Radiotracer Concentration Research Articles

Evaluating the Effect of Extra-Cerebral Off-Target Binding in [F-18]MK6240 PET Scans in Early-Stage Alzheimer’s Disease

Abstract [F-18]MK6240 is a PET radioligand with favorable imaging characteristics for measuring tau aggregation in Alzheimer’s disease (AD). In this study we investigated the impact of extra-cerebral off-target binding (ECB) in the meninges and sinus present in [F-18]MK6240 PET scans on quantifying tau burden in preclinical AD. Based on large cohort data from 433 [F-18]MK6240 scans acquired at the University of Wisconsin-Madison, simulations were conducted to examine the range of effects of ECB by varying the ECB profile and input radiotracer concentration curves on areas of early tau accumulation in AD. The range and patterning of ECB in the imaging cohort had high variability between participants, however, 35% revealed moderate to high meningeal signal that could influence quantification. Partial volume effects, which can lead to measured PET signal from neighboring regions influencing signal in adjacent areas of interest, were examined in the simulated images. The simulations demonstrate that signal from the sinus increases the neighboring entorhinal cortex region (ERC) signal and activity detected from the meninges can similarly influence the inferior cerebellar grey matter reference region. ECB effects from the sinus were most prevalent in our cohort, and simulations with the average ECB profile had ERC uptake (SUV) 23% higher than simulations with no ECB. Spill-in effects from the sinus, which increases the medial and ventral temporal cortex SUVR, and spill-in from the meninges into the cerebellar reference region, which leads to a reduction in global SUVR, act in opposite directions, complicating the interpretation of the derived SUVR of [F-18]MK6240 images. These simulation results quantify the effects of ECB in [F-18]MK6240 scans and introduce correction factors to minimize bias of the SUVR measure.

Feasibility study of a SiPM-fiber detector for non-invasive measurement of arterial input function for preclinical and clinical positron emission tomography

Pharmacokinetic positron emission tomography (PET) studies rely on the measurement of the arterial input function (AIF), which represents the time-activity curve of the radiotracer concentration in the blood plasma. Traditionally, obtaining the AIF requires invasive procedures, such as arterial catheterization, which can be challenging, time-consuming, and associated with potential risks. Therefore, the development of non-invasive techniques for AIF measurement is highly desirable. This study presents a detector for the non-invasive measurement of the AIF in PET studies. The detector is based on the combination of scintillation fibers and silicon photomultipliers (SiPMs) which leads to a very compact and rugged device. The feasibility of the detector was assessed through Monte Carlo simulations conducted on mouse tail and human wrist anatomies studying relevant parameters such as energy spectrum, detector efficiency and minimum detectable activity (MDA). The simulations involved the use of 18F and 68Ga isotopes, which exhibit significantly different positron ranges. In addition, several prototypes were built in order to study the different components of the detector including the scintillation fiber, the coating of the fiber, the SiPMs, and the operating configuration. Finally, the simulations were compared with experimental measurements conducted using a tube filled with both 18F and 68Ga to validate the obtained results. The MDA achieved for both anatomies (approximately 1000 kBq/mL for mice and 1 kBq/mL for humans) falls below the peak radiotracer concentrations typically found in PET studies, affirming the feasibility of conducting non-invasive AIF measurements with the fiber detector. The sensitivity for measurements with a tube filled with 18F (68Ga) was 1.2 (2.07) cps/(kBq/mL), while for simulations, it was 2.81 (6.23) cps/(kBq/mL). Further studies are needed to validate these results in pharmacokinetic PET studies.

In Vivo Evaluation of Brain [18F]F-FDG Uptake Pattern Under Different Anaesthesia Protocols.

Since the use of anaesthetics has the drawback of altering radiotracer distribution, preclinical positron emission tomography (PET) imaging findings of anaesthetised animals must be carefully handled. This study aimed at assessing the cerebral [18F]F-FDG uptake pattern in healthy Wistar rats under four different anaesthesia protocols using microPET/magnetic resonance imaging (MRI) examinations. Post-injection of 15±1.2 MBq of [18F]F-FDG, either while awake or during the isoflurane-induced incubation phase was applied. Prior to microPET/MRI imaging, one group of the rats was subjected to forane-only anaesthesia while the other group was anaesthetised with the co-administration of forane and dexmedetomidine/Dexdor® Results: While as for the whole brain it was the addition of dexmedetomidine/Dexdor® to the anaesthesia protocol that generated the differences between the radiotracer concentrations of the investigated groups, regarding the cortex, the [18F]F-FDG accumulation was rather affected by the way of incubation. To ensure the most consistent and highest uptake, forane-induced anaesthesia coupled with an awake uptake condition seemed to be most suitable method of anaesthetisation for cerebral metabolic assessment. Diminished whole brain and cortical tracer accumulation detected upon dexmedetomidine/Dexdor® administration highlights the significance of the mechanism of action of different anaesthetics on radiotracer pharmacokinetics. Overall, the standardization of PET protocols is of utmost importance to avoid the confounding factors derived from anaesthesia.

