung perfusion (ILP), combined with medical imaging modalities such as positron emission tomography-computed tomography (PET/CT), provides real-time visualization of tumors in ventilated and perfused vital lung tissue. This experiment intends to show the feasibility and benefits of using ILP combined with PET/CT imaging. Following lung surgery on a 49-year-old male, his left lower lobectomy specimen, which held a typical carcinoid tumor, was preserved on normothermic ILP. Gallium-68-Edotreotide ([68Ga]-DOTATOC) was administered into the ILP circuit, and dynamic emission data from PET/CT was acquired. ILP was carried out for 120 minutes. Near physiologic gas exchange and glucose metabolism were preserved throughout the experiment. The time activity curves (TAC) of 5 different volumes of interest (VOI) showed notable differences in tracer uptake over time. The peripheral area of the carcinoid exhibited delayed but high somatostatin receptor agonist uptake compared to the surrounding parenchyma and the intrapulmonary artery. However, the central area of the carcinoid showed very low [68Ga]-DOTATOC uptake. This experiment demonstrates the potential of ILP combined with PET/CT for kinetic modeling in experimental nuclear medicine imaging. By providing visualization of tracer uptake in perfused lung tissue, this model could potentially improve our understanding of tumor physiology and molecular imaging.

Near-infrared targeted EGFR fluorescent probe for tumor imaging and diagnosis

The incidence of prostate cancer has increased rapidly in recent years. And the detection of tumor markers is an effective way for early diagnosis and poor prognosis. Prostate cancer is associated with growth factor receptors. Epidermal growth factor receptor (EGFR) expression is increased in a majority of prostate cancer patients. Peptide probes have the advantages of convenient modification and selective and rapid clearance in the molecular imaging of tumors. H1 is a short peptide designed and modified based on the CDR3 region of a nanobody targeting the epidermal growth factor receptor (EGFR) with high affinity for malignant tumors that overexpress EGFR. The CDR3 sequence of nanobodies has a long finger-like structure that allows deep interaction with the cryptic epitope of the antigen. Here we synthesized a sensitive fluorescent peptide probe of H1 conjugated to imaging moieties MPA. Experimental data showed that H1-MPA targets EGFR with high affinity. Meanwhile, H1-MPA has high tumor uptake and a strong signal-to-noise ratio. In addition, the near-infrared fluorescent probe H1-MPA can determine tumor boundaries and can be used to monitor and prevent tumor metastasis, including hepatic metastasis, for accurate tumor diagnosis. H1-MPA provides a promising tool for cancer diagnosis.

Clinical characteristics associated with the development of preoperative and postoperative seizures in patients with glioblastoma (P3-1.002)

<h3>Objective:</h3> To determine the factors which predict the occurrence of preoperative seizures (PRS) and post-operative seizures (POS) among patients with glioblastoma (GBM). <h3>Background:</h3> Seizures have been well described in patients with GBM, albeit at a lower frequency than low grade gliomas. Although recent studies suggest epileptogenesis has more to do with genetic molecular markers in low grade glioma-related seizure, information on factors that influence the development of of GBM-related PRS and POS is lacking. <h3>Design/Methods:</h3> We performed a single-center retrospective cohort study of patients with GBM evaluated at Mayo Clinic Florida, between 2018 and 2022. Clinical factors including, tumor molecular markers, neurophysiological and imaging findings were analyzed according to the status of PRS and POS. <h3>Results:</h3> One hundred thirty-two adult patients (median age=61.5 years), 79 (59.85%) females) were included. The most common locations were the temporal (n=50, 42.02%) and frontal (n=47, 39.50%) lobes. All patients underwent GBM resection, with 17.1% undergoing total resection (n=22). Sixty-two patients (46.27%) underwent intra-operative electrocorticography during GBM resection. Isocitrate dehydrogenase 1 (IDH1) wildtype was present in 121 patients (90.3%), 61 patients had O⁶-methylguanine-DNA methyltransferase (<i>MGMT</i>)-methylated GBM (46.21%). Forty patients (33.9%) had PRS, and 39 patients (38.24%) had POS (median follow-up=17.27 months; IQR=10.6–30.1). IDH1 wildtype and MGMT methylation status were not associated with PRS or POS. Patients with PRS were younger (59 years vs. 64 years, <b><i>p=0.021</i></b>) and experienced a longer survival time (16.1 months vs. 8.3 months, <b><i>p=0.044</i></b>) compared to patients without PRS. Occipital lobe GBM was associated with a lower likelihood of PRS (<b><i>p=0.043</i></b>) and POS (<b><i>p=0.001</i></b>). <h3>Conclusions:</h3> PRS is associated with younger age and longer survival time. PRS and POS are less likely to occur with occipital lobe tumors. Further studies are needed to confirm our findings and elucidate the influence of other tumor molecular markers in the development of PRS and POS in patients with GBM. <b>Disclosure:</b> Dr. Sánchez Boluarte has nothing to disclose. Dr. Garcia has nothing to disclose. Dr. Gunasekera has nothing to disclose. Dr. Tatum has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bioserenity. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Defense Law Firm on behalf of a patient with epilepsy with funds donated to the Epilepsy Foundation of America. The institution of Dr. Tatum has received research support from Esai. The institution of Dr. Tatum has received research support from Mayo Clinic. The institution of Dr. Tatum has received research support from Liva Nova. The institution of Dr. Tatum has received research support from Engage Pharmaceuticals. The institution of Dr. Tatum has received research support from Xenon. Dr. Tatum has received publishing royalties from a publication relating to health care. Dr. Tatum has received publishing royalties from a publication relating to health care. Dr. Sirven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Sirven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medtronic. Dr. Sirven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurelis. Dr. Sirven has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Sirven has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. Dr. Sirven has stock in Doximity. Dr. Sirven has received publishing royalties from a publication relating to health care. Dr. Sirven has a non-compensated relationship as a Host with WJCT Public Media/ NPR that is relevant to AAN interests or activities. Dr. Freund has nothing to disclose. The institution of Dr. Ritaccio has received research support from NIH. Dr. Ritaccio has received intellectual property interests from a discovery or technology relating to health care. Kaisorn Chaichana has nothing to disclose. Alfredo Quiñones-Hinojosa has nothing to disclose. Dr. Feyissa has nothing to disclose.

