American journal of nuclear medicine and molecular imaging最新文献

HER2 overexpression is associated with various tumor types and prompted the development of targeted therapies. Previously, iso-[²¹¹At]SGMAB-5F7 was developed as a HER2-targeted alpha therapy agent, demonstrating promising therapeutic efficacy in the preclinical stage. Aiming for an ¹⁸F-labeled tracer for companion diagnostics in clinical translation, we employed the Al¹⁸F-RESCA strategy in our current work and investigated whether [¹⁸F]AlF-RESCA-5F7 could visualize HER2 expression in vivo. [¹⁸F]AlF-RESCA-5F7 was attained with high radiochemical purity (> 99%) and molar activity in the range of 16.5 ± 8.8 GBq/μmol (n = 8). Compared to previously reported radiotracers that contained 5F7 as the HER2-targeting carrier and fluorine-18 as the positron-emitting isotope, the radiosynthesis was simplified to one single step within 30 min. The dissociation constant of [¹⁸F]AlF-RESCA-5F7 was determined as 3.3 nM via saturation binding assay using SKOV3 ovarian carcinoma cells. Tumor uptake of the novel tracer in Balb/c nude mice bearing SKOV3 xenografts was 4.69 ± 1.51, 3.34 ± 0.82 and 3.77 ± 0.99 %ID/g at 1, 2, and 4 h post-injection. Even though high retention of radioactivity was seen in the kidneys, micro-PET/CT imaging of [¹⁸F]AlF-RESCA-5F7 delineated the tumor up to 4 h post-injection with minimal activity in the gallbladder, intestines, and bone. This study suggests that [¹⁸F]AlF-RESCA-5F7 is a promising HER2 PET radiotracer with an eased radiolabeling method. Whether [¹⁸F]AlF-RESCA-5F7 could work as a companion diagnostic agent to assist in patient stratification and treatment monitoring of iso-[²¹¹At]SGMAB-5F7 warrants further investigation.

[This corrects the article on p. 106 in vol. 10, PMID: 32419979.].

Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [¹⁸F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [¹⁸F]FDG PET/CT in diagnosing various causes of FUO. [¹⁸F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [¹⁸F]FDG PET/CT can be used in the work-up of FUO.

Infection with the Human Immunodeficiency Virus (HIV) is one of the most pressing issues facing public health on a worldwide scale. Currently, HIV-related lymphoma is the most common cause of death among people living with HIV, and warrants more attention. The unique challenges associated with HIV-related lymphoma management derive from the underlying HIV infection and its immunosuppressive effects. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has gained significant prominence in the past few years as a valuable diagnostic and therapeutic instrument for the treatment of HIV-related lymphoma. This review will start with an overview of the subtypes, risk factors, and therapeutic choices for individuals with HIV-related lymphoma. We will then briefly discuss the current application of ¹⁸F-FDG PET/CT in the medical management of HIV-related lymphoma patients, followed by the initial staging of the disease, the evaluation of therapeutic response, the prediction of prognostic outcomes, the decision-making process for radiotherapy guided by PET findings, and the distinguishing of various diagnoses.

This study aimed to assess the efficacy of fluor-18 fluorodeoxyglucose (¹⁸F-FDG) PET/CT using sub-regional-based radiomics in predicting epidermal growth factor receptor (EGFR) mutation status in pretreatment patients with solid lung adenocarcinoma. A retrospective analysis included 269 patients (134 EGFR+ and 135 EGFR-) who underwent pretreatment ¹⁸F-FDG PET/CT scans and EGFR mutation testing. The most metabolically active intratumoral sub-region was identified, and radiomics features from whole tumors or sub-regional regions were used to build classification models. The dataset was split into a 7:3 ratio for training and independent testing. Feature subsets were determined by Pearson correlation and the Kruskal Wallis test and radiomics classifiers were built with support vector machines or logistic regressions. Evaluation metrics, including accuracy, area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were employed for different classifiers. Results indicated that the sub-region-based classifier outperformed the whole-tumor classifier in terms of accuracy (73.8% vs. 66.2%), AUC (0.768 vs. 0.632), specificity (65.0% vs. 50.0%), PPV (70.2% vs. 62.2%), and NPV (78.8% vs. 74.0%). The clinical classifier exhibited an accuracy of 75.0%, AUC of 0.768, sensitivity of 72.5%, specificity of 77.5%, PPV of 76.3%, and NPV of 73.8%. The combined classifier, incorporating sub-region analysis and clinical parameters, demonstrated further improvement with an accuracy of 77.5%, AUC of 0.807, sensitivity of 77.5%, specificity of 77.5%, and NPV of 77.5%. The study suggests that sub-region-based ¹⁸F-FDG PET/CT radiomics enhances EGFR mutation prediction in solid lung adenocarcinoma, providing a practical and cost-efficient alternative to invasive EGFR testing.

