EJNMMI Research最新文献

Background: Dual-phase fluorine-18 labeled N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) positron emission tomography (PET) scans could be used to support disorders like Parkinson's disease (PD). Dopamine transporter (DAT) binding and cerebral perfusion are associated with ageing and gender. We investigated the effects of age and gender on non-degenerative parkinsonism, using automated quantification in striatum: specific binding ratios (SBRs) for DAT binding in delayed phase PET (dCIT) and standardized-uptake-value ratios (SUVRs) for cerebral perfusion in early phase PET (eCIT). We also examined the correlations between SBR and SUVR.

Methods: This retrospective study analyzed subjects with dual-phase ¹⁸F-FP-CIT PET scans. The eCIT images were acquired immediately post-injection, and dCIT images were taken 120 min later. With Brightonix software, automated quantification of SBRs for dCIT and SUVRs for eCIT were acquired from visually normal scans. The effects of aging and gender were assessed by regressing SBRs and SUVRs on age for both genders. The correlations between SUVRs and SBRs were evaluated.

Results: We studied 79 subjects (34 males and 45 females). An age-related reduction in SBRs was observed in the dorsal striatum, ventral striatum, caudate nucleus, and putamen for both genders. SUVRs were found to negatively correlate with age in the dorsal striatum, ventral striatum, caudate nucleus, and putamen for males and in the dorsal striatum and caudate nucleus for females. Positive correlations between SBRs and SUVRs in the dorsal striatum, ventral striatum, caudate nucleus, and putamen for male and in the dorsal striatum, caudate nucleus, and putamen for females.

Conclusions: Using quantified values from dual-phase ¹⁸F-FP-CIT PET with a single injection, we demonstrate a negative impact of age on SBRs (DAT binding) in the striatum for both genders and SUVRs (cerebral perfusion) in the dorsal striatum and caudate nucleus for both genders and in the ventral striatum and putamen for males. Additionally, we found positive associations between SBR and SUVR values in the dorsal striatum, caudate nucleus, and putamen for both genders and in the ventral striatum for males.

Background: Positron emission tomography (PET) is now an established diagnostic method for myocardial perfusion imaging (MPI) in coronary artery disease, which is the main cause of death globally. The available tracers show several limitations, therefore, the ¹⁸F-labelled tracer is in high demand nowadays. The preclinical studies on normal Wistar rats aimed to characterise two potential, novel radiotracers, [¹⁸F]SYN1 and [¹⁸F]SYN2, to evaluate which is a better candidate for PET MPI cardiotracer.

Results: The dynamic microPET images showed rapid myocardial uptake for both tracers. However, the uptake was higher and also stable for [¹⁸F]SYN2, with an average standardized uptake value of 3.8. The biodistribution studies confirmed that [¹⁸F]SYN2 uptake in the cardiac muscle was high and stable (3.02%ID/g at 15 min and 2.79%ID/g at 6 h) compared to [¹⁸F]SYN1 (1.84%ID/g at 15 min and 0.32%ID/g at 6 h). The critical organs determined in dosimetry studies were the small intestine and the kidneys. The estimated effective dose for humans was 0.00714 mSv/MBq for [¹⁸F]SYN1 and 0.0109 mSv/MBq for [¹⁸F]SYN2. The tested dose level of 2 mg/kg was considered to be the No Observed Adverse Effect Level (NOAEL) for both candidates. The better results were achieved for [¹⁸F]SYN2, therefore, further preclinical studies were conducted only for this tracer. Radioligand binding assays showed significant responses in 3 from 68 assays: muscarinic acetylcholine M₁ and M₂ receptors and potassium channel hERG. The compound was mostly metabolised via an oxidative N-dealkylation, while the fluor substituent was not separated from the molecule.

Conclusion: [¹⁸F]SYN2 showed a favourable pharmacodynamic and pharmacokinetic profile, which enabled a clear visualization of the heart in microPET. The compound was well-tolerated in studies in normal rats with moderate radiation exposure. The results encourage further exploration of [¹⁸F]SYN2 in clinical studies.

Background: Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [¹⁸F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [¹⁸F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [¹⁸F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [¹⁸F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [¹⁸F]AlF-NOTA-PRGD2 and ¹⁸F-labelled fluorodeoxyglucose ([¹⁸F]FDG) PET imaging in UM xenografts and UM patients were conducted.

Results: The in vitro data showed that [¹⁸F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [¹⁸F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [¹⁸F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [¹⁸F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [¹⁸F]FDG tracer.

Conclusion: [¹⁸F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [¹⁸F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [¹⁸F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis.

Trial registration: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .

Background: Subtype diagnosis of primary aldosteronism (PA) is used to determine treatment, and the potential utility of ⁶⁸Ga-pentixafor PET/CT for investigation of PA has long been recognized. The study aimed to evaluate the clinical value of ⁶⁸Ga-pentixafor PET/CT in the diagnosis and prognosis of patients with bilateral lesions identified by CT.

