Accurate Total-Body Ki Parametric Imaging with Shortened Dynamic 18F-FDG PET Scan Durations via Effective Data Processing

Background: Total-body dynamic PET (dPET) imaging using 18F-fluorodeoxyglucose (18F-FDG) has received widespread attention in clinical oncology. However, the conventionally required scan duration of approximately one hour seriously limits the application and promotion of this imaging technique. In this study, using Patlak analysis-based Ki parametric imaging as the evaluation standard, we investigated the possibility and feasibility of shortening the total-body dynamic scan duration to 30 mins post-injection (PI) with the help of a novel Patlak data processing algorithm.Methods: Total-body dPET images acquired by uEXPLORER (United Imaging Healthcare Inc.) using 18F-FDG of 15 patients with different types of tumors were analyzed in this study. Dynamic images were reconstructed into 25 frames with a specific temporal dividing protocol for the scan data acquired one hour PI. Patlak analysis-based Ki parametric imaging was carried out based on the imaging data corresponding to the first 30 mins PI, during which a Patlak data processing method based on third-order Hermite interpolation (THI) was applied. The resulting Ki images and standard Ki images were compared in terms of visual imaging effect and Ki estimation accuracy to evaluate the performance of the proposed data processing algorithm for parametric imaging with dPET with a shortened scan duration.Results: With the help of Patlak data processing, acceptable Ki parametric images were obtained from dPET data acquired with a shortened scan duration. Compared to Ki images obtained from unprocessed Patlak data, the resulting images from the proposed method contained less image noise, leading to remarkably improved imaging quality. Moreover, box plot analysis showed that that 30-min Ki images obtained from processed Patlak data have higher accuracy regarding tumor lesion Ki values.Conclusion: Acceptable Ki parametric images can be acquired from dynamic imaging data corresponding to the first 30 mins PI. Patlak data processing can help achieve higher Ki imaging quality and higher accuracy regarding tumor lesion Ki values. Clinically, it is possible to shorten the dynamic scan duration of 18F-FDG PET to 30 mins to facilitate the usage of such imaging techniques on uEXPLORER scanners.

68Ga-P15-041, A Novel Bone Imaging Agent for Diagnosis of Bone Metastases

Objectives68Ga-P15-041 (68Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer, which can be readily prepared by using a simple kit formulation and an in-house 68Ga/68Ge generator. The aim of this study is to assess the potential human application of 68Ga-P15-041 for clinical PET/CT imaging and to compare its efficacy to detect bone metastases of different cancers with 99mTc-MDP whole-body bone scintigraphy (WBBS).MethodsInitial kinetic study using Patlak analysis and parametric maps were performed in five histopathologically proven cancer patients (three males, two females) using 68Ga-P15-041 PET/CT scan only. Another group of 51 histopathologically proven cancer patients (22 males, 29 females) underwent both 99mTc-MDP WBBS and 68Ga-P15-041 PET/CT scans within a week, sequentially. Using either pathology examination or follow-up CT or MRI scans as the gold standard, the diagnostic efficacy and receiver operating characteristic curve (ROC) of the two methods in identifying bone metastases were compared (p <0.05, statistically significant).ResultsFifty-one patients were imaged, and 174 bone metastatic sites were identified. 68Ga-P15-041 PET/CT and 99mTc-MDP WBBS detected 162 and 81 metastases, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 68Ga-P15-041 PET/CT and 99mTc-MDP WBBS were 93.1% vs 81.8%, 89.8% vs 90.7%, 77.5% vs 69.2%, 97.2% vs 93.4% and 90.7% vs 88.4%, respectively. Our results showed that the mean of SUVmax was significantly higher in metastases than that in benign lesions, 15.1 ± 6.9 vs. 5.6 ± 1.3 (P <0.001). Using SUVmax = 7.6 as the cut-off value by PET/CT, it was possible to predict the occurrence of metastases (AUC = 0.976; P <0.001; 95% CI: 0.946–0.999). However, it was impossible to distinguish osteoblastic bone metastases from osteolytic bone lesions. Parametric maps based on Patlak analysis provided excellent images and highly valuable quantitative information.Conclusions68Ga-P15-041 PET/CT, offering a rapid bone scan and high contrast images in minutes, is superior to the current method of choice in detecting bone metastases. It is reasonable to suggest that 68Ga-P15-041 PET/CT could become a valuable routine nuclear medicine procedure in providing excellent images for detecting bone metastases in cancer patients. 68Ga-P15-041 could become a valuable addition expanding the collection of 68Ga-based routine nuclear medicine procedures where 18F fluoride is not currently available.