Parametric and non-parametric Poisson regression for modelling of the arterial input function in positron emission tomography

Full quantification of Positron Emission Tomography (PET) requires an arterial input function (AIF) for measurement of certain targets, or using particular radiotracers, or for the quantification of specific outcome measures. The AIF represents the measurement of radiotracer concentrations in the arterial blood plasma over the course of the PET examination. Measurement of the AIF is prone to error as it is a composite measure created from the combination of multiple measurements of different samples with different equipment, each of which can be sources of measurement error. Moreover, its measurement requires a high degree of temporal granularity for early time points, which necessitates a compromise between quality and quantity of recorded samples. For these reasons, it is often desirable to fit models to this data in order to improve its quality before using it for quantification of radiotracer binding in the tissue. The raw observations of radioactivity in arterial blood and plasma samples are derived from radioactive decay, which is measured as a number of recorded counts. Count data have several specific properties, including the fact that they cannot be negative as well as a particular mean-variance relationship. Poisson regression is the most principled modelling strategy for working with count data, as it both incorporates and exploits these properties. However, no previous studies to our knowledge have taken this approach, despite the advantages of greater efficiency and accuracy which result from using the appropriate distributional assumptions. Here, we implement a Poisson regression modelling approach for the AIF as proof-of-concept of its application. We applied both parametric and non-parametric models for the input function curve. We show that a negative binomial distribution is a more appropriate error distribution for handling overdispersion. Furthermore, we extend this approach to a hierarchical non-parametric model which is shown to be highly resilient to missing data. We thus demonstrate that Poisson regression is both feasible and effective when applied to AIF data, and propose that this is a promising strategy for modelling blood count data for PET in future.

Impact of forced diuresis at two different time points on pelvic imaging in prostatic carcinoma with 68Ga-PSMA PET/CT.

We compared diagnostic quality of 68Ga-PSMA PET/CT imaging focused on the pelvic structures using two furosemide protocols in two different groups of patients. A total of 55 patients with prostate cancer were retrospectively enrolled in the study. Out of 55, 31 patients were in group 1 (median age: 66 years, Range 44-78 years) in which furosemide injection was given after completion of whole-body 68Ga-PSMA PET/CT scan and 24 patients were in group 2 (median age: 63.5 years, range: 50-82 years) in which it was given along with the 68Ga-PSMA injection. In both groups, an initial time point scan (T0 scan) and a delayed time point scan (T1scan) were done. The images were analyzed qualitatively as well as quantitatively. Quantitatively there was no statistically significant difference between the SUVmax and T:B of prostatic lesion and seminal vesicle invasion (SVI) in both the groups at two time points (P > 0.05). Early furosemide injection caused a washout of the urinary bladder radiotracer concentration in significantly higher number of patients in group 2 (62.5% vs. 6.45% patients, P < 0.001). There was significant clearance of radiotracer activity from the ureters in group 2 (SUVmax: 9.28 vs. 3.09, P = 0.002). The simultaneous furosemide and 68Ga-PSMA injection can reduce the urinary excretion of the tracer and improve the diagnostic confidence of prostatic lesion, SVI and lymph nodal metastasis, along with reducing the scanning time and radiation burden, making this protocol an effective alternative to the present protocol of delayed furosemide injection.

