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Introduction SUV measurements from static brain [ 18 F]FDG PET acquisitions are a commonly used tool in preclinical research, providing a simple alternative for kinetic modelling, which requires complex and time-consuming dynamic acquisitions. However, SUV can be severely affected by the animal handling and preconditioning protocols, primarily by those that may induce changes in blood glucose levels (BGL). Here, we aimed at developing and investigating the feasibility of SUV-based approaches for a wide range of BGL far beyond normal values, and consequently, to develop and validate a new model to generate standardized and reproducible SUV measurements for any BGL. Material and methods We performed dynamic and static brain [ 18 F]FDG PET acquisitions in 52 male Sprague-Dawley rats sorted into control (n = 10), non-fasting (n = 14), insulin-induced hypoglycemia (n = 12) and glucagon-induced hyperglycemia (n = 16) groups. Brain [ 18 F]FDG PET images were cropped, aligned and co-registered to a standard template to calculate whole-brain and regional SUV. Cerebral Metabolic Rate of Glucose (CMRglc) was also estimated from 2-Tissue Compartment Model (2TCM) and Patlak plot for validation purposes. Results Our results showed that BGL=100±6 mg/dL can be considered a reproducible reference value for normoglycemia. Furthermore, we successfully established a 2nd-degree polynomial model (C 1 =0.66E-4, C 2 =-0.0408 and C 3 =7.298) relying exclusively on BGL measures at pre-[ 18 F]FDG injection time, that characterizes more precisely the relationship between SUV and BGL for a wide range of BGL values (from 10 to 338 mg/dL). We confirmed the ability of this model to generate corrected SUV estimations that are highly correlated to CMRglc estimations (R 2 = 0.54 2TCM CMRgluc and R 2 = 0.49 Patlak CMRgluc). Besides, slight regional differences in SUV were found in animals from extreme BGL groups, showing that [ 18 F]FDG uptake is mostly directed toward central regions of the brain when BGLs are significantly decreased. Conclusion Our study successfully established a non-linear model that relies exclusively on pre-scan BGL measurements to characterize the relationship between [ 18 F]FDG SUV and BGL. The extensive validation confirmed its ability to generate SUV-based surrogates of CMRglu along a wide range of BGL and it holds the potential to be adopted as a standard protocol by the preclinical neuroimaging community using brain [ 18 F]FDG PET imaging., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The ability of 18 F-FDG positron emission tomography (PET) to track disease activity and treatment response in patients with Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA) remains unclear. Here, we assessed whether 18 F-FDG uptake is a marker of disease activity and treatment response in AS or PsA, and explored the ability of 18 F-FDG to predict treatment response. Patients with AS (n = 16) or PsA (n = 8) who were scheduled to initiate treatment with biologics were recruited. Participants underwent a clinical evaluation and an 18 F-FDG scan prior to therapy initiation. Eleven participants underwent a follow-up 18 F-FDG scan 3 months post-treatment. Images were quantified using a composite measure that describes the inflammatory status of the patient. Clinically involved joints/entheses had higher 18 F-FDG uptake compared to unaffected areas (median difference > 0.6, p < 0.01). Among patients with AS, pre-treatment 18 F-FDG uptake was strongly associated with disease activity (r = 0.65, p = 0.006). Longitudinal 18 F-FDG scans demonstrated that decreases in uptake at 3 months were associated to clinical response (β ΔgSUVmax  > 8.5, p < 0.001). We found no significant association between pre-treatment 18 F-FDG uptake and subsequent clinical response. 18 F-FDG PET shows potential as a marker of disease activity in AS and PsA, allowing for monitorization of biological treatment efficacy in these patients., (© 2024. The Author(s).)