Comparison of [18F] NaF PET/CT dynamic analysis methods and a static analysis method including derivation of a semi-population input function for site-specific measurements of bone formation in a population with chronic kidney disease-mineral and bone disorder

Purpose The purpose of this study is to compare dynamic and static whole-body (WB) [18F]NaF PET/CT scan methods used for analysis of bone plasma clearance in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). Methods Seventeen patients with CKD-MBD underwent a 60-min dynamic scan followed by a 30-min static WB scan. Tracer kinetics in four thoracic vertebrae were analysed using nonlinear regression and Patlak analysis using image-derived arterial input functions. The static WB scan was analysed using a simplified Patlak method requiring only a single data point in combination with a fixed y-intercept value (V0), both obtained using a semi-population function. The semi-population function was constructed by combining a previously derived population input function in combination with data from venous blood samples. Static WB scan analysis data, obtained from the semi-population input functions, was compared with paired data obtained using dynamic input functions. Results Bone plasma clearance (Ki) from Patlak analyses correlated well with nonlinear regression analysis, but Ki results using Patlak analysis were lower than Ki results using nonlinear regression analysis. However, no significant difference was found between Ki obtained by static WB scans and Ki obtained by dynamic scans using nonlinear regression analysis (p = 0.29). Conclusion Bone plasma clearance measured from static WB scans correlates with clearance data measured by dynamic analysis. Static [18F]NaF PET/CT scans can be applied in future studies to measure Ki in patients with CKD-MBD, but the results should not be compared uncritically with results obtained by dynamic scan analysis.

Comparison of [18F] NaF PET/CT Analysis Methods and Derivation of a Semi-population Input Function for Site Specific Measurements of Bone Formation in a Population With Chronic Kidney Disease Mineral and Bone Disorder

PurposeImplementation and comparison of non-invasive dynamic and static whole-body (WB) [18F]NaF PET/CT scan methods to replace invasive bone biopsy, used for quantitative analysis of bone clearance in patients with chronic kidney disease - mineral and bone disorder (CKD-MBD).MethodsSeventeen patients with CKD-MBD underwent a 60-minute dynamic scan followed by a 30-minute static WB scan. Tracer kinetics in four thoracic vertebrae were analyzed using non-linear regression and Patlak analysis using image-derived arterial input functions. We validated the use of a semi-population input function in this population.ResultsSkeletal plasma clearance (Ki) from Patlak analyses correlated well with non-linear regression analysis, but Ki-results using Patlak analysis were lower compared to Ki-results using non-linear regression analysis. However, no significant difference was found between Ki obtained by static WB scans and Ki obtained by dynamic scans using non-linear regression analysis (p=0.29). ConclusionOur results show good correlation between dynamic and static analysis of skeletal plasma clearance with no significant difference between the Ki-results obtained by non-linear regression analysis and the more clinically suitable static scan analysis method. We found lower Ki-results when Patlak analysis was applied. Thus, WB [18F]NaF PET/CT scans can be applied in future studies to measure Ki in CKD-BMD patients, but the results should not be compared uncritically with results obtained by dynamic scans analysis.

Use of population input functions for reduced scan duration whole-body Patlak 18F-FDG PET imaging

Whole-body Patlak images can be obtained from an acquisition of first 6 min of dynamic imaging over the heart to obtain the arterial input function (IF), followed by multiple whole-body sweeps up to 60 min pi. The use of a population-averaged IF (PIF) could exclude the first dynamic scan and minimize whole-body sweeps to 30–60 min pi. Here, the effects of (incorrect) PIFs on the accuracy of the proposed Patlak method were assessed. In addition, the extent of mitigating these biases through rescaling of the PIF to image-derived IF values at 30–60 min pi was evaluated. Methods Using a representative IF and rate constants from the literature, various tumour time-activity curves (TACs) were simulated. Variations included multiplication of the IF with a positive and negative gradual linear bias over 60 min of 5, 10, 15, 20, and 25% (generating TACs using an IF different from the PIF); use of rate constants (K1, k3, and both K1 and k2) multiplied by 2, 1.5, and 0.75; and addition of noise (μ = 0 and σ = 5, 10 and 15%). Subsequent Patlak analysis using the original IF (representing the PIF) was used to obtain the influx constant (Ki) for the differently simulated TACs. Next, the PIF was scaled towards the (simulated) IF value using the 30–60-min pi time interval, simulating scaling of the PIF to image-derived values. Influence of variabilities in IF and rate constants, and rescaling the PIF on bias in Ki was evaluated. Results Percentage bias in Ki observed using simulated modified IFs varied from − 16 to 16% depending on the simulated amplitude and direction of the IF modifications. Subsequent scaling of the PIF reduced these Ki biases in most cases (287 out of 290) to < 5%. Conclusions Simulations suggest that scaling of a (possibly incorrect) PIF to IF values seen in whole-body dynamic imaging from 30 to 60 min pi can provide accurate Ki estimates. Consequently, dynamic Patlak imaging protocols may be performed for 30–60 min pi making whole-body Patlak imaging clinically feasible.