Dispersion-corrected extracorporeal arterial input functions in PET studies of mice: a comparison to intracorporeal microprobe measurements

BackgroundKinetic modelling of dynamic PET typically requires knowledge of the arterial radiotracer concentration (arterial input function, AIF). Its accurate determination is very difficult in mice. AIF measurements in an extracorporeal shunt can be performed; however, this introduces catheter dispersion. We propose a framework for extracorporeal dispersion correction and validated it by comparison to invasively determined intracorporeal AIFs using implanted microprobes.ResultsThe response of an extracorporeal radiation detector to radioactivity boxcar functions, characterised by a convolution-based dispersion model, gave best fits using double-gamma variate and single-gamma variate kernels compared to mono-exponential kernels for the investigated range of flow rates. Parametric deconvolution with the optimal kernels was performed on 9 mice that were injected with a bolus of 39 ± 25 MBq [18F]F-PSMA-1007 after application of an extracorporeal circulation for three different flow rates in order to correct for dispersion. Comparison with synchronous implantation of microprobes for invasive aortic AIF recordings showed favourable correspondence, with no significant difference in terms of area-under-curve after 300 s and 5000 s. One-tissue and two-tissue compartment model simulations were performed to investigate differences in kinetic parameters between intra- and extracorporeally measured AIFs. Results of the modelling study revealed kinetic parameters close to the chosen simulated values in all compartment models.ConclusionThe high correspondence of simultaneously intra- and extracorporeally determined AIFs and resulting model parameters establishes a feasible framework for extracorporeal dispersion correction. This should allow more precise and accurate kinetic modelling in small animal experiments.

18F]DPA-714: Effect of co-medications, age, sex, BMI and TSPO polymorphism on the human plasma input function.

We aimed to assess the effect of concomitant medication, age, sex, body mass index and 18-kDa translocator protein (TSPO) binding affinity status on the metabolism and plasma pharmacokinetics of [18F]DPA-714 and their influence on the plasma input function in a large cohort of 201 subjects who underwent brain and whole-body PET imaging to investigate the role of neuroinflammation in neurological diseases. The non-metabolized fraction of [18F]DPA-714 was estimated in venous plasma of 138 patients and 63 healthy controls (HCs; including additional arterial sampling in 16 subjects) during the 90min brain PET acquisition using a direct solid-phase extraction method. The mean fraction between 70 and 90min post-injection ([18F]DPA-71470-90) and corresponding normalized plasma concentration (SUV70-90) were correlated with all factors using a multiple linear regression model. Differences between groups (arterial vs venous measurements; HCs vs patients; high- (HAB), mixed- (MAB) and low-affinity binders (LAB); subjects with vs without co-medications, females vs males were also assessed using the non-parametric Mann-Whitney or Kruskal-Wallis ANOVA tests. Finally, the impact of co-medications on the brain uptake of [18F]DPA-714 at equilibrium was investigated. As no significant differences were observed between arterial and venous [18F]DPA-71470-90 and SUV70-90, venous plasma was used for correlations. [18F]DPA-71470-90 was not significantly different between patients and HCS (59.7 ± 12.3% vs 60.2 ± 12.9%) despite high interindividual variability. However, 47 subjects exhibiting a huge increase or decrease of [18F]DPA-71470-90 (up to 88% or down to 23%) and SUV70-90 values (2-threefold) were found to receive co-medications identified as inhibitors or inducers of CYP3A4, known to catalyse [18F]DPA-714 metabolism. Comparison between cortex-to-plasma ratios using individual input function (VTIND) or population-based input function derived from untreated HCs (VTPBIF) indicated that non-considering the individual metabolism rate led to a bias of about 30% in VT values. Multiple linear regression model analysis of subjects free of these co-medications suggested significant correlations between [18F]DPA-71470-90 and age, BMI and sex while TSPO polymorphism did not influence the metabolism of the radiotracer. [18F]DPA-714 metabolism fell with age and BMI and was significantly faster in females than in males. Whole-body PET/CT exhibited a high uptake of the tracer in TSPO-rich organs (heart wall, spleen, kidneys…) and those involved in metabolism and excretion pathways (liver, gallbladder) in HAB and MAB with a strong decrease in LAB (-89% and -85%) resulting in tracer accumulation in plasma (4.5 and 3.3-fold increase). Any co-medication that inhibits or induces CYP3A4 as well as TSPO genetic status, age, BMI and sex mostly contribute to interindividual variations of the radiotracer metabolism and/or concentration that may affect the input function of [18F]DPA-714 and consequently its human brain and peripheral uptake. INFLAPARK, NCT02319382, registered December 18, 2014, retrospectively registered; IMABIO 3, NCT01775696, registered January 25, 2013, retrospectively registered; INFLASEP, NCT02305264, registered December 2, 2014, retrospectively registered; EPI-TEP, EudraCT 2017-003381-27, registered September 24, 2018.