Progress of photoacoustic imaging combined with targeted photoacoustic contrast agents in tumor molecular imaging.

Molecular imaging visualizes, characterizes, and measures biological processes at the molecular and cellular level. In oncology, molecular imaging is an important technology to guide integrated and precise diagnosis and treatment. Photoacoustic imaging is mainly divided into three categories: photoacoustic microscopy, photoacoustic tomography and photoacoustic endoscopy. Different from traditional imaging technology, which uses the physical properties of tissues to detect and identify diseases, photoacoustic imaging uses the photoacoustic effect to obtain the internal information of tissues. During imaging, lasers excite either endogenous or exogenous photoacoustic contrast agents, which then send out ultrasonic waves. Currently, photoacoustic imaging in conjunction with targeted photoacoustic contrast agents is frequently employed in the research of tumor molecular imaging. In this study, we will examine the latest advancements in photoacoustic imaging technology and targeted photoacoustic contrast agents, as well as the developments in tumor molecular imaging research.

Dual-Modality Molecular Imaging of Tumor via Quantum Dots-Liposome-Microbubble Complexes.

Molecular imaging has demonstrated promise for evaluating the expression levels of biomarkers for the early prediction of tumor progression and metastasis. However, most of the commonly used molecular imaging modalities are relatively single and have difficulties imaging complex biological processes. Here, we fabricated αvβ3-integrin-targeted quantum-dots-loaded liposome-microbubble (iRGD-QDLM) complexes that combined ultrasound imaging with optical imaging. The resulting iRGD-QDLM has excellent binding capability to 4T1 breast cancer cells. Ultrasound molecular imaging of 4T1 tumors demonstrated that significantly enhanced ultrasound molecular signals could be observed in comparison with non-targeted QDLM. Importantly, our study also suggested that iRGD-QDL on the surface of microbubbles could be delivered into a tumor by ultrasound-mediated microbubble destruction and adhered to αvβ3 integrin on breast cancer cells, achieving transvascular fluorescent imaging. Our study provides a novel approach to dual-modality molecular imaging of αvβ3 integrin in the tumor tissue.

Into the future: a pilot study combining imaging with molecular profiling for preoperative prediction of resectability in ovarian cancer (068)

