SPECT Imaging Research Articles

90Y SPECT scatter estimation and voxel dosimetry in radioembolization using a unified deep learning framework

Purpose90Y SPECT-based dosimetry following radioembolization (RE) in liver malignancies is challenging due to the inherent scatter and the poor spatial resolution of bremsstrahlung SPECT. This study explores a deep-learning-based absorbed dose-rate estimation method for 90Y that mitigates the impact of poor SPECT image quality on dosimetry and the accuracy–efficiency trade-off of Monte Carlo (MC)-based scatter estimation and voxel dosimetry methods.MethodsOur unified framework consists of three stages: convolutional neural network (CNN)-based bremsstrahlung scatter estimation, SPECT reconstruction with scatter correction (SC) and absorbed dose-rate map generation with a residual learning network (DblurDoseNet). The input to the framework is the measured SPECT projections and CT, and the output is the absorbed dose-rate map. For training and testing under realistic conditions, we generated a series of virtual patient phantom activity/density maps from post-therapy images of patients treated with 90Y-RE at our clinic. To train the scatter estimation network, we use the scatter projections for phantoms generated from MC simulation as the ground truth (GT). To train the dosimetry network, we use MC dose-rate maps generated directly from the activity/density maps of phantoms as the GT (Phantom + MC Dose). We compared performance of our framework (SPECT w/CNN SC + DblurDoseNet) and MC dosimetry (SPECT w/CNN SC + MC Dose) using normalized root mean square error (NRMSE) and normalized mean absolute error (NMAE) relative to GT.ResultsWhen testing on virtual patient phantoms, our CNN predicted scatter projections had NRMSE of 4.0% ± 0.7% on average. For the SPECT reconstruction with CNN SC, we observed a significant improvement on NRMSE (9.2% ± 1.7%), compared to reconstructions with no SC (149.5% ± 31.2%). In terms of virtual patient dose-rate estimation, SPECT w/CNN SC + DblurDoseNet had a NMAE of 8.6% ± 5.7% and 5.4% ± 4.8% in lesions and healthy livers, respectively; compared to 24.0% ± 6.1% and 17.7% ± 2.1% for SPECT w/CNN SC + MC Dose. In patient dose-rate maps, though no GT was available, we observed sharper lesion boundaries and increased lesion-to-background ratios with our framework. For a typical patient data set, the trained networks took ~ 1 s to generate the scatter estimate and ~ 20 s to generate the dose-rate map (matrix size: 512 × 512 × 194) on a single GPU (NVIDIA V100).ConclusionOur deep learning framework, trained using true activity/density maps, has the potential to outperform non-learning voxel dosimetry methods such as MC that are dependent on SPECT image quality. Across comprehensive testing and evaluations on multiple targeted lesions and healthy livers in virtual patients, our proposed deep learning framework demonstrated higher (66% on average in terms of NMAE) estimation accuracy than the current “gold-standard” MC method. The enhanced computing speed with our framework without sacrificing accuracy is highly relevant for clinical dosimetry following 90Y-RE.

99mTc-DMSA renal cortical scanning: a comparison of planar, SPECT, and SPECT/CT imaging for the detection of renal cortical scarring

BackgroundThe best way to assess renal cortical scarring is planar scintigraphy with 99mTc-dimercaptosuccinic acid (DMSA), while the value of single-photon emission computed tomography/computed tomography (SPECT/CT) is not well validated. The aim of the present study was to assess the value of planar, SPECT, and SPECT/CT scanning using 99mTc-DMSA in detecting renal cortical scarring.MethodsPatients with clinically suspected renal cortical scar were included in this prospective cohort. 99mTc-DMSA Planar images were obtained approximately 3–4 h after intravenous injection (IV) of 185 MBq of the tracer. SPECT/CT scans were obtained immediately after the planar ones. An expert nuclear medicine doctor who was unaware of the patient's clinical history or any previous imaging results analyzed the images. Each kidney was given a score of 0 for no obvious defects, 1 for equivocal lesions, 2 for a single defect, 3 for several defects, and 4 for non-visualized/non-functioning kidney (in CT images). The results of each method were then compared to each other.ResultsOne hundred eighty-six kidneys from ninety-three individuals were eligible for assessment. Planar scans detected 21 kidneys with equivocal lesions, 5 with single and 7 with multiple defects. SPECT scans detected 17 kidneys with single and 40 with multiple defects, while SPECT/CT scans revealed 5 with single and 11 with multiple defects. Only 5 of the 17 kidneys with single defects diagnosed by SPECT imaging had a scar in the SPECT/CT scans, whereas the remaining 12 had a solitary cortical cyst in the CT images. Only 11 of 40 kidneys with multiple defects on SPECT were shown to have a scar in the corresponding SPECT/CT images, whereas the rest matched to either hydro-nephrotic changes or multiple cortical cysts. Four kidneys with multiple defects on the SPECT/CT images were normal in the planar readings, were ascribed to an increase in renal background activity and a reduction in renal function.ConclusionsIn cases with suspected renal cortical scar, 99mTc-DMSA SPECT/CT scanning outperformed both planar and SPECT imaging by reducing the number of false-positive SPECT readings and false-negative planar readings.