Cervical catheter placement leads to improved rostral distribution of a radiolabeled 18F-baclofen analog in cynomolgus monkeys

BackgroundIntrathecal (IT) catheter delivery of baclofen via continuous infusion using an implantable pump is an important means of treating patients with severe spasticity. We evaluated the impact of IT catheter tip placement (upper vs. lower) on brain and spine distribution of a radioactive tracer molecule.MethodsCynomolgus monkeys were implanted with an IT catheter, with the distal tip located at either C1 or T10 and attached to an implanted continuous infusion pump. A radioactive tracer molecule, an 18F-baclofen analog, and PET imaging were utilized to observe tracer distribution and quantitate levels of tracer in both the brain and spine according to catheter tip location.ResultsIt was consistently determined that a high cervical (C1) catheter tip placement resulted in both more rapid distribution and higher concentrations of radiotracer in the brain and upper spine compared with lower thoracic (T10) during the first 6 hours of infusion.ConclusionsThese results indicate that delivery of 18F-baclofen by IT catheter results in repeatable proportional distribution within regions of the brain and spine. The data also suggest that the greatest exposure to the brain and cervical spinal cord occurs when the catheter tip is located at the first cervical vertebra.

Papillary Thyroid Carcinoma Arising in Thyroglossal Duct Cyst and Locally Infiltrated to Hyoid Bone: Issue of Individualized Management

Thyroglossal duct cyst (TGDC) is the most common developmental anomaly of the thyroid gland, while TGDC carcinoma with local infiltration to the hyoid bone is extremely rare. The reported case of papillary thyroid carcinoma (PTC) was diagnosed in TGDC along with local infiltration to the hyoid bone and needed individualized management. A 70-year-old male patient presented with a history of PTC arising in TGDC and locally infiltrated to the hyoid bone followed by total thyroidectomy and radical sistrunk operations and was referred to National Institute of Nuclear Medicine and Allied Sciences (NINMAS) for radioactive iodine therapy (RAIT). His post-operative ultrasound of the neck revealed an irregular shaped, fungating, grossly non-homogenous mixed echogenic mass lesion invading the hyoid bone, measuring about 25 X 28 mm. Radioactive iodine(131I) of 150 mCi was administered because the residual hyoid bone mass was inoperable and he was on thyroxine suppression therapy. The post-therapy 131I scan (RxWBS) showed two intense foci of radiotracer concentration (RTC) in the upper area (above the thyroid bed) and an intense focal RTC in the fundal region of the stomach. The activity in the stomach region was evaluated by ultrasound imaging, which revealed a soft tissue mass or thickening of the mid-region of the posterior wall of the stomach (3.3 cm X 1.6 cm). A CT scan of the chest was also performed to rule out metastasis, and it revealed multiple nodular lesions in both lung fields (most likely secondary) as well as tiny subcentric lymphnodes in the lower pre- and right paratracheal regions after nearly one month of RAIT when the patient was stable for examination. EBRT is still under consideration as adjuvant therapy. Tyrosine kinase inhibitors (TKI) may be considered in cases of refractoriness to radioiodine and disease progression. Bangladesh J. Nuclear Med. 26(1): 67-70, 2023

Deep learning of renal scans in children with antenatal hydronephrosis

Antenatal hydronephrosis (ANH) is one of the most common anomalies identified on prenatal ultrasound, found in up to 4.5% of all pregnancies. Children with ANH are surveilled with repeated renal ultrasound and when there is high suspicion for a ureteropelvic junction obstruction on renal ultrasound, a mercaptuacetyltriglycerine (MAG3) Lasix renal scan is performed to evaluate for obstruction. However, the challenging interpretation of MAG3 renal scans places patients at risk of misdiagnosis. Our objective was to analyze MAG3 renal scans using machine learning to predict renal complications. We hypothesized that our deep learning model would extract features from MAG3 renal scans that can predict renal complications in children with ANH. We performed a case-control study of MAG3 studies drawn from a population of children with ANH concerning for ureteropelvic junction obstruction evaluated at our institution from January 2009 until June of 2021. The outcome was renal complications that occur ≥6 months after an equivocal MAG-3 renal scan. We created two machine learning models: a deep learning model using the radiotracer concentration versus time data from the kidney of interest and a random forest model created using clinical data. The performance of the models was assessed using measures of diagnostic accuracy. We identified 152 eligible patients with available images of which 62 were cases and 90 were controls. The deep learning model predicted future renal complications with an overall accuracy of 73% (95% confidence inteveral [CI] 68-76%) and an AUC of 0.78 (95% CI 0.7, 0.84). The random forest model had an accuracy of 62% (95% CI 60-66%) and an AUC of 0.67 (95% CI. 0 64, 0.72) DISCUSSION: Our deep learning model predicted patients at high risk of developing renal complications following an equivocal renal scan and discriminate those at low risk with moderately high accuracy (73%). The deep learning model outperformed the clinical model built from clinical features classically used by urologists for surgical decision making. Our models have the potential to influence clinical decision making by providing supplemental analytical data from MAG3 scans that would not otherwise be available to urologists. Future multi-institutional retrospective and prospective trials are needed to validate our model.

