Evaluation of [68Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis.
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SUBMITTER: Jahandideh A
PROVIDER: S-EPMC8714834 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIntegrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of 68Ga-NODAGA-RGD, a specific αvβ3 integrin ligand for PET.Materials and methodsThe data of 44 patients who underwent 68Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann-Whitney U test, Pearson correlation and Spearman correlation.Results68Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03-2.55] vs. 1.81 [1.56-1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04).Conclusions68Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis.
| S-EPMC8364589 | biostudies-literature
Project description:PurposeMultimeric arginine-glycine-aspartic acid (RGD) peptides have advantages for imaging integrin ?v?3 expression. Here, we compared the in vitro and in vivo behavior of three different Ga-68-labeled multimeric Fusarinine C-RGD (FSC-RGD) conjugates, whereby RGD was coupled directly, via a succinic acid or PEG linker (FSC(RGDfE)3, FSC(succ-RGD)3, FSC(Mal-RGD)3). The positron emission tomography/X-ray computed tomography (PET/CT) imaging properties were further compared using [(68)Ga]FSC(succ-RGD)3 with the monomeric [(68)Ga]NODAGA-RGD in a murine tumor model.ProcedureFSC-RGD conjugates were labeled with Ga-68, and stability properties were studied. For in vitro characterization, the partition coefficient, integrin ?v?3 binding affinity, and cell uptake were determined. To characterize the in vivo properties, biodistribution studies and microPET/CT were carried out using mice bearing either human M21/M21-L melanoma or human U87MG glioblastoma tumor xenografts.ResultsAll FSC-RGD conjugates were quantitatively labeled with Ga-68 within 10 min at RT. The [(68)Ga]FSC-RGD conjugates exhibited high stability and hydrophilic character, with only minor differences between the different conjugates. In vitro and in vivo studies showed enhanced integrin ?v?3 binding affinity, receptor-selective tumor uptake, and rapid renal excretion resulting in good imaging properties.ConclusionsThe type of linker between FSC and RGD had no pronounced effect on targeting properties of [(68)Ga]FSC-RGD trimers. In particular, [(68)Ga]FSC(succ-RGD)3 exhibited improved properties compared to [(68)Ga]NODAGA-RGD, making it an alternative for imaging integrin ?v?3 expression.
| S-EPMC5010584 | biostudies-literature
Project description:68Ga-NODAGA-exendin-4 is a promising tracer for β-cell imaging using PET/CT. Possible applications include preoperative visualization of insulinomas and discrimination between focal and diffuse forms of congenital hyperinsulinism. There is also a significant role for this tracer in extending our knowledge on the role of β-cell mass in the pathophysiology of type 1 and type 2 diabetes by enabling noninvasive quantification of tracer uptake as a measure for β-cell mass. Calculating radiation doses from this tracer is important to assess its safety for use in patients (including young children) with benign diseases and healthy individuals. Methods: Six patients with hyperinsulinemic hypoglycemia were included. After intravenous injection of 100 MBq of the tracer, 4 successive PET/CT scans were obtained at 30, 60, 120, and 240 min after injection. Tracer activity in the pancreas, kidneys, duodenum, and remainder of the body were determined, and time-integrated activity coefficients for the measured organs were calculated. OLINDA/EXM software, version 1.1, was applied to calculate radiation doses using the reference adult male and female models and to estimate radiation doses to children. Results: The mean total effective dose for adults was very low (0.71 ± 0.07 mSv for a standard injected dose of 100 MBq). The organ with the highest absorbed dose was the kidney (47.3 ± 10.2 mGy/100 MBq). The estimated effective dose was 2.32 ± 0.32 mSv for an injected dose of 20 MBq in newborns. This dose decreased to 0.77 ± 0.11 mSv/20 MBq for 1-y-old children and 0.59 ± 0.05 mSv for an injected dose of 30 MBq in 5-y-old children. Conclusion: Our human PET/CT-based dosimetric calculations show that the effective radiation doses from the novel tracer 68Ga-NODAGA-exendin-4 are very low for adults and children. The doses are lower than reported for other polypeptide tracers such as somatostatin analogs (2.1-2.6 mSv/100 MBq) and are beneficial for application as a research tool, especially when repeated examinations are needed.
| S-EPMC6954461 | biostudies-literature
Project description:Objective: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-associated myocarditis. Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n = 23) to three patients with suspected ICI-associated myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. All three patients' myocardial biopsies were examined for inflammatory cells. Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1,771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients' FAPI PET/CTs showed cardiac enrichment of the marker which was less distinct or absent in patients receiving ICIs without any signs of immunological adverse effects or cardiac impairment (n = 23) [Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)]. Conclusions: Apart from the successful implementation of ICIs in oncological treatments, ICI-associated myocarditis is still a challenging adverse effect. FAPI PET/CT may be used in order to identify affected patients at an early stage. Moreover, when integrated into cancer stage diagnostics, it contributes to cardiac risk stratification besides biomarker, ECG and echocardiography.