Molecular imaging enables visualization and characterization of biological processes that influence tumor behavior and response to therapy. The TMTP1 (NVVRQ) peptide has shown remarkable affinity to highly metastatic tumors and and its potential receptor is aminopeptidase P2. In this study, we have designed and synthesized a ⁶⁸Ga-labeled cyclic TMTP1 radiotracer (⁶⁸Ga-DOTA-TMTP1), for PET imaging of cervical cancer. The goal of this study was to investigate the properties of this radiotracer and its tumor diagnostic potential. The radiochemical yield of ⁶⁸Ga-DOTA-TMTP1 was high and the radiochemical purity was greater than 95%. The octanol-water partition coefficient for ⁶⁸Ga-DOTA-TMTP1 was -2.76 ± 0.08 and ⁶⁸Ga-DOTA-TMTP1 has showed excellent stability in in vitro studies. The cellular uptake and efflux of ⁶⁸Ga-DOTA-TMTP1 in paired highly metastatic and lowly metastatic cervical cancer cell line HeLa and C-33A as well as normal cervical epithelial cell line End1 were measured in a γ counter. ⁶⁸Ga-DOTA-TMTP1 exhibited higher uptake in HeLa cells than in C-33A cells. The binding to HeLa and C-33A cells could be blocked by excess TMTP1. On microPET images, HeLa tumors were clearly visualized within 60 min and the uptake of the radiotracer in HeLa tumors was higher than that of C-33A tumors. After blocking with TMTP1, HeLa tumors uptake was significantly reduced and the specificity ⁶⁸Ga-DOTA-TMTP1 was thus validated. Overall, we have successfully synthesized ⁶⁸Ga-DOTA-TMTP1 with high yield and high specific activity and have demonstrated its potential role for highly metastatic tumor-targeted diagnosis.

Sarcoidosis is a systemic inflammatory disease that affects multiple organs. Various clinical signs are associated with cardiac sarcoidosis (CS), and the diagnosis process is complicated because any organ could be involved. Despite the critical clinical importance of early and precise diagnosis of CS, there is currently no gold-standard method for CS evaluation. The non-invasive imaging modalities of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and cardiac magnetic resonance (CMR) imaging have demonstrated the potential for identifying various histological characteristics of CS. Recently, the development of hybrid FDG-PET/CMR scanners has enabled the simultaneous acquisition of these attributes. Compared to just one imaging modality, these scanners detect CS and stratify risk more accurately and with higher sensitivity. Analyzing the potential role of concurrent FDG-PET/CMR in enhancing the diagnosis of CS, the present review concentrates on the advantages of this technique in light of recent technological developments.

The macrophage colony-stimulating factor 1 receptor (CSF1R) is almost exclusively expressed in microglia, representing a biomarker target for imaging of microglia availability. [¹¹C]CPPC has specific binding affinity to CSF1R and suitable kinetic properties for in vivo PET imaging of microglia. However, previous studies reported a low radiochemical yield, motivating additional research to optimize [¹¹C]CPPC radiochemistry. In this work, we report an automated radiosynthesis of [¹¹C]CPPC on a Synthra MeIPlus module with improved radiochemical yield. The final [¹¹C]CPPC product was obtained with excellent chemical/radiochemical purities and molecular activity, facilitating high-quality in-human PET imaging applications.

The strategic installation of a [¹⁸F]fluorine atom at the specific position of the lead molecule is a never-ending challenge for radiochemists in their endeavour to develop novel positron emission tomography (PET) imaging applications. Although the radiosynthesis of [¹⁸F]CF₂H-containing molecules has been explored in the past decade, more methods need to be explored for various well-functionalized compounds. Recently, two novel strategies of radiodifluoromethylation were reported, namely the utilization of [¹⁸F]difluorocarbene building block and frustrated Lewis pair-mediated C-¹⁸F bond formation, respectively. These methods provide an efficient radiofunctionalization of complex CF₂H-containing molecules for drug discovery and PET ligand development.

As a regulator in renin-angiotensin-aldosterone system, angiotensin-converting enzyme 2 (ACE2) closely correlated with tumor progression of pancreatic cancer, meantime, was easily affected by a variety of factors. [^99mTc]Tc-cyc-DX600 SPECT was established as an ACE2-specific imaging protocol to figure out the ACE2 status in pancreatic tumor. BALB/C-NU mice were used to prepare the subcutaneous cell derived xenograft (CDX) models with HEK-293T or HEK-293T/hACE2 cells to validate ACE2 specificity of [^99mTc]Tc-cyc-DX600 SPECT and establish SPECT imaging protocol. On the basis of [^99mTc]Tc-cyc-DX600 SPECT and [¹⁸F]F-FDG PET/CT, ACE2-dependence on tumor size and tumor metabolism were further verified on orthotopic pancreatic cancer model with KPC cells. Immunohistochemical analysis was used to demonstrate the findings on ACE2 SPECT. [^99mTc]Tc-cyc-DX600 was of superior tumor uptake in HEK-293T/hACE2 CDX than wild type (6.74 ± 0.31 %ID/mL vs 1.83 ± 0.26 %ID/mL at 1.5 h post injection (p.i.); 3.14 ± 0.31 %ID/mL vs 1.16 ± 0.15 %ID/mL at 4.5 h p.i.). For the CDX models with PANC-1 cells, a significant negative correlation between the slope of tumor volume and tumor uptake was observed (r = -0.382 for the 1-4th day; r = -0.146 for the 1-5th day; r = -0.114 for the 1-6th day; r = -0.152 for the 1-7th day; but P > 0.05 for all). For orthotopic pancreatic cancer model, the linear correlation between FDG PET and ACE2 SPECT of the pancreatic lesions was negative (r = -0.878), the quantitative values of ACE2 SPCET was positively correlated with the volume of primary lesions (r = 0.752) and also positively correlated with the quantitative values of ACE2 immunohistochemical analysis (r = 0.991). Conclusively, [^99mTc]Tc-cyc-DX600 SPECT is an ACE2-specific imaging protocol with clinical translational potential, adding multidimensional information on the disease progression of pancreatic cancer.