Coexistent Papillary Thyroid Carcinoma in a Patient with Graves' Disease

A 21-year-old male presented with the features of thyrotoxicosis, and his thyroid function tests revealed primary hyperthyroidism. He also had mild bilateral exophthalmos with lid lag, lid retraction, and a clinical activity score of 1, suggestive of mild Graves' ophthalmopathy. Neck ultrasonography revealed mild diffuse goiter with bilateral fairly large nodules predominantly at the right lobe and bilateral multiple cervical lymphadenopathies. Tc-99m pertechnetate scan demonstrated diffuse goiter with homogeneously increased radiotracer concentration. He had an elevated titer of thyroid-stimulating hormone receptor autoantibody level. Fine-needle aspiration cytology from the largest nodule of the right lobe reported a Bethesda Category-VI lesion compatible with papillary thyroid carcinoma. Graves' disease and papillary thyroid cancer carcinoma might be present concomitantly in the same patient. Although links between these entities have long been investigated, a clear correlation is not established yet.

Radiotracer studies to isolate in-house receptors from poultry liver for multi-chemical hazard analysis in selected food and feed

In-house receptors (IHRs) were isolated from non-immunized poultry liver to analyze selected contaminants and residues in targeted food and feed using 14C- and 3H-labeled radiotracers. Matrix (2 g) was homogenized and centrifuged with the resultant pellet used as IHRs. These were characterized for total protein contents (6.1 mg mL−1) and compared with commercial receptors for aflatoxins (0.28 mg tablet−1) and chloramphenicol (0.12 mg tablet−1). Gel electrophoresis of the IHRs showed a mixture of polypeptides—an important attribute for multi-residues analysis—compared with commercial receptors that presented specific protein bands at 65 kDa (chloramphenicol) and 70 kDa (aflatoxins). The inhibition index of IHRs for aflatoxins B1 and B2 in wheat and bovine feed and chloramphenicol in bovine tissue at, above, and below maximum limits or minimum required performance limits, revealed an inverse relationship between radiotracer and analyte concentrations. Saturation with increased radioligand concentration up to 5.5 kBq indicated higher holding potential. However, increasing incubation time to 30 min did not significantly increase analyte-binding. The IHRs performance was comparable to commercial receptors with control point averages of 348, 410, 555, and 307 counts per minute determined for gentamicin, chloramphenicol, oxytetracycline, and aflatoxin M1, respectively in local milk samples.

Monte Carlo Simulation and Reconstruction: Assessment of Myocardial Perfusion Imaging of Tracer Dynamics With Cardiac Motion Due to Deformation and Respiration Using Gamma Camera With Continuous Acquisition.

PurposeMyocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) is routinely used for stress testing in nuclear medicine. Recently, our group extended its potential going from 3D visual qualitative image analysis to 4D spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration and the estimated myocardial blood flow (MBF) and coronary flow reserve (CFR). However, the quality of reconstructed image is compromised due to cardiac deformation and respiration. The work presented here develops an algorithm that reconstructs the dynamic sequence of separate respiratory and cardiac phases and evaluates the algorithm with data simulated with a Monte Carlo simulation for the continuous image acquisition and processing with a slowly rotating SPECT camera.MethodsA clinically realistic Monte Carlo (MC) simulation is developed using the 4D Extended Cardiac Torso (XCAT) digital phantom with respiratory and cardiac motion to model continuous data acquisition of dynamic cardiac SPECT with slowly rotating gamma cameras by incorporating deformation and displacement of the myocardium due to cardiac and respiratory motion. We extended our previously developed 4D maximum-likelihood expectation-maximization (MLEM) reconstruction algorithm for a data set binned from a continuous list mode (LM) simulation with cardiac and respiratory information. Our spatiotemporal image reconstruction uses splines to explicitly model the temporal change of the tracer for each cardiac and respiratory gate that delineates the myocardial spatial position as the tracer washes in and out. Unlike in a fully list-mode data acquisition and reconstruction the accumulated photons are binned over a specific but very short time interval corresponding to each cardiac and respiratory gate. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it continuously deforms. These results are then compared with the conventional 4D spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. Mean Stabilized Activity (MSA), signal to noise ratio (SNR) and Bias for the myocardium activities for three different target-to-background ratios (TBRs) are evaluated. Dynamic quantitative indices such as wash-in (K1) and wash-out (k2) rates at each gate were also estimated.ResultsThe MSA and SNR are higher with higher TBRs while biases were improved with higher TBRs to less than 10%. The correlation between exhalation-inhalation sequence with the ground truth during respiratory cycle was excellent. Our reconstruction method showed better resolved myocardial walls during diastole to systole as compared to the ungated 4D image. Estimated values of K1 and k2 were also consistent with the ground truth.ConclusionThe continuous image acquisition for dynamic scan using conventional two-head gamma cameras can provide valuable information for MPI. Our study demonstrated the viability of using a continuous image acquisition method on a widely used clinical two-head SPECT system. Our reconstruction method showed better resolved myocardial walls during diastole to systole as compared to the ungated 4D image. Precise implementation of reconstruction algorithms, better segmentation techniques by generating images of different tissue types and background activity would improve the feasibility of the method in real clinical environment.

Computational modeling of PET tracer distribution in solid tumors integrating microvasculature

BackgroundWe present computational modeling of positron emission tomography radiotracer uptake with consideration of blood flow and interstitial fluid flow, performing spatiotemporally-coupled modeling of uptake and integrating the microvasculature. In our mathematical modeling, the uptake of fluorodeoxyglucose F-18 (FDG) was simulated based on the Convection–Diffusion–Reaction equation given its high accuracy and reliability in modeling of transport phenomena. In the proposed model, blood flow and interstitial flow are solved simultaneously to calculate interstitial pressure and velocity distribution inside cancer and normal tissues. As a result, the spatiotemporal distribution of the FDG tracer is calculated based on velocity and pressure distributions in both kinds of tissues.ResultsInterstitial pressure has maximum value in the tumor region compared to surrounding tissue. In addition, interstitial fluid velocity is extremely low in the entire computational domain indicating that convection can be neglected without effecting results noticeably. Furthermore, our results illustrate that the total concentration of FDG in the tumor region is an order of magnitude larger than in surrounding normal tissue, due to lack of functional lymphatic drainage system and also highly-permeable microvessels in tumors. The magnitude of the free tracer and metabolized (phosphorylated) radiotracer concentrations followed very different trends over the entire time period, regardless of tissue type (tumor vs. normal).ConclusionOur spatiotemporally-coupled modeling provides helpful tools towards improved understanding and quantification of in vivo preclinical and clinical studies.

A new cardiac phantom for dynamic SPECT

BackgroundIn recent years, with the advance of myocardial blood flow (MBF) measurement capability in dynamic single photon emission computerized tomography (SPECT) systems, significant effort has been devoted to validation of the new capability. Unfortunately, the mechanical phantoms available for the validation process lack essential features—they either have a constant radiotracer concentration or they have rigid (static) walls unable to simulate cardiac beating. Methods and ResultsWe have developed a mechanical cardiac phantom that is able to mimic physiological radiotracer variation in the left ventricle (LV) cavity and in the myocardium (M), while performing beating-like motion. We have also developed a mathematical model of the phantom, allowing a description of the radiotracer concentrations in both regions (LV, M) as a function of time, which served as a tool for experiment planning and to accurately mimic physiological-like time-activity curves (TACs). A net retention model for the phantom was also developed, which served to compute the theoretical (i.e., expected) MBF of the phantom from measured quantities only, and thus validate the MBF reported by the SPECT system. In this paper, phantom experiments were performed on a GE Discovery NM 530c SPECT system. ConclusionsA novel dynamic cardiac phantom for emission tomography has been developed. The new phantom is capable of producing a wide range of TACs that can mimic physiological (and potentially in the future, pathological) curves, similar to those observed in dynamic SPECT systems. SPECT-reported MBF values were validated against known (measured) activity of the injected radiotracer from phantom experiments, which allowed to determine the accuracy of the GE Discovery 530c SPECT system.

Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

Purpose(S)-4-(3-18F-Fluoropropyl)-ʟ-Glutamic Acid ([18F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system xC-, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [18F]FSPG production are required. Here, we report a cassette-based method to produce [18F]FSPG at high radioactivity concentrations from low amounts of starting activity.ProceduresAn automated synthesis and purification of [18F]FSPG was developed using the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [18F]FSPG and by assessing radiochemical purity using radio-HPLC. Purification of [18F]FSPG was conducted by trapping and washing of the radiotracer on Oasis MCX SPE cartridges, followed by a reverse elution of [18F]FSPG in phosphate-buffered saline. Subsequently, the [18F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.ResultsThe optimized protocol produced [18F]FSPG in 38.4 ± 2.6 % radiochemical yield and >96 % radiochemical purity with a molar activity of 11.1 ± 7.7 GBq/μmol. Small alterations, including the implementation of a reverse elution and an altered Hypercarb cartridge, led to significant improvements in radiotracer concentration from <10 MBq/ml to >100 MBq/ml. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [18F]Fluoride.ConclusionsWe have developed a robust and facile method for [18F]FSPG radiosynthesis in high radiotracer concentration, radiochemical yield, and radiochemical purity. This cassette-based method enabled the production of [18F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of a cassette-based radiosynthesis on an automated synthesis module routinely used for clinical production makes the method amenable to rapid and widespread clinical translation.

Incidental Diffuse Sclerosing Variant Papillary Thyroid Cancer in Grave’s Disease

The diffuse sclerosing variant papillary thyroid carcinoma (DSPTC) is an uncommon form of this neoplasm. Some studies describe its high propensity for tumor invasion, metastasis, and mortality compared with classic papillary thyroid carcinoma. Histologic features of DSPTC may resemble diffuse inflammation as seen with Grave’s or Hashimoto’s thyroiditis, which makes initial diagnosis challenging.A 27-year-old female with Noonan’s Syndrome was evaluated on an outpatient basis after developing atrial fibrillation de novo. Thyroid function tests were consistent with hyperthyroidism with TSH: <0.005 (n: 0.300-3.000 uIU/mL), FT4: 3.59 (0.71-1.85 ng/mL) and FT3: 16.77 (n: 2.0-7.0 pmol/L). Diffuse goiter was noted on physical exam, but no ophthalmopathy or dermopathy was present. TRAB and TSI were elevated at 38.4 (n: <16%) and 423% (n: <140%) respectively. A twenty-four-hour radioiodine uptake was 48% (n:10-35%) and described as essentially homogenous with two foci of decreased radiotracer concentration suggestive of cold nodules. Thyroid ultrasound showed diffuse nodularity bilaterally with associated clusters of calcifications and no discrete nodules. No abnormal appearing lymph nodes were identified. Fine-needle aspiration of both nodular areas was positive for DSPTC. Total thyroidectomy with central neck dissection was performed. Gross and microscopic post-surgical pathology confirmed the presence of diffuse sclerosing papillary thyroid cancer, along with local metastasis to one central lymph node. Patient was scheduled for radioactive iodine therapy.Diffuse sclerosing variant is considered an aggressive histotype of papillary thyroid cancer. Ultrasound features include diffuse scattered microcalcifications with or without discrete nodules that may be confused with chronic inflammatory changes. Despite the limited number of cases, DSPTC is recognized to have specific characteristics, a high female to male ratio, and a young patient age. DSPTC has a high potential for aggressive biologic behavior if not treated promptly at the time of diagnosis. When suspected, total thyroidectomy with lymph node excision followed by radioiodine therapy has been proposed as the correct management to decrease the risk of persistent or recurrent disease.

Validation of kinetic modeling of [15O]H2O PET using an image derived input function on hybrid PET/MRI

In present study we aimed to validate the use of image-derived input functions (IDIF) in the kinetic modeling of cerebral blood flow (CBF) measured by [15O]H2O PET by comparing with the accepted reference standard arterial input function (AIF). Additional comparisons were made to mean cohort AIF and CBF values acquired by methodologically independent phase-contrast mapping (PCM) MRI.Using hybrid PET/MRI an IDIF was generated by measuring the radiotracer concentration in the internal carotid arteries and correcting for partial volume effects using the intravascular volume measured from MRI-angiograms.Seven patients with carotid steno-occlusive disease and twelve healthy controls were examined at rest, after administration of acetazolamide, and, in the control group, during hyperventilation. Agreement between the techniques was examined by linear regression and Bland-Altman analysis.Global CBF values modeled using IDIF correlated with values from AIF across perfusion states in both patients (p<10−6, R2=0.82, 95% limits of agreement (LoA)=[-11.3–9.9] ml/100 g/min) and controls (p<10−6, R2=0.87, 95% LoA=[-17.1–13.7] ml/100 g/min). The reproducibility of gCBF using IDIF was identical to AIF (15.8%). Values from IDIF and AIF had equally good correlation to measurements by PCM MRI, R2=0.86 and R2=0.84, (p<10−6), respectively. Mean cohort AIF performed substantially worse than individual IDIFs (p<10−6, R2=0.63, LoA=[-12.8–25.3] ml/100 g/min). In the patient group, use of IDIF provided similar reactivity maps compared to AIF.In conclusion, global CBF values modeled using IDIF correlated with values modeled by AIF and similar perfusion deficits could be established in a patient group.