| S-EPMC7946849 | biostudies-literature
Project description:PurposeClinically non-functioning pituitary macroadenomas (NFMA) have been reported to express somatostatin receptors (SSTR), but results are inconsistent across different studies. This may be related to limited sensitivity and specificity of techniques used to date, i.e. immunohistochemistry in surgical specimens and 111In-DTPA-octreotide scintigraphy in vivo. The aim of this study was to assess SSTR expression in NFMA in vivo using 68Ga-DOTATATE PET, which offers superior sensitivity and spatial resolution as compared with planar scintigraphy or SPECT.MethodsThirty-seven patients diagnosed with NFMA underwent 68Ga-DOTATATE PET/CT of the head in the framework of a randomised controlled trial assessing the effect of the somatostatin analogue lanreotide on NFMA size. Individual co-registered T1-weighted pituitary MRIs were used to assess 68Ga-DOTATATE uptake (SUVmean) in the adenoma. An SUVmean of > 2 was considered positive.Results68Ga-DOTATATE uptake was positive in 34/37 patients (92%), with SUVmean of positive adenomas ranging from 2.1 to 12.4 (mean ± SD 5.8 ± 2.6).ConclusionsThis is the first report of 68Ga-DOTATATE PET performed in NFMA patients, demonstrating in vivo SSTR expression in the vast majority of cases. The high positivity rate when compared with results obtained with 111In-DTPA-octreotide scintigraphy probably reflects the superior sensitivity of PET imaging.Trial registrationNetherlands Trial Register, NL5136, registered on 18 August 2015; EudraCT, 2015-001234-22, registered on 10 March 2015, https://eudract.ema.europa.eu/.
| S-EPMC8218160 | biostudies-literature
Project description:BackgroundPositron emission tomography (PET) has the potential for visualization and quantification of gastric emptying (GE). The traditional Chinese medicine (TCM) has been recognized promising for constipation. This study aimed to establish a PET imaging method for noninvasive GE measurement and to evaluate the efficacy of a TCM on delayed GE caused by constipation using PET imaging.Methods[68Ga]Ga-NOTA was synthesized as the tracer and sesame paste with different viscosity were selected as test meals. The dynamic PET scans were performed after [68Ga]Ga-NOTA mixed with test meals were administered to normal mice. Two methods were utilized for the quantification of PET imaging. A constipation mouse model was treated with maren chengqi decoction (MCD), and the established PET imaging scans were performed after the treatment.Results[68Ga]Ga-NOTA was synthesized within 20 min, and its radiochemical purity was > 95%. PET images showed the dynamic process of GE. %ID/g, volume, and total activity correlated well with each other. Among which, the half of GE time derived from %ID/g for 4 test meals were 3.92 ± 0.87 min, 13.1 ± 1.25 min, 17.8 ± 1.31 min, and 59.7 ± 3.11 min, respectively. Constipation mice treated with MCD showed improved body weight and fecal conditions as well as ameliorated GE measured by [68Ga]Ga-NOTA PET.ConclusionsA PET imaging method for noninvasive GE measurement was established with stable radiotracer, high image quality, and reliable quantification methods. The efficacy of MCD on delayed GE was demonstrated using PET.
| S-EPMC7881688 | biostudies-literature
Project description:BackgroundProstate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [68Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.MethodsEligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[18F]FDG PET and/or 131I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [68Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[18F]FDG PET CT/MRI for lesion location and relative intensity.ResultsTwelve patients underwent [68Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[18F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[18F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.Conclusions[68Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[18F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.
| S-EPMC7581659 | biostudies-literature
Project description:Microbubble (MB) contrast agents have revolutionalised the way ultrasound (US) imaging can be used clinically and pre-clinically. Contrast-enhanced US offers improvements in soft-tissue contrast, as well as the ability to visualise disease processes at the molecular level. However, its inability to provide in vivo whole-body imaging can hamper the development of new MB formulations. Herein, we describe a fast and efficient method for achieving 68Ga-labelling of MBs after a direct comparison of two different strategies. The optimised approach produces 68Ga-labelled MBs in good yields through the bioorthogonal inverse-electron-demand Diel-Alder reaction between a trans-cyclooctene-modified phospholipid and a new tetrazine-bearing HBED-CC chelator. The ability to noninvasively study the whole-body distribution of 68Ga-labelled MBs was demonstrated in vivo using positron emission tomography (PET). This method could be broadly applicable to other phospholipid-based formulations, providing accessible solutions for in vivo tracking of MBs.
