American journal of nuclear medicine and molecular imaging最新文献

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.

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.

Poly(ADP-ribose) polymerase (PARP) activation often indicates a disruptive signal to lipid metabolism, the physiological alteration of which may be implicated in the development of non-alcoholic fatty liver disease. The objective of this study was to evaluate the capability of [⁶⁸Ga]DOTA-PARPi PET to detect hepatic PARP expression in a non-alcoholic steatohepatitis (NASH) mouse model. In this study, male C57BL/6 mice were subjected to a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for a 12-week period to establish preclinical NASH models. [⁶⁸Ga]DOTA-PARPi PET imaging of the liver was conducted at the 12-week mark after CDAHFD feeding. Comprehensive histopathological analysis, covering hepatic steatosis, inflammation, fibrosis, along with blood biochemistry, was performed in both NASH models and control groups. Despite the induction of severe inflammation, steatosis and fibrosis in the liver of mice with the CDAHFD-NASH model, PET imaging of NASH with [⁶⁸Ga]-DOTA-PARPi did not reveal a significantly higher uptake in NASH models compared to the control. This underscores the necessity for further development of new chelator-based PARP1 tracers with high binding affinity to enable the visualization of PARP1 changes in NASH pathology.

The aim of this study is to determine the factors affecting the CT attenuation of bone marrow, and its correlation with ¹⁸F-FDG uptake. The mean standardized uptake value (SUV) of vertebral bone marrow (Vertebral-SUV) and femoral bone marrow (Femoral-SUV) as well as CT number of bone marrow (BM-CT number) were measured in 243 patients who had undergone ¹⁸F-FDG PET/CT. The correlations among BM-CT number, Femoral-SUV, and Vertebral-SUV were investigated. The relationships of Femoral-SUV, Vertebral-SUV, and BM-CT number with blood parameters, age, blood sugar, and body weight were analyzed by correlation and multi-regression analyses. The Mann-Whitney U test and chi-square test and Binomial logistic analysis were used to examine the relationships between high BM-CT number (≥ 0 HU) and the above parameters. Significant correlations were observed between: BM-CT number and Femoral-SUV (r = 0.73, P < 0.01); Vertebral-SUV and Femoral-SUV (r = 0.78, P < 0.01); and BM-CT number and Vertebral-SUV (r = 0.52, P < 0.01). BM-CT number was correlated with patients' age in both univariable (r = -0.27) and multivariable analyses (β = -0.20). Positive BM-CT number correlated with WBC in both univariable (P = 0.04) and multivariable (P < 0.01) analyses. Bone marrow glucose metabolism had a tendency to decrease with age, was increased in patients with elevated CRP. In conclusion, CT attenuation of bone marrow correlated well with bone marrow metabolism and also tended to decrease with age. High bone marrow attenuation (≥ 0 HU) could predict elevated serum WBC.