Influence of 99m-Tc-Nanocolloid Activity Concentration on Sentinel Lymph Node Detection in Endometrial Cancer: A Quantitative SPECT/CT Study.

This study evaluates quantitative combined single photon emission tomography/computed x-ray tomography (SPECT/CT) to assess the influence of radiotracer concentration on detection of sentinel lymph nodes (SLN) in endometrial cancer (EC). Eighty EC patients underwent pericervical 99m-Tc-nanocolloid injection followed by SPECT/CT. The subgroup of patients with failed SLN detection in SPECT/CT (n = 20) was compared to match-paired patients showing at least two SLNs. Results of intraoperative gamma probe measurements and quantitative SPECT/CT were used for comparison. In patients with detection failure, the percentage of injected dose, absolute activity, and volume of the injection site were significantly lower (30 ± 24% vs. 55 ± 19%; p = 0.01, 43 ± 36 MBq vs. 73 ± 33 MBq; p = 0.04, and 183 ± 164 mL vs. 266 ± 164 mL; p = 0.03) while mean activity concentration in liver, spleen, and bone marrow was significantly higher (p = 0.02). Activity concentration (>33 KBq/mL) and absolute activity (>73 MBq) of injection areas correlated with successful intraoperative SLN detection. In a subgroup of 19 SLNs, a correlation between SPECT/CT-derived uptake and intraoperative count rate was found (R2 = 0.8; p < 0.001). SLN detection in EC patients depended on high radiotracer activity at the cervical injection site. Quantitative SPECT/CT could predict successful intraoperative SLN detection and may help to optimize injection technique.

Digital Solid-State SPECT/CT Quantitation of Absolute 177Lu Radiotracer Concentration: In Vivo and In Vitro Validation.

The accuracy of 177Lu radiotracer concentration measurements using quantitative clinical software was determined by comparing in vivo results for a digital solid-state cadmium-zinc-telluride SPECT/CT system with in vitro sampling. Methods: First, image acquisition parameters were assessed for an International Electrotechnical Commission body phantom emulating clinical count rates loaded with a lung insert and 6 hot spheres with a 12:1 target-to-background ratio of 177Lu solution. Then, the data of 28 whole-body SPECT/CT scans of 7 patients who underwent 177Lu prostate-specific membrane antigen radioligand therapy were retrospectively analyzed. Three users analyzed SPECT/CT images for in vivo urinary bladder radiotracer uptake using quantitative software. In vitro radiopharmaceutical concentrations were calculated using urine sampling obtained immediately after each scan, scaled to SUVs. Any in vivo or in vitro identity relations were determined by linear regression (ideally, slope = 1 and intercept = 0), within a 95% confidence interval. Results: Phantom results demonstrated lower quantitative error for acquisitions using the 113-keV 177Lu energy peak rather than including the 208-keV peak, given that only low-energy collimation was available in this camera configuration. In the clinical study, 24 in vivo-in vitro pairs were eligible for further analysis, with 4 having been rejected as outliers (via Cook distance calculations). All linear regressions (R2 ≥ 0.82, P < 0.0001) provided identity in vivo-in vitro relations (95% confidence interval), with SUV averages from all users giving a slope of 0.96 ± 0.13, an intercept of -0.07 ± 0.46 g/mL, and an average residual difference of 19.5%. In acquisitions with the lower-energy 177Lu energy peak, solid-state SPECT/CT imaging provided an accuracy to within approximately 20% of in vivo urinary bladder radiotracer concentrations. Conclusion: This noninvasive in vivo quantitation method can potentially improve diagnosis, patient management, and treatment response assessment and provide data essential to 177Lu dosimetry.