American journal of nuclear medicine and molecular imaging最新文献

While reduced global brain metabolism is known in aging, Alzheimer's disease (AD), small vessel disease (SVD) and delirium, explanation of regional brain metabolic (rBM) changes is a challenge. We hypothesized that this may be explained by "triage phenomenon", to preserve metabolic supply to vital brain areas. We studied changes in rBM in 69 patients with at least 5% decline in global brain metabolism during active lymphoma. There was significant decline in the rBM of the inferior parietal, precuneus, superior parietal, lateral occipital, primary visual cortices (P<0.001) and in the right lateral prefrontal cortex (P=0.01). Some areas showed no change; multiple areas had significantly increased rBM (e.g. medial prefrontal, anterior cingulate, pons, cerebellum and mesial temporal cortices; P<0.001). We conclude the existence of a physiological triage phenomenon and argue a new hypothetical model to explain the shared events in the pathophysiology of aging, AD, SVD and delirium.

Macromolecular crystallography is commonly used to determine the structure of biological macromolecules. Currently the beamlines at synchrotron radiation facilities play an important role in macromolecular crystallography, and have produced an enormous number of molecular structures to help solve scientific questions and support applications. Structure information makes significant contributions to the virus-related research as well. However, it is mandatory to be protected the operators under a compatible biosafety infrastructure when a pathological agent is set up in a beamline. Here a level-2 biosafety protection for a macromolecular crystallography beamline at Shanghai Synchrotron Radiation Facility (SSRF) is introduced. To fulfill the biosafety in a radioactive environment, a dedicated design is implemented. Since the beamline will be opened to the external users from nationwide research units, the management process and experimental method are also drawn up.

Lutetium-177 [T½ = 6.76 d; E_β (max) = 0.497 MeV; maximum tissue range ~2.5 mm; 208 keV γ-ray] is one of the most important theranostic radioisotope used for the management of various oncological and non-oncological disorders. The present review chronicles the advancement in the last decade in ¹⁷⁷Lu-radiopharmacy with a focus on ¹⁷⁷Lu produced via direct ¹⁷⁶Lu (n, γ) ¹⁷⁷Lu nuclear reaction in medium flux research reactors. The specific nuances of ¹⁷⁷Lu production by various routes are described and their pros and cons are discussed. Lutetium, is the last element in the lanthanide series. Its chemistry plays a vital role in the preparation of a wide variety of radiopharmaceuticals which demonstrate appreciable in vivo stability. Traditional bifunctional chelators (BFCs) that are used for ¹⁷⁷Lu-labeling are discussed and the upcoming ones are highlighted. Research efforts that resulted in the growth of various ¹⁷⁷Lu-based radiopharmaceuticals in preclinical and clinical settings are provided. This review also summarizes the results of clinical studies with potent ¹⁷⁷Lu-based radiopharmaceuticals that have been prepared using medium specific activity ¹⁷⁷Lu produced by direct neutron activation route in research reactors. Overall, the review amply demonstrates the practicality of the medium specific activity ¹⁷⁷Lu towards formulation of various clinically useful radiopharmaceuticals, especially for the benefit of millions of cancer patients in developing countries with limited reactor facilities.

The present study determined the optimal timing of scanning for measurement of cerebral blood flow (CBF) after acetazolamide (ACZ) administration for detection of preexisting cerebral hemodynamics and metabolism in bilateral major cerebral artery steno-occlusive diseases. Thirty three patients underwent ¹⁵O gas positron emission tomography (PET) and each parameter was obtained in the bilateral middle cerebral artery (MCA) territories. CBF was also obtained using H₂ ¹⁵O PET scanning performed at baseline and at 5, 15, and 30 min after ACZ administration. Relative CBF at each time point after ACZ administration to baseline CBF was calculated. For MCA territories with normal cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO₂), CBF continued increasing until 15 min after ACZ administration. For MCA territories with abnormally increased CBV, CBF decreased 5 min after ACZ administration. After that, CBF continued increasing until 30 min after ACZ administration. For MCA territories with abnormally decreased CMRO₂, CBF did not change 5 min after ACZ administration. Ten min later, CBF increased. The accuracy to detect abnormally increased CBV was significantly greater for relative CBF₅ than for relative CBF₁₅. The accuracy to detect abnormally decreased CMRO₂ was significantly greater for relative CBF₅ or CBF₁₅ than for relative CBF₃₀. For detecting abnormally increased oxygen extraction fraction, the accuracy did not differ among each relative CBF. These findings suggested that CBF measurement at 5 min after ACZ administration is the optimal timing for detection of preexisting cerebral hemodynamics and metabolism in bilateral major cerebral artery steno-occlusive diseases.

Several radiopharmaceuticals targeting fibroblast activation protein (FAP) based on the highly potent FAP inhibitor UAMC1110 are currently under investigation. Pre-clinical as well as clinical research exhibited the potential of these imaging agents. However, the monomeric small molecules seemed to have a short retention time in the tumor in combination with fast renal clearance. Therefore, our strategy was to develop homodimeric systems having two FAP inhibitors to improve residence time and tumor accumulation. The homodimers with two squaramide coupled FAP inhibitor conjugates DOTA.(SA.FAPi)₂ and DOTAGA.(SA.FAPi)₂ were synthesized and radiochemically evaluated with gallium-68. [⁶⁸Ga]Ga-DOTAGA.(SA.FAPi)₂ was tested for its in vitro stability, lipophilicity and affinity properties. In addition, human PET/CT scans were performed for [⁶⁸Ga]Ga-DOTAGA.(SA.FAPi)₂ with a head-to-head comparison with [⁶⁸Ga]Ga-DOTA.SA.FAPi and [¹⁸F]FDG. Labeling with gallium-68 demonstrated high radiochemical yields. Inhibition measurements revealed excellent affinity and selectivity with low nanomolar IC₅₀ values for FAP. In PET/CT human studies, significantly higher tumor uptake as well as longer tumor retention could be observed for [⁶⁸Ga]Ga-DOTAGA.(SA.FAPi)₂ compared to [⁶⁸Ga]Ga-DOTA.SA.FAPi. Therefore, the introduction of the dimer led to an advance in human PET imaging indicated by increased tumor accumulation and prolonged retention times in vivo and thus, the use of dimeric structures could be the next step towards prolonged uptake of FAP inhibitors resulting in radiotherapeutic analogs of FAP inhibitors.

Introduction: Evaluation of glomerular filtration rate is very important in both preclinical and clinical setting, especially in the context of chronic kidney disease. It is typically performed using ⁵¹Cr-EDTA or by imaging with ¹²³I-Hippuran scintigraphy, which has a significantly lower resolution and sensitivity as compared to PET. ⁶⁸Ga-EDTA represents a valid alternative due to its quick availability using a ⁶⁸Ge/⁶⁸Ga generator, while PET/CT enables both imaging of renal function and accurate quantitation of clearance of activity from both plasma and urine. Therefore, we aimed at investigating the use of ⁶⁸Ga-EDTA as a preclinical tracer for determining renal function in a knock-in rat model known to present progressive decline of renal function.

Methods: ⁶⁸Ga-EDTA was injected in 23 rats, either wild type (n=10) or knock-in (n=13). By applying a unidirectional, two-compartment model and Rutland-Patlak Plot linear regression analysis, split renal function was determined from the age of 6 weeks to 12 months.

Results: Glomerular filtration ranged from 0.025±0.01 ml/min at 6 weeks to 0.049±0.05 ml/min at 6 months in wild type rats. Glomerular filtration was significantly lower in knock-in rats at 6 and 12 months (P<0.01). No significant difference was observed in renal volumes between knock-in and wild type animals, based on imaging-derived volume calculations.

Conclusions: ⁶⁸Ga-EDTA turned out to be a very promising PET/CT tracer for the evaluation of split renal function. This method allowed detection of progressive renal impairment in a knock-in rat model. Additional validation in a human cohort is warranted to further assess clinical utility in both, healthy individuals and patients with renal impairment.

Radionuclide-labeled fibroblast activation protein inhibitors (FAPIs) are popular nuclear imaging probes in recent years. It's of great significance for tumor diagnosis and has great potential in tumor treatment. However, optimization of the probes is needed to further increase tumor uptake and prolong tumor retention for improved treatment efficacy and fewer side effects. In this issue of AJNMMI, Moon et al. reported two squaramide coupled FAPI conjugates (DOTA.(SA.FAPi)₂ and DOTAGA.(SA.FAPi)₂) and labeled them with ⁶⁸Ga. The resulted tracers showed increased tumor accumulation and persistent retention, which led to an advance in PET imaging. The use of dimeric structures provides a feasible strategy to develop radiotherapeutic analogs of FAP inhibitors.

The relationship between higher variant allele fraction (VAF) of genomic alterations in circulating tumor DNA (%ctDNA), an indicator of poor outcome, and maximum standardized uptake value (SUV_max), the most commonly used semi-quantitative parameter in ¹⁸F-FDG PET/CT, has not been studied. Overall, 433 cancer patients had blood-based next generation sequencing. Maximum and sum of %ctDNA alterations (%ctDNA_max and %ctDNA_sum, respectively) represent the maximum and sum of VAF, reported as a percentage. The subset of 46 eligible patients had treatment-naïve metastatic disease and PET/CT imaging, with median 13 days prior to ctDNA testing. We found a linear correlation between the maximum VAF (%ctDNA_max) (as well as the sum of the VAFs (%ctDNA_sum)) and SUV_max of the most ¹⁸F-FDG-avid lesion (r=0.43, P=0.003; r=0.43, P=0.002; respectively). Our data suggest that SUV_max may be a non-invasive and readily available surrogate indicator for %ctDNA, a prognostic factor for patient survival. Since higher %ctDNA has been previously correlated with worse outcome, the relationship between SUV_max, %ctDNA and survival warrants further study.

Quantification of tumor uptake using PET imaging is important for the evaluation of therapy response. For ¹⁸F FDG PET scans, a change in uptake of 25% is commonly considered significant. For scans using novel radiopharmaceuticals, the threshold of significance is unclear. Factors including imaging time, tumor size, activity concentration, and radiopharmaceutical may affect the repeatablity of uptake metrics. This work evaluates the effect of these parameters on the repeatablity of maximum SUV (SUV_max) and mean SUV (SUV_mean) in phantoms using ¹⁸F and ⁶⁸Ga. An Esser PET phantom (Data Spectrum, Durham NC) was scanned on a Biograph Horizon PET/CT scanner (Siemens Medical Solutions, Malvern PA) using ¹⁸F and ⁶⁸Ga. Data were acquired for 5 minutes with reconstructions between 0.5-5 minutes. The background activity mimicked clinical scans with target-to-background (T/B) ratios from 1.7-19.8. The SUV_max and SUV_mean were measured for 5 slices. The mean, standard deviation, and coefficient of variation (COV) were calculated. The effects of radionuclide, imaging time, activity concentration, and target size on COV were evaluated using multivariate gamma regressions. COV for ⁶⁸Ga was 40% higher and 54% higher on average than for ¹⁸F for SUV_max and SUV_mean, respectively. Decreased lesion size, imaging time, and activity concentration were significantly associated with increased COV for both metrics (P < 0.001). COV was substantially reduced at high T/B for ⁶⁸Ga. At the highest T/B the COV for SUV_max and SUV_mean was within the typical range seen for ¹⁸F. COV is relatively high for small targets (8 mm) but is dramatically reduced with high radiotracer uptake.

¹⁸F-FDG PET/CT can provide quantitative characterization with prognostic value for mantle cell lymphoma (MCL). However, detection of MCL is performed manually, which is labor intensive and not a part of the routine clinical practice. This study investigates a deep learning convolutional neural network (DLCNN) for computer-aided detection of MCL on ¹⁸F-FDG PET/CT. We retrospectively analyzed 142 baseline ¹⁸F-FDG PET/CT scans of biopsy-confirmed MCL acquired between May 2007 and October 2018. Of the 142 scans, 110 were from our institution and 32 were from outside institutions. An Xception-based U-Net was constructed to classify each pixel of the PET/CT images as MCL or not. The network was first trained and tested on the within-institution scans by applying five-fold cross-validation. Sensitivity and false positives (FPs) per patient were calculated for network evaluation. The network was then tested on the outside-institution scans, which were excluded from network training. For the 110 within-institution patients (85 male; median age, 58 [range: 39-84] years), the network achieved an overall median sensitivity of 88% (interquartile range [IQR]: 25%) with 15 (IQR: 12) FPs/patient. Sensitivity was dependent on lesion size and SUV_max but not on lesion location. For the 32 outside-institution patients (24 male; median age, 59 [range: 40-67] years), the network achieved a median sensitivity of 84% (IQR: 24%) with 14 (IQR: 10) FPs/patient. No significant performance difference was found between the within and outside institution scans. Therefore, DLCNN can potentially help with MCL detection on ¹⁸F-FDG PET/CT with high sensitivity and limited FPs.