Methods: In total, 25 patients with PA and bilateral lesions on CT were retrospectively evaluated. All patients underwent ⁶⁸Ga-Pentixafor PET/CT and adrenal vein sampling. The analysis focused on establishing the relationship between bilateral adrenal lesions SUVmax and the ratio of bilateral adrenal lesions SUVmax (CON) and clinical diagnosis, treatment outcomes, and KCNJ5 gene status.

Results: The concordance rate between ⁶⁸Ga-Pentixafor PET/CT and adrenal venous sampling was 65.2% (15/23). The lateralization results of ⁶⁸Ga-pentixafor PET/CT supported the clinical decisions of 20 patients with PA, 90% of whom showed effectiveness in treatment. The SUVmax on the dominant side of the surgically treated patients was higher than that of patients treated with drugs. The SUVmax of the KCNJ5 mutant group was higher than that of the KCNJ5 wild group, and ⁶⁸Ga-Pentixafor uptake was correlated with KCNJ5 gene status.

Conclusions: ⁶⁸Ga-Pentixafor PET/CT proves beneficial for patients with PA with bilateral lesions on CT. The treatment is generally effective based on the results of PET lateralization. Simultaneously, a certain relationship exists between ⁶⁸Ga-Pentixafor PET/CT and KCNJ5 gene status, warranting further analysis.

Background: The aim of this study is to investigate the added value of combining tumour blood flow (BF) and metabolism parameters, including texture features, with clinical parameters to predict, at baseline, the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with newly diagnosed breast cancer (BC).

Methods: One hundred and twenty-eight BC patients underwent a ¹⁸F-FDG PET/CT before any treatment. Tumour BF and metabolism parameters were extracted from first-pass dynamic and delayed PET images, respectively. Standard and texture features were extracted from BF and metabolic images. Prediction of pCR was performed using logistic regression, random forest and support vector classification algorithms. Models were built using clinical (C), clinical and metabolic (C+M) and clinical, metabolic and tumour BF (C+M+BF) information combined. Algorithms were trained on 80% of the dataset and tested on the remaining 20%. Univariate and multivariate features selections were carried out on the training dataset. A total of 50 shuffle splits were performed. The analysis was carried out on the whole dataset (HER2 and Triple Negative (TN)), and separately in HER2 (N=76) and TN (N=52) tumours.

Results: In the whole dataset, the highest classification performances were observed for C+M models, significantly (p-value<0.01) higher than C models and better than C+M+BF models (mean balanced accuracy of 0.66, 0.61, and 0.64 respectively). For HER2 tumours, equal performances were noted for C and C+M models, with performances higher than C+M+BF models (mean balanced accuracy of 0.64, and 0.61 respectively). Regarding TN tumours, the best classification results were reported for C+M models, with better performances than C and C+M+BF models but not significantly (mean balanced accuracy of 0.65, 0.63, and 0.62 respectively).

Conclusion: Baseline clinical data combined with global and texture tumour metabolism parameters assessed by ¹⁸F-FDG PET/CT provide a better prediction of pCR after NAC in patients with BC compared to clinical parameters alone for TN, and HER2 and TN tumours together. In contrast, adding BF parameters to the models did not improve prediction, regardless of the tumour subgroup analysed.

Background: N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT), the representative cocaine derivative used in dopamine transporter imaging, is a promising biomarker, as it reflects the severity of Parkinson's disease (PD). ¹²³I- and ¹⁸F-labeled FP-CIT has been used for PD diagnosis. However, preclinical studies evaluating [¹⁸F]FP-CIT as a potential diagnostic biomarker are scarce. Among translational research advancements from bench to bedside, translating preclinical findings into clinical practice is one-directional. The aim of this study is to employ a circular approach, beginning back from the preclinical stage, progressing to the supplementation of [¹⁸F]FP-CIT, and subsequently returning to clinical application. We investigated the pharmacokinetic properties of [¹⁸F]FP-CIT and its efficacy for PD diagnosis using murine models.

Results: Biodistribution, metabolite and excretion analyses were performed in mice and PD models were induced in rats using 6-hydroxydopamine (6-OHDA). The targeting efficiency of [¹⁸F]FP-CIT for the dopamine receptor was assessed through animal PET/CT imaging. Subsequently, correlation analysis was conducted between animal PET/CT imaging results and immunohistochemistry (IHC) targeting tyrosine hydroxylase. Rapid circulation was confirmed after [¹⁸F]FP-CIT injection. [¹⁸F]FP-CIT reached the highest uptake of 23.50 ± 12.46%ID/g in the striatum 1 min after injection, and it was rapidly excreted within 60 min. The major metabolic organs of [¹⁸F]FP-CIT were confirmed to be the intestines, liver, and kidneys. Its uptake in the intestine was approximately 5% ID/g. The uptake in the liver gradually increased, with excretion beginning after reaching a maximum after 60 min. The kidneys exhibited rapid elimination after 10 min. In the excretion study, rapid elimination was verified, with 21.46 ± 9.53% of the compound excreted within a 6 h period. Additionally, the efficacy of [¹⁸F]FP-CIT PET was demonstrated in the PD model, with a high correlation with IHC for both the absolute value (R = 0.803, p = 0.0017) and the ratio value (R = 0.973, p = 0.0011).