Background: [ 18 F]Flortaucipir (FTP) PET quantification is usually hindered by spill-in counts from off-target binding (OFF) regions. The present work aims to provide an in-depth analysis of the impact of OFF in FTP PET quantification, as well as to identify optimal partial volume correction (PVC) strategies to minimize this problem., Methods: 309 amyloid-beta (Aβ) negative cognitively normal subjects were included in the study. Additionally, 510 realistic FTP images with different levels of OFF were generated using Monte Carlo simulation (MC). Images were corrected for PVC using both a simple two-compartment and a multi-region method including OFF regions. FTP standardized uptake value ratio (SUVR) was quantified in Braak Areas (BA), the hippocampus (which was not included in Braak I/II) and different OFF regions (caudate, putamen, pallidum, thalamus, choroid plexus (ChPlex), cerebellar white matter (cerebWM), hemispheric white matter (hemisWM) and cerebrospinal fluid (CSF)) using the lower portion of the cerebellum as a reference region. The correlations between OFF and cortical SUVRs were studied both in real and in simulated PET images, with and without PVC., Results: In-vivo, we found correlations between all OFF and target regions, especially strong for the hemisWM (slope>0.63, R 2 >0.4). All the correlations were attenuated but remained significant after applying PVC, except for the ChPlex. In MC simulations, the hemisWM and CSF were the main contributors to PVE in all BA (slopes 0.15-0.26 and 0.13-0.21 respectively). The hemisWM (slope=0.2), as well as the ChPlex (slope=0.02), influenced SUVRs in the hippocampus. The CerebWM was negatively correlated with all target regions (slope<-0.02, R 2 >0.8). While no other correlations between OFF and target regions were found, hemisWM was correlated with all OFF regions but the cerebWM (slopes 0.06-0.33). HemisWM correlations attenuated (slopes<0.06) when applying two-compartment PVC, but the hippocampus-ChPlex and the cerebWM correlations required more complex PVC with dedicated compartments for these regions. In-vivo, PVC removed a notably higher fraction of the correlation between OFF regions found to be affected by PVE in the simulation studies and BA (≈50%) than for OFF regions not affected by PVE (16%)., Conclusion: HemisWM is the main driver of spill-in effects in FTP PET, affecting both target regions and the rest of OFF regions. PVC successfully reduces PVE, even when using a simple two-compartment method. Despite PVC, non-zero correlations were still observed between target and OFF regions in vivo, which suggests the existence of biological or tracer-related contributions to these correlations., Competing Interests: Declaration of Competing Interest JSR is an advisor for Qubiotech Health Intelligence SL. PAF is an advisor for Qubiotech Health Intelligence SL., (Copyright © 2022. Published by Elsevier Inc.)

Background and Purpose: Non-invasive imaging methodologies, especially nuclear imaging techniques, have undergone an extraordinary development over the last years. Interest in the development of innovative tracers has prompted the emergence of new nanomaterials with a focus on nuclear imaging and therapeutical applications. Among others, organic nanoparticles are of the highest interest due to their translational potential related to their biocompatibility and biodegradability. Our group has developed a promising new type of biocompatible nanomaterials, sphingomyelin nanoemulsions (SNs). The aim of this study is to explore the potential of SNs for nuclear imaging applications., Methods: Ready-to-label SNs were prepared by a one-step method using lipid derivative chelators and characterized in terms of their physicochemical properties. Stability was assessed under storage and after incubation with human serum. Chelator-functionalized SNs were radiolabeled with 67 Ga and 68 Ga, and the radiochemical yield (RCY), radiochemical purity (RCP) and radiochemical stability (RCS) were determined. Finally, the biodistribution of 67/68 Ga-SNs was evaluated in vivo and ex vivo., Results: Here, we describe a simple and mild one-step method for fast and efficient radiolabeling of SNs with 68 Ga and 67 Ga radioisotopes. In vivo experiments showed that 67/68 Ga-SNs can efficiently and indistinctly be followed up by PET and SPECT. Additionally, we proved that the biodistribution of the 67/68 Ga-SNs can be conveniently modulated by modifying the surface properties of different hydrophilic polymers, and therefore the formulation can be further adapted to the specific requirements of different biomedical applications., Conclusion: This work supports 67/68 Ga-SNs as a novel probe for nuclear imaging with tunable biodistribution and with great potential for the future development of nanotheranostics., Competing Interests: The author reports no conflicts of interest in this work., (© 2021 Díez-Villares et al.)

Purpose: Preclinical dynamic brain PET studies remain hampered by the limitations related to the measurement of the arterial input function (AIF). In this regard, the use of an arterial-venous shunt is a promising method for the generation of real-time AIFs, but its application in longitudinal studies is still impeded by the cumbersome surgeries and high failure rates. We studied the feasibility and reproducibility of double arterial-venous shunt strategies for conducting longitudinal PET studies with real-time AIFs in rats., Procedures: We studied the feasibility of double arterial-venous shunts in rats in the right/left inguinal region and evaluated inter-animal and intra-animal AIF reproducibilities. Image-derived input function (IDIF) was also obtained for comparison. Dynamic brain FDG PET studies were conducted to estimate kinetic constants and Cerebral Metabolic Rate of Glucose (CMR glc ) obtained from standard 2-tissue compartment (2TCM) and Patlak analysis., Results: We showed that longitudinal AIFs from double arterial-venous shunts can be obtained with very high success rate of the surgeries (88 %). Our results provided highly reproducible AIF measurements with low inter-animal variabilities (11 %) and intra-animal variabilities (5-10 %) that were included into the kinetic models, such that longitudinal rate constants and CMR glc can be efficiently estimated without bias associated to the double shunt. Our results indicated that longitudinal IDIF can be also generated without bias along time but showing higher intra-animal uncertainties., Conclusions: We have demonstrated the feasibility and high reproducibility of conducting longitudinal AIF measurements and consequently accurate kinetic modeling using arterial shunt method.

Intravitreal injections are the standard procedure in the treatment of retinal pathologies, such as the administration of the anti-VEGF antibodies in age-related macular degeneration. The aim of this study is to evaluate the intraocular and blood pharmacokinetics after an intravitreal injection of 89 Zr-labelled bevacizumab and 89 Zr-labelled aflibercept in Sprague-Dawley rats using Positron Emission Tomography. First, both antibodies were radiolabelled to zirconium-89 with a maximum specific activity of 15 Mbq/mg for bevacizumab and 10 Mbq/mg for aflibercept. Four µL containing 1-1.2 Mq of 89 Zr-labelled compound were injected into the vitreous through a 35 G needle. A microPET acquisition was carried out immediately after the injection and at different time points through a 12-day study and blood samples were obtained through the tail vein. Radiolabelling was successfully performed with a radiochemical purity after ultrafiltration above 95% for both agents. Both antibodies ocular curves followed a two-compartment model in which an intraocular elimination half-life of 16.44 h was found for 89 Zr-bevacizumab and 4.51 h for 89 Zr-aflibercept, considering the alpha phase as the elimination phase. Regarding the beta phase, a half-life of 3.23 days for 89 Zr-bevacizumab and 4.69 days for 89 Zr-aflibercept were observed. With regards to blood concentration, 89 Zr-bevacizumab showed a blood half-life of 7.08 days, whereas 89 Zr-aflibercept's was 3.18 days, by a one-compartment model with first-order absorption kinetics. In conclusion, this study shows for the first time the ocular and blood pharmacokinetic analysis after intravitreal injection of aflibercept and bevacizumab in rats., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the diagnostic value of dedicated breast PET (dbPET) parallel imaging in mammographically or sonographically detected BI-RADS 4 (Breast Imaging Reporting And Data Systems) lesions., Materials and Methods: After institutional review board and patient approvals, 50 consecutive women with 60 BI-RADS 4 breast lesions were prospectively included in the study. All patients underwent Magnetic Resonance Imaging (MRI) and dbPET before biopsy and fusion of both MRI and dbPET images was performed to better locate corresponding lesions. Final findings were compared with histological results. Sensitivity and specificity for dbPET were determined along with their respective 95%-confidence intervals., Results: Histopathology examination revealed 18 malignant lesions (7 in situ and 11 invasive carcinomas) and 42 benign entities. The dedicated breast PET reported no evidence of malignancy in 41 patients, 9 of them with histological diagnosis of neoplasm. Besides, dbPET showed increased metabolically activity in 10 benign lesions and in 9 breast cancers. Two invasive carcinomas were located less than 1 cm from the pectoral muscle, which can explain that they were missed by dbPET because they were outside the field of view (FOV). There were other 6 false negative results, which corresponded to a 0.1 cm invasive lobular carcinoma and 5 in situ carcinomas. Sensitivity and specificity of dbPET were 50% and 76%, respectively., Conclusions: Our analysis does not allow the recommendation of dbPET for diagnosis of malignancy in BI-RADS 4 mammographic or US abnormalities, mainly due to its high false-negative rate for the detection of in situ carcinomas (85.7%). However, considering the lesions greater than 0.1 cm and included in the FOV, dbPET depicted all invasive carcinomas., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: This study aims to determine whether PET textural features measured with a new dedicated breast PET scanner reflect biological characteristics of breast tumors., Methods: One hundred and thirty-nine breast tumors from 127 consecutive patients were included in this analysis. All of them underwent a 18 F-FDG PET scan before treatment. Well-known PET quantitative parameters such as SUV m a x , SUV m e a n , metabolically active tumor volume (MATV) and total lesion glycolysis (TLG) were extracted. Together with these parameters, local, regional, and global heterogeneity descriptors, which included five textural features (TF), were computed. Immunohistochemical classification of breast cancer considered five subtypes: luminal A like (LA), luminal B like/HER2 - (LB -), luminal B like/HER2+ (LB+), HER2-positive-non-luminal (HER2pnl), and triple negative (TN). Associations between PET features and tumor characteristics were assessed using non-parametric hypothesis tests., Results: Along with well-established associations, new correlations were found. HER2-positive tumors had significantly higher uptake (p < 0.001, AUCs > 0.70) and presented different global and regional heterogeneity (p = 0.002, p = 0.016, respectively, AUCs < 0.70). Nine out of ten analyzed features were significantly associated with immunohistochemical subtype. Uptake was lower for LA tumors (p < 0.001) with AUCs ranging from 0.71 to 0.88 for each subgroup comparison. Heterogeneity metrics were significantly associated when comparing LA and LB - (p < 0.01), being regional heterogeneity metrics more discriminative than any other parameter (AUC = 0.80 compared to AUC = 0.71 for SUV). LB+ and HER2pnl tumors also showed more regional heterogeneity than LA tumors (AUCs = 0.79 and 0.84, respectively). After comparison with whole-body PET studies, we observed an overall improvement in the classification ability of both non-heterogeneity metrics and textural features., Conclusions: PET parameters extracted from high-resolution dedicated breast PET images showed new and stronger correlations with immunohistochemical factors and immunohistochemical subtype of breast cancer compared to whole-body PET.

The spill-in counts from neighbouring regions can significantly bias the quantification over small regions close to high activity extended sources. This effect can be a drawback for (18)F-based radiotracers positron emission tomography (PET) when quantitatively evaluating the bladder area for diseases such as prostate cancer. In this work, we use Monte Carlo simulations to investigate the impact of the spill-in counts from the bladder on the quantitative evaluation of prostate cancer when using (18)F-Fluorcholine (FCH) PET and we propose a novel reconstruction-based correction method. Monte Carlo simulations of a modified version of the XCAT2 anthropomorphic phantom with (18)F-FCH biological distribution, variable bladder uptake and inserted prostatic tumours were used in order to obtain simulated realistic (18)F-FCH data. We evaluated possible variations of the measured tumour Standardized Uptake Value (SUV) for different values of bladder uptake and propose a novel correction by appropriately adapting image reconstruction methodology. The correction is based on the introduction of physiological background terms on the reconstruction, removing the contribution of the bladder to the final image. The bladder is segmented from the reconstructed image and then forward-projected to the sinogram space. The resulting sinograms are used as background terms for the reconstruction. SUV max and SUV mean could be overestimated by 41% and 22% respectively due to the accumulation of radiotracer in the bladder, with strong dependence on bladder-to-lesion ratio. While the SUVs measured under these conditions are not reliable, images corrected using the proposed methodology provide better repeatability of SUVs, with biases below 6%. Results also showed remarkable improvements on visual detectability. The spill-in counts from the bladder can affect prostatic SUV measurements of (18)F-FCH images, which can be corrected to less than 6% using the proposed methodology, providing reliable SUV values even in the presence of high radioactivity accumulation in the bladder.