| S-EPMC6552490 | biostudies-literature
Project description:This study aims to further explore dynamic 68Ga-FAPI-04 PET/CT imaging of healthy Chinese subjects and lung cancer patients. Moreover, the variability of 68Ga-FAPI-04 uptake in normal organs was measured to provide a basis for analyzing its biological distribution, interpreting auxiliary images, determining the reliability of image quantification, and monitoring treatment. Six patients (3 subjects without tumors and 3 lung cancer patients) separately underwent 68Ga-FAPI-04 and 2-[18F]FDG PET/CT imaging within 1 week. The biodistribution and internal radiation dosimetry were reported and compared with data previously obtained from Caucasian patients. Moreover, the mean SUV (standardized uptake value) was normalized to body mass or to lean body mass (SUL), and the coefficients of variation (CVs) were calculated and compared for each volume of interest. The average whole-body effective dose was calculated to be 1.27E-02 mSv/MBq, which was comparable with previously reported results of 68Ga-FAPI-04 probes. Furthermore, the SUVmean was slightly higher than the SULmean in most organs; however, the CV of the SULmean for most organs was higher than that of the SUVmean at later time points. In the liver, the CV of the SUVmean was lower (12.7%) than that of the SULmean and was similar to the CV for corresponding 2-[18F]FDG PET/CT value (11.8%). In addition, 68Ga-FAPI-04 PET/CT showed good efficacy for diagnosing lung cancer patients in this study. A comparison of the radiation dosimetry obtained before from a Caucasian population demonstrated no clinically significant differences between these two populations after 68Ga-FAPI-04 injection. The variability in most organs was slightly lower for SUVmean than for SULmean, suggesting that SUVmean may be the preferable parameter for quantifying images obtained with 68Ga-FAPI-04. In addition, 68Ga-FAPI-04 PET/CT imaging is expected to be a promising tool for diagnosing lung cancer.
| S-EPMC7991833 | biostudies-literature
Project description:PURPOSE:As a major activator of transforming growth factor ? (TGF-?), the RGD receptor ?v?8-integrin is involved in pathogenic processes related to TGF-? dysregulation, such as tumor growth, invasion, and radiochemoresistance, metastasis and tumor cell stemness, as well as epithelial-mesenchymal transition. The novel positron emission tomography (PET) radiopharmaceutical Ga-68-Triveoctin for in vivo mapping of ?v?8-integrin expression might enhance the prognosis of certain tumor entities, as well as support and augment TGF-?-targeted therapeutic approaches. METHODS:Monomeric and trimeric conjugates of cyclo(GLRGDLp(NMe)K(pent-4-ynoic amide)) were synthesized by click chemistry (CuAAC), labeled with Ga-68, and evaluated in MeWo (human melanoma) xenografted SCID mice by means of PET and ex-vivo biodistribution. ?v?8-integrin expression in murine tissues was determined by ?8-IHC. A human subject received a single injection of 173 MBq of Ga-68-Triveoctin and underwent 3 subsequent PET/CT scans at 25, 45, and 90 min p.i.. RESULTS:The trimer Ga-68-Triveoctin exhibits a 6.7-fold higher ?v?8-integrin affinity than the monomer (IC50 of 5.7 vs. 38 nM, respectively). Accordingly, biodistribution showed a higher tumor uptake (1.9 vs. 1.0%IA/g, respectively) but a similar baseline upon blockade (0.25%IA/g for both). IHC showed an intermediate ?8-expression in the tumor while most organs and tissues were found ?8-negative. Low non-target tissue uptakes (<?0.4%IA/g) confirmed a low degree of unspecific binding. Due to its hydrophilicity (log D?=?-?3.1), Ga-68-Triveoctin is excreted renally and shows favorable tumor/tissue ratios in mice (t/blood: 6.7; t/liver: 6.8; t/muscle: 29). A high kidney uptake in mice (kidney-to-blood and -to-muscle ratios of 126 and 505, respectively) is not reflected by human PET (corresponding values are 15 and 30, respectively), which furthermore showed notable uptakes in coeliac and choroid plexus (SUVmean 6.1 and 9.7, respectively, 90 min p.i.). CONCLUSION:Ga-68-Triveoctin enables sensitive in-vivo imaging ?v?8-integrin expression in murine tumor xenografts. PET in a human subject confirmed a favorable biodistribution, underscoring the potential of Ga-68-Triveoctin for mapping of ?v?8-integrin expression in a clinical setting.
| S-EPMC7603442 | biostudies-literature