Molecular Imaging最新文献

Background: Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases.

Objectives: To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors.

Methods: TTU was observed in RKO model on Cerenkov luminescence (CL) and near-infrared fluorescence (NIRF) imaging of radionuclide ¹³¹I or NIRF dyes labeled Atezolizumab and IgG. A mixture of NIRF dyes labeled Atezolizumab and ¹³¹I-labeled IgG was injected, and TTU was observed in the RKO and HCT8 model by NIRF/CL dual-modality in-situ imaging. TTU were observed by ¹³¹I-labeled Atezolizumab and IgG in-vitro distribution.

Results: Labeled IgG concentrated more in tumors than Atezolizumab. NIRF/CL imaging in 24 to 168 h showed that TTU gradually decreased over time, which decreased more slowly on CL imaging compared to NIRF imaging. The distribution data in-vitro showed that TTU of ¹³¹I-labeled IgG was higher than that of ¹³¹I-labeled Atezolizumab at any time point.

Conclusion: Non-specific IgG may not be suitable as a control for Atezolizumab in comparing tumor PD-L1 expression in nude mice via labeled antibody optical imaging under certain circumstances.

Objective: To investigate the performance of diffusion-tensor imaging (DTI) and hydrogen proton magnetic resonance spectroscopy (¹H-MRS) parameters in predicting the immunohistochemistry (IHC) biomarkers of glioma.

Methods: Patients with glioma confirmed by pathology from March 2015 to September 2019 were analyzed, the preoperative DTI and ¹H-MRS images were collected, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), in the lesion area were measured, the relative values relative ADC (rADC) and relative FA (rFA) were obtained by the ratio of them in the lesion area to the contralateral normal area. The peak of each metabolite in the lesion area of ¹H-MRS image: N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), and metabolite ratio: NAA/Cho, NAA/(Cho + Cr) were selected and calculated. The preoperative IHC data were collected including CD34, Ki-67, p53, S-100, syn, vimentin, NeuN, Nestin, and glial fibrillary acidic protein.

Results: One predicting parameter of DTI was screened, the rADC of the Ki-67 positive group was lower than that of the negative group. Two parameters of ¹H-MRS were found to have significant reference values for glioma grades, the NAA and Cr decreased as the grade of glioma increased, moreover, Ki-67 Li was negatively correlated with NAA and Cr.

Conclusion: NAA and Cr have potential application value in predicting glioma grades and tumor proliferation activity. Only rADC has predictive value for Ki-67 expression among DTI parameters.

Chimeric antigen receptor (CAR)-T cell-based immunotherapy has emerged as a path-breaking strategy for certain hematological malignancies. Assessment of the response to CAR-T therapy using quantitative imaging techniques such as positron emission tomography/computed tomography (PET/CT) has been broadly investigated. However, the definitive role of PET/CT in CAR-T therapy remains to be established. [¹⁸F]FDG PET/CT has demonstrated high sensitivity and specificity for differentiating patients with a partial and complete response after CAR-T therapy in lymphoma. The early therapeutic response and immune-related adverse effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome can also be detected on [¹⁸F]FDG PET images. In otherwise asymptomatic lymphoma patients with partial response following CAR-T therapy, the only positive findings could be abnormal PET/CT results. In multiple myeloma, a negative [¹⁸F]FDG PET/CT after receiving B-cell maturation antigen-directed CAR-T therapy has been associated with a favorable prognosis. In leukemia, [¹⁸F]FDG PET/CT can detect extramedullary metastases and treatment responses after therapy. Hence, PET/CT is a valuable imaging tool for patients undergoing CAR-T therapy for pretreatment evaluation, monitoring treatment response, assessing safety, and guiding therapeutic strategies. Developing guidelines with standardized cutoff values for various PET parameters and tumor cell-specific tracers may improve the efficacy and safety of CAR-T therapy.

This meeting report summarizes a consultants meeting that was held at International Atomic Energy Agency Headquarters, Vienna, in July 2022 to provide an update on the development of multimodality imaging by combining nuclear medicine imaging agents with other nonradioactive molecular probes and/or biomedical imaging techniques.

[¹⁸F]SynVesT-1 is a PET radiopharmaceutical that binds to the synaptic vesicle protein 2A (SV2A) and serves as a biomarker of synaptic density with widespread clinical research applications in psychiatry and neurodegeneration. The initial goal of this study was to concurrently conduct PET imaging studies with [¹⁸F]SynVesT-1 at our laboratories. However, the data in the first two human PET studies had anomalous biodistribution despite the injected product meeting all specifications during the prerelease quality control protocols. Further investigation, including imaging in rats as well as proton and carbon 2D-NMR spectroscopic studies, led to the discovery that a derivative of the precursor had been received from the manufacturer. Hence, we report our investigation and the first-in-human study of [¹⁸F]SDM-4MP3, a structural variant of [¹⁸F]SynVesT-1, which does not have the requisite characteristics as a PET radiopharmaceutical for imaging SV2A in the central nervous system.

Amyotrophic lateral sclerosis (ALS) is a disease leading to progressive motor degeneration and ultimately death. It is a complex disease that can take a significantly long time to be diagnosed, as other similar pathological conditions must be ruled out for a definite diagnosis of ALS. Noninvasive imaging of ALS has shed light on disease pathology and altered biochemistry in the ALS brain. Other than magnetic resonance imaging (MRI), two types of functional imaging, positron emission tomography (PET) and single photon emission computed tomography (SPECT), have provided valuable data about what happens in the brain of ALS patients compared to healthy controls. PET imaging has revealed a specific pattern of brain metabolism through [¹⁸F]FDG, while other radiotracers have uncovered neuroinflammation, changes in neuronal density, and protein aggregation. SPECT imaging has shown a general decrease in regional cerebral blood flow (rCBF) in ALS patients. This educational review summarizes the current state of ALS imaging with various PET and SPECT radiopharmaceuticals to better understand the pathophysiology of ALS.

Synaptic density in the central nervous system can be measured in vivo using PET with [¹⁸F]SynVesT-1. While [¹⁸F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson's disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [¹⁸F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [¹⁸F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential (BP_ND) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with k₂' fixed to either a sample average value (0.037 min^-1) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux (ps > 0.47). Each fitting method produced BP_ND estimates in close agreement with those derived from the 1TCM (subject R²s > 0.98, bias < 10%), with no difference in bias between the control and PD groups. With SRTM2, BP_ND estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans (bias < 6%). While these are preliminary results from a small sample of patients with PD (n = 5), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [¹⁸F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.

Purpose: Quantitative in vivo [¹⁸F]-(2S,4R)4-fluoroglutamine ([¹⁸F]4-FGln or more simply [¹⁸F]FGln) metabolic kinetic parameters are compared with activity levels of glutamine metabolism in different types of hepatocellular carcinoma (HCC).

Methods: For this study, we used two transgenic mouse models of HCC induced by protooncogenes, MYC, and MET. Biochemical data have shown that tumors induced by MYC have increased levels of glutamine metabolism compared to those induced by MET. One-hour dynamic [¹⁸F]FGln PET data were acquired and reconstructed for fasted MYC mice (n = 11 tumors from 7 animals), fasted MET mice (n = 8 tumors from 6 animals), fasted FVBN controls (n = 8 normal liver regions from 6 animals), nonfasted MYC mice (n = 16 tumors from 6 animals), and nonfasted FVBN controls (n = 8 normal liver regions from 3 animals). The influx rate constants (K ₁) using the one-tissue compartment model were derived for each tumor with the left ventricular blood pool input function.

Results: Influx rate constants were significantly higher for MYC tumors (K ₁ = 0.374 ± 0.133) than for MET tumors (K ₁ = 0.141 ± 0.058) under fasting conditions (P = 0.0002). Rate constants were also significantly lower for MET tumors (K ₁ = 0.141 ± 0.135) than normal livers (K ₁ = 0.332 ± 0.179) under fasting conditions (P = 0.0123). Fasting conditions tested for MYC tumors and normal livers did not result in any significant difference with P values > 0.005.

Conclusion: Higher influx rate constants corresponded to elevated levels of glutamine metabolism as determined by biochemical assays. The data showed that there is a distinctive difference in glutamine metabolism between MYC and MET tumors. Our study has demonstrated the potential of [¹⁸F]FGln PET imaging as a tool to assess glutamine metabolism in HCC tumors in vivo with a caution that it may not be able to clearly distinguish HCC tumors from normal liver tissue.