Objectives: We sought to determine the joint predictive value of tumor molecular subtype and CT imaging data in predicting surgical outcomes prior to primary debulking surgery (PDS) in Stage IIIC/IV high-grade serous ovarian cancer patients. Methods: Patients undergoing PDS for Stage IIIC/IV were included. Based on CT imaging, a continuous CT-score indicative of overall disease burden was defined based on six CT measurements of anatomic involvement: (1) diaphragm disease; (2) gastrohepatic/porta hepatis; (3) root of superior mesenteric artery; (4) presence of moderate to severe ascites; (5) intrahepatic lesion, and (6) diffuse peritoneal thickening > 4mm. Patients were then classified as CT-low or CT-high if their score was ≤2 or ≥3, respectively. Molecular subtypes were derived from mRNA profiling of chemo-naïve tumors; women were classified as having mesenchymal (MES) subtype or non-MES subtype tumors. Patients were classified as having no gross residual disease (RD0) or any gross residual disease less than 1 cm (RD1), or gross residual disease greater than 1 cm (RD2). Multivariate regression models were fit to predict RD. The four cohorts, (i) non-MES & CT-low, (ii) non-MES & CT-high, (iii) MES & CT-low, and (iv) MES & CT-high, were compared with Fisher’s exact tests to examine the association with RD and surgical complexity. Graphical Abstract View Large Image Figure Viewer Download Hi-res image Conclusions: Preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced OC to better triage these cases to alternative approaches. Objectives: We sought to determine the joint predictive value of tumor molecular subtype and CT imaging data in predicting surgical outcomes prior to primary debulking surgery (PDS) in Stage IIIC/IV high-grade serous ovarian cancer patients. Methods: Patients undergoing PDS for Stage IIIC/IV were included. Based on CT imaging, a continuous CT-score indicative of overall disease burden was defined based on six CT measurements of anatomic involvement: (1) diaphragm disease; (2) gastrohepatic/porta hepatis; (3) root of superior mesenteric artery; (4) presence of moderate to severe ascites; (5) intrahepatic lesion, and (6) diffuse peritoneal thickening > 4mm. Patients were then classified as CT-low or CT-high if their score was ≤2 or ≥3, respectively. Molecular subtypes were derived from mRNA profiling of chemo-naïve tumors; women were classified as having mesenchymal (MES) subtype or non-MES subtype tumors. Patients were classified as having no gross residual disease (RD0) or any gross residual disease less than 1 cm (RD1), or gross residual disease greater than 1 cm (RD2). Multivariate regression models were fit to predict RD. The four cohorts, (i) non-MES & CT-low, (ii) non-MES & CT-high, (iii) MES & CT-low, and (iv) MES & CT-high, were compared with Fisher’s exact tests to examine the association with RD and surgical complexity. Conclusions: Preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced OC to better triage these cases to alternative approaches.

LGG-16. Retrospective and integrative analyses of molecular characteristics and their specific imaging parameters in pediatric grade 1 gliomas.

Pediatric low-grade gliomas (PLGG) are the most common brain tumors diagnosed during childhood and represent a heterogeneous group associating variable molecular abnormalities. To go further and develop specific statistical patterns integrating altogether tumor molecular background, imaging features and patient outcome, a retrospective study was performed in a group of non-NF1 grade 1 PLGGs. So, 78 children, followed from 2004 to 2017, were retrospectively reported. Their therapeutic management comprised surgery or surgery plus chemotherapies (e.g., carboplatin and vincristine). In this population, radiological and molecular patterns were pooled statistically to be able to identify specific prognostic subgroups. Considering all 78 patients, 59 had only a surgical removal and 19 patients were treated with post-operative chemotherapy. Twelve progressions were reported in the partially resected and chemotherapeutic groups, whereas 4 deaths occurred only in the highly treated patients. As expected, PLGG with BRAF pV600E and/or CDKN2A loss exhibited poor outcomes. Nevertheless, we were able to evidence statistically significant associations between molecular characteristics and their specific imaging presentation on diagnostic and 24-week MRIs. In the chemo-treated patients, the molecularly good risk situations were significantly linked to the presence of a large tumor cyst at diagnosis (> 50% of the tumor volume (TV)) and the appearance during treatment of a higher cystic proportion that we called “cystic conversion”. So, additionally to the WHO prognostic molecular patterns, precise MRI characteristics (notably cystic part proportions onto TV) were associated to BRAF p.V600E PLGGs, as well as to the more frequent molecular KIAA1549-BRAF fused PLGGs. To summarize, absence on diagnostic MRI of cystic parts and/or cystic conversion at 6-month chemotherapy time point were significantly linked to a worst prognosis and response to treatment. In future studies, these imaging features might be considered as innovative prognostic markers to use during treatment.

Retrospective and integrative analyses of molecular characteristics and their specific imaging parameters in pediatric grade 1 gliomas.

