American journal of nuclear medicine and molecular imaging最新文献

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.

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.

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 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.

Adenoid cystic carcinoma (ACC) is a rare salivary gland cancer. Still, its growth and invasion progress is slow, and its hematogenous metastasis is ACC's most common distant metastasis. Because of the broad expression and low background uptake of fibroblast activation protein (FAP) in tumor stroma, FAPI is considered another potential tracer of ACC in addition to FDG. In this case, we report a patient who was diagnosed with metastatic ACC liver cancer by fine needle aspiration biopsy (FNAB) and underwent PET/CT examination of [¹⁸F]FDG and [¹⁸F]FAPI-42 to find the primary cancer lesion. Finally, the primary cancer lesion was found in the left submandibular gland and was pathologically confirmed as ACC after resection.

Several therapeutics and biomarkers that target Alzheimer's disease (AD) are under development. Our clinical positron emission tomography (PET) research programs are interested in six radiopharmaceuticals to image patients with AD and related dementias, specifically [¹¹C]UCB-J and [¹⁸F]SynVesT-1 for synaptic vesicle glycoprotein 2A as a marker of synaptic density, two vesicular acetylcholine transporter PET radiotracers: [¹⁸F]FEOBV and [¹⁸F]VAT, as well as the transmembrane AMPA receptor regulatory protein (TARP)-γ8 tracer, [¹⁸F]JNJ-64511070, and the muscarinic acetylcholine receptor (mAChR) M4 tracer [¹¹C]MK-6884. The goal of this study was to compare all six radiotracers (labeled with tritium or ¹⁸F) by measuring their density variability in pathologically diagnosed cases of AD, mild cognitive impairment (MCI) and normal healthy volunteer (NHV) human brains, using thin-section in vitro autoradiography (ARG). Region of interest analysis was used to quantify radioligand binding density and determine whether the radioligands provide a signal-to-noise ratio optimal for showing changes in binding. Our preliminary study confirmed that all six radiotracers show specific binding in MCI and AD. An expected decrease in their respective target density in human AD hippocampus tissues compared to NHV was observed with [³H]UCB-J, [³H]SynVesT-1, [³H]JNJ-64511070, and [³H]MK-6884. This preliminary study will be used to guide human PET imaging of SV2A, TARP-γ8 and the mAChR M4 subtype for imaging in AD and related dementias.

High-grade serous ovarian cancer (HGSOC) is the most common type of epithelial ovarian cancer with insidious onset, rapid growth, and invasive spread. Here, we reported the diagnosis and treatment of a 53-year-old patient with a history of hysterectomy aided by the ⁶⁸Ga-FAPI PET/MR scan. The patient was first presented to the local hospital with a lump on the left side of the neck with a biopsy suggesting metastatic cancer. Pelvic ultrasonography revealed two irregular masses. After admission, tumor markers, pathology consultation of the biopsy, and the ⁶⁸Ga-FAPI PET/MR scan were administered. The biopsy of the lump suggested poorly differentiated adenocarcinoma and CA125 was elevated at 530.6 U/ml. The ⁶⁸Ga-FAPI PET/MR scan showed several abnormal lymph nodes and two soft tissue masses with borders of dispersed restriction displaying internally uneven signals depicted by slightly elongated T1 and T2 signals within the pelvic cavity suggesting that pelvic mass could be the primary lesion. The patient received cytoreductive surgery including bilateral adnexectomy, omentectomy, and appendectomy. Post-surgical pathology suggested left and right HGSOC with left fallopian tube invasion. The patient completed six courses of first-line chemotherapy and remained progression-free for 14 months up to date. To conclude, ⁶⁸Ga-FAPI PET/MR aids in primary tumor determination and tumor burden assessment and provides a guide for the management of late-stage HGSOC patients.

In the current issue of American Journal of Nuclear Medicine and Molecular Imaging, Vasdev et al. presented a work entitled "In Vitro Evaluation of PET Radiotracers for Imaging Synaptic Density, the Acetylcholine Transporter, AMPA-tarp-γ8 and Muscarinic M4 receptors in Alzheimer's disease". In which, in vitro autoradiography studies using radioligands were employed as a valuable tool to gain more insights for potential clinical translation. In this invited perspective, we would like to briefly introduce the current state of AD diagnosis, especially PET imaging on synapse, and highlight the advances of PET imaging in pre-clinic and clinic that might assist on precise therapy in the future.