Validation and Comparison of [18F]NaF PET/CT Analysis Methods and Derivation of a Semi-population Input Function for Site Specific Measurements of Bone Formation in a Population with Chronic Kidney Disease Mineral and Bone Disorder

BackgroundMethods for assessing bone metabolism which can replace the gold standard bone biopsy are sorely needed in the clinical setting in patients with chronic kidney disease - mineral and bone disorder (CKD-MBD). The aim of the present study was implementation, validation and comparison of non-invasive dynamic and static whole-body (WB) [18F]NaF PET/CT scan methods to replace invasive bone biopsy, used for quantitative analysis of bone clearance in CKD-MBD patients.MethodsSeventeen patients with CKD-MBD underwent a 60-minute dynamic scan followed by a 30-minute static WB scan. Tracer kinetics in four thoracic vertebrae were analyzed using non-linear regression with the Hawkins model and two different Patlak-analysis methods using image-derived arterial input functions obtained from the left myocardial ventricle and the thoracic aorta. For future use in WB PET/CT scans, we validated the use of a semi-population input function. The resulting kinetic parameters (Ki, K1, k2, k3, k4, V0) were compared between the different methods of analysis using the various derived input functions.ResultsDynamic kinetic results from both standard and single-point Patlak analyses correlate well with non-linear regression analysis, but Ki results using Patlak analysis are generally lower for all tested input functions compared to regression analysis. Single-point Patlak analysis on WB scans correlates well with standard Patlak analysis on dynamic scans but show 13-21% higher Ki-values. ConclusionsOur results show good correlation between dynamic and static analysis of skeletal plasma clearance but different Ki-values depending on the analysis method and choice of input function used. Thus, WB [18F]NaF PET/CT scans can be applied in future studies, but the results should not be compared uncritically with results obtained using non-linear regression analysis.

Influence of O-Methylated Metabolite Penetrating the Blood–Brain Barrier to Estimation of Dopamine Synthesis Capacity in Human L-[β-11C]DOPA PET

O-methyl metabolite (L-[ β-11C]OMD) of 11C-labeled L-3,4-dihydroxyphenylalanine (L-[ β-11C]DOPA) can penetrate into brain tissue through the blood–brain barrier, and can complicate the estimation of dopamine synthesis capacity by positron emission tomography (PET) study with L-[ β-11C]DOPA. We evaluated the impact of L-[ β-11C]OMD on the estimation of the dopamine synthesis capacity in a human L-[ β-11C]DOPA PET study. The metabolite correction with mathematical modeling of L-[ β-11C]OMD kinetics in a reference region without decarboxylation and further metabolism, proposed by a previous [18F]FDOPA PET study, were implemented to estimate radioactivity of tissue L-[ β-11C]OMD in 10 normal volunteers. The component of L-[ β-11C]OMD in tissue time-activity curves (TACs) in 10 regions were subtracted by the estimated radioactivity of L-[ β-11C]OMD. To evaluate the influence of omitting blood sampling and metabolite correction, relative dopamine synthesis rate ( kref) was estimated by Gjedde–Patlak analysis with reference tissue input function, as well as the net dopamine synthesis rate ( Ki) by Gjedde–Patlak analysis with the arterial input function and TAC without and with metabolite correction. Overestimation of Ki was observed without metabolite correction. However, the kref and Ki with metabolite correction were significantly correlated. These data suggest that the influence of L-[ β-11C]OMD is minimal for the estimation of kref as dopamine synthesis capacity.

[11C]5-HTP and microPET are Not Suitable for Pharmacodynamic Studies in the Rodent Brain

The PET tracer [11C]5-hydroxytryptophan ([11C]5-HTP), which is converted to [11C]5-hydroxytryptamine ([11C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [11C]5-HTP in rat? Male rats were scanned with [11C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [11C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [11C]5-HTP uptake, and the k3. This was unexpected as NSD 1015 directly inhibits the enzyme converting [11C]5-HTP to [11C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [11C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.