American journal of nuclear medicine and molecular imaging最新文献

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.

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.

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.

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.

Breast cancer (BrCa) ranks as the most prevalent malignant neoplasm affecting women worldwide. The expression of programmed death-ligand 1 (PD-L1) in BrCa has recently emerged as a biomarker for immunotherapy response, but traditional immunohistochemistry (IHC)-based methods are hindered by spatial and temporal heterogeneity. Noninvasive and quantitative PD-L1 imaging using appropriate radiotracers can serve to determine PD-L1 expression in tumors. This study aims to demonstrate the viability of PET imaging with ⁶⁴Cu-labeled Durvalumab (abbreviated as Durva) to assess PD-L1 expression using a murine xenograft model of breast cancer. Durvalumab, a human IgG1 monoclonal antibody against PD-L1, was assessed for specificity in vitro in two cancer cell lines (MDA-MB-231 triple-negative breast cancer cell line and AsPC-1 pancreatic cancer cell line) with positive and negative PD-L1 expression by flow cytometry. Next, we performed the in vivo evaluation of ⁶⁴Cu-NOTA-Durva in murine models of human breast cancer by PET imaging and ex vivo biodistribution. Additionally, mice bearing AsPC-1 tumors were employed as a negative control. Tumor uptake was quantified based on a 3D region-of-interest (ROI) analysis of the PET images and ex vivo biodistribution measurements, and the results were compared against conventional IHC testing. The radiotracer uptake was evident in MDA-MB-231 tumors and showed minimal nonspecific binding, corroborating IHC-derived results. The results of the biodistribution showed that the MDA-MB-231 tumor uptake of ⁶⁴Cu-NOTA-Durva was much higher than ⁶⁴Cu-NOTA-IgG (a nonspecific radiolabeled IgG). In Conclusion, ⁶⁴Cu-labeled Durvalumab PET/CT imaging offers a promising, noninvasive approach to evaluate tumor PD-L1 expression.

Because carbon-11 (¹¹C) radiotracers cannot be shipped over long distances, their use in routine positron emission tomography (PET) studies is dependent on the production capabilities of individual radiochemistry laboratories. Since 2003, ¹¹C-labeled Pittsburgh compound B ([¹¹C]PiB) has been the gold standard PET radiotracer for in vivo imaging of amyloid β (Aβ) plaques. For more than two decades, researchers have been working to develop faster, higher-yielding, more robust, and optimized production methods with higher radiochemical yields for various imaging applications. This review evaluates progress in [¹¹C]PiB radiochemistry. An introductory overview assesses how it has been applied in clinical neurologic imaging research. We examine the varying approaches reported for radiolabeling, purification, extraction, and formulation. Further considerations for QC methods, regulatory considerations, and optimizations were also discussed.

Tumors are often with complex and heterogeneous biological processes, such as glycometabolism and fibrosis, which are the main biochemical pathways that determine therapeutic effects. Specifically, this study aims to assess the diagnosing performance of ¹⁸F-FDG and ⁶⁸Ga-FAPI-04 PET for different stages of progressive bone metastases with PSMA-negative pathology. Bone metastatic mouse model of prostate cancer was constructed via intra-bone injection of PSMA-negative prostate cancer PC3 cells. Cellular uptakes of ¹⁸F-FDG and ⁶⁸Ga-FAPI-04 were separately performed on PC3, NIH-3T3 (FAP-positive) and a mixture. ⁶⁸Ga-PSMA-11, ¹⁸F-FDG and ⁶⁸Ga-FAPI-04 PET/CT imaging were performed at 2, 4 weeks after tumor cell transplantation. Furthermore, PSMA and FAP expression in bone metastases were assessed by immunohistochemistry, and then compared with the imageological findings. On the cellular level, the independent tracer uptake on the basis of glycometabolism and fibrosis was observed. For animal imaging, ⁶⁸Ga-PSMA-11 imaging showed weak or absent tracer uptake in PSMA-negative bone metastatic lesions. In contrast, ⁶⁸Ga-FAPI-04 PET of bone metastases had a higher uptake and tumor-to-muscle (T/M) ratio than ¹⁸F-FDG PET that was relative steady during the observation, but T/M ratio of fibrosis gradually decreased with increasing tumor growth, which ranged from 5.11 ± 1.26 at 2 weeks to 3.54 ± 0.23 at 4 weeks, revealing the delayed formation of tumor stroma in rapid proliferation. In addition, PET imaging results were corroborated by immunohistochemical assessment. In conclusion, molecular imaging approach revealed the heterogeneous progression of tumor cells and tumor stroma of bone metastasis of prostate cancer, and further confirming the necessity of multi-molecular imaging in cancer imaging.

Objective: To investigate the value of ^99mTc-pertechnetate scan in postoperative differentiated thyroid cancer (DTC) patients with lymph node (LN) metastases (LNM) uptake ^99mTc-pertechnetate, especially the predictive value to their response to radioiodine-131 (¹³¹I) therapy.

Methods: This retrospective study collected 752 patients with DTC and LNM treated at Zhejiang Cancer Hospital between May 2012 and December 2017. Depending on the ability of LNM uptake ^99mTc-pertechnetate, the patients were grouped as the ^99mTc-pertechnetate-avid (n=88) vs. ^99mTc-pertechnetate-non-avid (n=664) groups. And Propensity score matching (PSM) was performed at a 1:4 ratio to reduce confounding bias.

Results: In the PSM analysis, the 1:4 matched cohort comprised 752 patients (88 with ^99mTc-pertechnetate-avid LNM, 664 with ^99mTc-pertechnetate-non-avid LNM). Patients' age, initial ¹³¹I activity and frequency of iodine therapy were included as covariates. After PSM analysis, 363 patients (^99mTc-pertechnetate-avid group, n=83; ^99mTc-pertechnetate-non-avid group, n=280) were successfully matched. Among the 363 PSM-matched patients, 48/83 (57.8%) in the ^99mTc-pertechnetate-avid group and 158/280 (56.4%) in the ^99mTc-pertechnetate-non-avid group had two or more ¹³¹I treatments. The nsTg and the percentage of changes in ssTg between the ^99mTc-pertechnetate-avid and ^99mTc-pertechnetate-non-avid groups were significantly different ([0.05 (0.04 to 0.90) vs. 0.40 (0.04 to 4.92), p=0.018] and [-88% (-98%, -50%) vs. -66% (-86%, -30%), p < 0.001], respectively). No significant differences were observed between the two groups in the other parameters (age, pathological type, distant metastasis, follow-up time, AJCC TNM stage, initial ¹³¹I treatment activity, and ¹³¹I treatment frequency) after PSM (all p > 0.05).

Conclusion: In patients with DTC and LNM, LNM uptake of ^99mTc-pertechnetate is a rare phenomenon. Patients with ^99mTc-pertechnetate-avid LNMs were more likely to benefit from ¹³¹I therapy, even after adjustment for age, ¹³¹I treatment frequency, and initial ¹³¹I activity.

Extranodal NK/T-cell lymphoma (ENKTL) is an uncommon subtype of non-Hodgkin's lymphoma that is closely related to Epstein-Barr virus (EBV) infection. ENKTL exhibits distinctive clinicopathological features among lymphomas and has poor overall survival in the absence of effective treatment. The timely and accurate diagnosis of ENKTL is crucial for effective treatment and a positive prognosis. ¹⁸F-Fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has emerged as an invaluable diagnostic modality for staging, curative effect evaluation, and prognosis analysis in ENKTL. We herein provide a comprehensive overview of the advances in the application of ¹⁸F-FDG PET/CT in patients with ENKTL.