Conclusions: This study fills the gap regarding insufficient preclinical studies on [¹⁸F]FP-CIT, including its ADME, metabolites, and efficiency. The pharmacological results, including accurate diagnosis, rapid circulation, and [¹⁸F]FP-CIT excretion, provide complementary evidence that [¹⁸F]FP-CIT can be used safely and efficiently to diagnose PD in clinics, although it is already used in clinics.

Background: O-(2-[¹⁸F]fluoroethyl)-L-tyrosine positron emission tomography ([¹⁸F]FET PET) scanning is used in routine clinical management and evaluation of gliomas with a recommended 4 h prior fasting. Knowledge of test-retest variation of [¹⁸F]FET PET imaging uptake metrics and the impact of accidental protein intake can be critical for interpretation. The aim of this study was to investigate the repeatability of [¹⁸F]FET-PET metrics and to assess the impact of protein-intake prior to [¹⁸F]FET PET scanning of gliomas.

Results: Test-retest variability in the non-protein group was good with absolute (and relative) upper and lower limits of agreement of + 0.15 and - 0.13 (+ 9.7% and - 9.0%) for mean tumour-to-background ratio (TBR_mean), + 0.43 and - 0.28 (+ 19.6% and - 11.8%) for maximal tumour-to-background ratio (TBR_max), and + 2.14 cm³ and - 1.53 ml (+ 219.8% and - 57.3%) for biological tumour volume (BTV). Variation was lower for uptake ratios than for BTV. Protein intake was associated with a 27% increase in the total sum of plasma concentration of the L-type amino acid transporter 1 (LAT1) relevant amino acids and with decreased standardized uptake value (SUV) in both healthy appearing background brain tissue (mean SUV - 25%) and in tumour (maximal SUV - 14%). Oral intake of 24 g of protein 1 h prior to injection of tracer tended to increase variability, but the effects on derived tumour metrics TBR_mean and TBR_max were only borderline significant, and changes generally within the variability observed in the group with no protein intake.

Conclusion: The test-retest repeatability was found to be good, and better for TBR_max and TBR_mean than BTV, with the methodological limitation that tumour growth may have influenced results. Oral intake of 24 g of protein one hour before a [¹⁸F]FET PET scan decreases uptake of [¹⁸F]FET in both tumour and in healthy appearing brain, with no clinically significant difference on the most commonly used tumour metrics.

Background: Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an urgent need for early diagnosis and accurate staging to facilitate appropriate treatment strategies. In this study, we assessed the diagnostic potential of [¹⁸F]F-FAPI-42 PET/CT imaging for early detection and disease staging in a rat model of PQ-induced lung fibrosis.

Methods: After administering 80 mg/kg of PQ orally to Sprague-Dawley rats, we intravenously injected 3-3.5 MBq of [¹⁸F]F-FAPI-42 on day 7, 14, and 21 post-dosing. Dynamic PET/CT imaging was carried out for one hour immediately after the administration of [¹⁸F]F-FAPI-42. Subsequently, the lung tissues were collected for Hematoxylin and Eosin (HE) staining, Masson's trichrome staining, and NOTA-FAPI-04-MB fluorescent probe staining. Data analysis was performed using the Imalytics preclinical software, and the mean standardized uptake value (SUV_mean) was calculated.

Results: PET signals revealed that in areas with evident lesions on CT, the SUV_mean on day 14 was significantly higher than on day 7 and 21, indicating that changes in fibrosis activity levels contribute to the staging of pulmonary fibrosis. Additionally, the NOTA-FAPI-04-MB fluorescent probe staining also demonstrated the most pronounced probe uptake on day 14. In regions without apparent lesions on CT, the SUV_mean gradually increased from day 7 to day 21, reflecting ongoing fibrotic activity. Moreover, HE staining and Masson's trichrome staining did not reveal pulmonary fibrosis, while PET imaging was able to detect it, serving the purpose of early diagnosis. At 30 min and 60 min, the target-to-background ratio (TBR) of the PQ groups on day 7, 14, and 21 was significantly higher than the control group, suggesting a high specificity of [¹⁸F]F-FAPI-42 binding to activated fibroblasts.

Conclusion: [¹⁸F]F-FAPI-42 PET/CT imaging enables early diagnosis and staging of PQ-induced pulmonary fibrosis, demonstrating its feasibility and potential for characterizing early disease stages.

Background: In preclinical studies, the positron emission tomography (PET) imaging with [¹¹C]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [¹¹C]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding.

Results: Twelve healthy subjects underwent 90-min baseline [¹¹C]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [¹¹C]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [¹¹C]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue.

Conclusions: [¹¹C]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans.