American journal of nuclear medicine and molecular imaging最新文献

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.

Alzheimer's disease (AD) is the most prevalent neurodegenerative condition. The definitive diagnosis of AD remains a post-mortem neuropathological study of the brain. Unfortunately, there are no established diagnostic criteria to achieve an accurate diagnosis of AD in a similarly objective fashion among living patients. Molecular imaging provides one way of enhancing clinical criteria where objective measures of AD correlate to the presence and progression of disease. In this article, the amyloid and tau hypotheses are considered with respect to pathological, imaging, and therapeutic studies. The value of beta-amyloid (Aβ) PET and tau PET are ascertained. Subsequently, the binding characteristics and quality of Aβ and tau tracers are explored. Finally, the value of Aβ and tau imaging in AD can be determined relevant from in-vivo studies of AD patients. Considering the evolving literature in AD and PET imaging, it has become clear that PET can play a role in the diagnosis and prognosis of AD. The use of Aβ imaging has been extensively studied with mixed results suggesting a limited clinical utility. Conversely, tau-PET has shown early success in similar applications as Aβ imaging. Specifically, we find that there is value in FDG-PET and prospective utility in tau-PET. Ultimately, the community must acknowledge that the role of Aβ imaging for diagnosing and managing AD is very limited and that FDG-PET will remain the study of choice at this time. Moreover, research efforts must continue to determine the prospective value of tau imaging to the assessment of this disease.

We measured changes in 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) images in the lung parenchyma to quantify the degree of lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT). The goal of this study was to demonstrate successful implementation of this imaging methodology on NSCLC patients and to report quantitative statistics between pre-RT and post-RT. Seventy-one patients with NSCLC underwent FDG-PET/CT imaging before and after RT in a prospective study (ACRIN 6668/RTOG 0235). Comparisons between pre-RT and post-RT PET/CT were conducted for partial volume corrected (PVC)-mean standardized uptake value (SUVmean), PVC-global lung parenchymal glycolysis (GLPG), and lung volume for both ipsilateral and contralateral lungs using the nonparametric Wilcoxon signed-rank test. Regression modeling was conducted to associate clinical characteristics with post-RT PET/CT parameters. There was a significant increase in average SUVmean and GLPG of the ipsilateral lung (relative change 40% and 20%) between pre-RT and post-RT PET/CT scans (P<0.0001 and P=0.004). Absolute increases in PVC-SUVmean and PVC-GLPG were more pronounced (ΔPVC-SUVmean 0.32 versus ΔSUVmean 0.28; ΔPVC-GLPG 463.34 cc versus ΔGLPG 352.90 cc) and highly significant (P<0.0001). In contrast, the contralateral lung demonstrated no significant difference between pre-RT to post-RT in either GLPG (P=0.12) or SUVmean (P=0.18). The only clinical feature significantly associated with post-RT PET/CT parameters was clinical staging. Our study demonstrated inflammatory response in the ipsilateral lung of NSCLC patients treated with photon RT, suggesting that PET/CT parameters may serve as biomarkers for radiation pneumonitis (RP).

The blood-brain barrier (BBB) is usually impermeable to several drugs, which hampers treatment of various brain-related diseases/disorders. There have been several approaches to open the BBB, including intracarotid infusion of hyperosmotic concentrations of arabinose, mannitol, oleic or linoleic acids, or alkylglycerols, intravenous infusion of bradykinin B2, administration of a fragment of the ZO toxin from vibrio cholera, targeting specific components of the tight junctions (e.g. claudin-5) with siRNA or novel peptidomimetic drugs, or the use of ultrasound with microbubbles. We propose the use of a low molecular weight (MW), nitrone-type compound, OKN-007, which can temporarily open up the BBB for 1-2 hours. Gadolinium (Gd)-based compounds assessed ranged in MW from 546 (Gd-DTPA) to 465 kDa (β-galactosidase-Gd-DOTA). We also included an albumin-based CA (albumin-Gd-DTPA-biotin) for assessment, as well as an antibody (Ab) against a neuron-specific biomarker conjugated to Gd-DOTA (anti-EphB2-Gd-DOTA). For the anti-EphB2 (goat Ab)-Gd-DOTA assessment, we utilized an anti-goat Ab conjugated with horse radish peroxidase (HRP) for confirmation of the presence of the anti-EphB2-Gd-DOTA probe. In addition, a Cy5 labeled anti-EphB2 Ab was co-administered with the anti-EphB2-Gd-DOTA probe, and assessed ex vivo. This study demonstrates that OKN-007 may be able to temporarily open up the BBB to augment the delivery of various compounds ranging in MW from as small as ~550 to as large as ~470 kDa. This compound is an investigational new drug for glioblastoma (GBM) therapy in clinical trials. The translational capability for human use to augment the delivery of non-BBB-permeable drugs is extremely high.

FACBC (anti-1-amino-3-¹⁸F-fluorocyclobutane-1-carboxylic acid) is a FDA-approved PET-tracer in patients with suspected recurrent prostate cancer. In the diagnostic work-up of primary prostate cancer, accurate localization of the index tumor is needed for image-guidance of biopsies. We therefore assessed the performance of FACBC PET/CT to detect and localize the index tumor and compared it to multiparametric MRI (mpMRI) using whole-mount histopathology as reference standard. Twenty-three patients with biopsy-proven prostate cancer had FACBC PET/CT and mpMRI within two weeks prior to prostatectomy. FACBC PET/CT was acquired as 14 minutes list-mode and re-binned into seven 2-minutes intervals. Static FACBC was the acquired data from 4-6 minutes, whereas the dynamic FACBC included all seven intervals. Two radiologists and two nuclear medicine physicians independently interpreted the images and consensus was reached in case of discrepancy. Static PET detected 15 of 23 (65%) of the index tumors, dynamic PET detected 14 of 22 (64%), and MRI detected 20 of 23 (87%). To assess the extent of the tumor, the interpreters delineated the tumor in a 12-regions sector-based template. True positive, true negative, false positive and false negative sectors were recorded based on the template drawings and whole-mount histopathology. Both static and dynamic FACBC PET had sensitivity of 40% and specificity of 99%, whereas MRI had sensitivity of 81% and specificity of 100%. Our data indicate that FACBC PET/CT may be useful but that mpMRI is better for localizing the index tumor in patients with prostate cancer.