Pediatric low-grade gliomas (PLGG) are the most common brain tumors diagnosed during childhood and represent a heterogeneous group associating variable molecular abnormalities. To go further and develop specific statistical patterns between tumor molecular background, imaging features, and patient outcome, a retrospective study was performed in a group of non-neurofibromatosis type 1 (non-NF1) grade 1 PLGGs. Seventy-eight children, followed from 2004 to 2017, were retrospectively reported. In this population, we analyzed radiological and molecular parameters. Their therapeutic management comprised surgery or surgery plus chemotherapies. Considering all 78 patients, 59 had only a surgical removal and 19 patients were treated with postoperative chemotherapy. Twelve progressions were reported in the partially resected and chemotherapeutic groups, whereas four deaths occurred only in the highly treated patients. As expected, in the global cohort, PLGG with BRAF p.V600E and/or CDKN2A loss exhibited poor outcomes and we evidenced significant associations between those molecular characteristics and their imaging presentation. In the chemo-treated patients, when associating initial and 6-month magnetic resonance imaging (MRI) parameters to the molecular features, the good risk situations were significantly linked to the presence of a large tumor cyst at diagnosis and the appearance during treatment of a higher cystic proportion that we called cystic conversion. So, additionally to the presence of BRAF p.V600E or CDKN2A deletion in grade 1 PLGGs, the absence on diagnostic MRI of cystic parts and/or cystic conversion at 6-month chemotherapy were significantly linked to a worst prognosis and response to treatment. These imaging features should be considered as prognostic markers in future PLGG studies.

Secretin Receptor as a Target in Gastrointestinal Cancer: Expression Analysis and Ligand Development.

Secretin was originally discovered as a gastrointestinal peptide that stimulates fluid secretion from the pancreas and liver and delays gastric emptying. In disease, a secretin receptor (SCTR) was found to occur as a splice variant in gastrinoma and pancreatic adenocarcinoma. Overexpression of SCTR has been described for gastrinomas, carcinoid tumors of the lung and cholangiocarcinoma. SCTR therefore is considered a candidate target for molecular tumor imaging as well as for peptide receptor radioligand therapy (PRRT) in a number of oncological indications. The aim of this study was to characterize SCTR expression in esophageal and pancreatic cancer, demonstrating for the first time high SCTR overexpression in these tumor types. In total, 65 of 70 pancreatic ductal adenocarcinoma tissues stained strongly positive for SCTR in immunohistochemistry, as did most of the 151 esophageal cancer samples, with minor influence of grading in both entities. In addition, the aim of this study was to further delineate residues in human secretin that are critical for binding to and activation of human SCTR. For a potential development of short and metabolically stable analogs for clinical use, it was intended to probe the peptide for its capacity to incorporate deletions and substitutions without losing its affinity to SCTR. In a systematic approach, a library of 146 secretin variants containing single amino acid substitutions as well as truncations on either end was tested in β-arrestin2-GFP translocation and fluorescent ligand internalization assays employing high-content analysis, in cAMP assays which run in agonist and antagonist mode, and in radioligand binding. The main structural determinants of SCTR binding and activation were localized to the N-terminus, with His1, Asp3 being among the most sensitive positions, followed by Phe6, Thr7 and Leu10. Aminoterminal truncation caused a rapid decline in receptor activity and most of these variants proved to be partial agonists showing antagonistic properties. In this study, the most potent novel antagonist showed an IC50 of 309 ± 74 nM in the β-arrestin2-GFP translocation assay on human SCTR while remaining a weak partial agonist. Future studies will have to demonstrate the utility of further enhanced secretin analogues as tracers for in vivo imaging and therapy.

Copper‐Catalyzed Covalent Dimerization of Near‐Infrared Fluorescent Cyanine Dyes: Synergistic Enhancement of Photoacoustic Signals for Molecular Imaging of Tumors

AbstractInvited for this month's cover is the group of Prof. Samuel Achilefu at the Washington University School of Medicine and colleagues at the Pohang University of Science and Technology. The cover picture shows copper (the hammer) catalyzing the assembly of monomeric near‐infrared fluorescent dye molecules, cypate (yellow glow), into covalently‐linked dimeric molecules (merged red balls). More information can be found in the Communication at 10.1002/anse.202100045.

Front Cover: Copper‐Catalyzed Covalent Dimerization of Near‐Infrared Fluorescent Cyanine Dyes: Synergistic Enhancement of Photoacoustic Signals for Molecular Imaging of Tumors (Anal. Sens. 1/2022)

The cover picture shows copper (hammer)-catalyzes the assembly of monomeric near-infrared fluorescent dye molecules, cypate (yellow glow), into covalently-linked dimeric molecules (merged red balls). Dimerization induces fluorescence quenching due to enhanced photothermal dissipation (red hot flashes), which generates acoustic waves. Decorating the dimers with a tumor-targeting agent, LS301, facilitates selective tumor uptake of the probes, which are detectable in vivo by photoacoustic imaging. More information can be found in the Communication by Samuel Achilefu, Chulhong Kim and co-workers.