Radiolabeling of Platelets with 99mTc-HYNIC-Duramycin for In Vivo Imaging Studies

Following the in vivo biodistribution of platelets can contribute to a better understanding of their physiological and pathological roles, and nuclear imaging methods, such as single photon emission tomography (SPECT), provide an excellent method for that. SPECT imaging needs stable labeling of the platelets with a radioisotope. In this study, we report a new method to label platelets with 99mTc, the most frequently used isotope for SPECT in clinical applications. The proposed radiolabeling procedure uses a membrane-binding peptide, duramycin. Our results show that duramycin does not cause significant platelet activation, and radiolabeling can be carried out with a procedure utilizing a simple labeling step followed by a size-exclusion chromatography-based purification step. The in vivo application of the radiolabeled human platelets in mice yielded quantitative biodistribution images of the spleen and liver and no accumulation in the lungs. The performed small-animal SPECT/CT in vivo imaging investigations revealed good in vivo stability of the labeling, which paves the way for further applications of 99mTc-labeled-Duramycin in platelet imaging.

Development of novel radiolabeled antibody-conjugated graphene quantum dots for targeted in vivo breast cancer imaging and biodistribution studies

Nanotechnology-based drug delivery platforms have emerged as one of the promising approaches for the diagnosis and treatment of cancers. Furthermore, significant advancements have been achieved in the development of nanoparticle-antibody conjugates for applications in tumor imaging and immunoassays. Without a doubt, the diagnostic insight garnered from these nanoprobes will prove invaluable in determining rational therapeutic strategies. In the current experiment, we developed a breast cancer imaging probe utilizing graphene quantum dots, these quantum dots were conjugated with pembrolizumab (GQDs–pembrolizumab), a human monoclonal antibody (mAb) targeting the immune checkpoint programmed death receptor (PD-1) and its programmed death ligand-1 (PD-L1). Various techniques were employed for characterization, encompassing transmission electron microscopy (TEM), element mapping, atomic force microscopy (AFM), Fourier-transform infrared spectroscopy, and circular dichroism (CD) spectroscopy. The toxicity of nanoconjugate was evaluated using the MTT assay on HEK-293 and 4T1 cell lines. Subsequently, the synthesized nanoconjugate was radiolabeled with Technetium-99m (99mTc) to produce 99mTc-GQDs–pembrolizumab. Biodistribution and SPECT imaging were conducted to assess the pharmacokinetics and targeting efficacy of the 99mTc-GQDs–pembrolizumab in a BALB/c mouse model bearing with 4T1 tumors. The high Radiochemical purity (RCP > 95 %) and satisfactory in vitro stability demonstrate the significant potential of GQDs–pembrolizumab to form complexes with Technetium-99m. The findings from imaging and biodistribution studies demonstrated the high activity of 99mTc-GQDs–pembrolizumab at the tumor site (8.4 %ID/g), attributed to the presence of the PD-1 receptor. Furthermore, the increased radiotracer uptake was evident in the liver and spleen, both being lymphoid tissues. The suitable properties and behavior of 99mTc-GQDs–pembrolizumab suggest that it holds promise as a novel probe for the development of radiopharmaceutical-based immune checkpoint monoclonal antibodies. Additionally, it has the potential to facilitate immunotherapy for treating a wide range of cancers.

Abstract A068: Site-specific modification of nanobodies for ImmunoPET of Liver Cancer utilizing Self-labeling nanobody-tag pair (SLANT) technology

Abstract Visualization of tumor cells is critical in diagnosing, monitoring, and treating patients with cancer. Liver cancer has an 18 percent 5-year survival rate and is the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC), the most common type of liver cancer, only takes up 18F-fluorodeoxyglucose (18F-FDG), the most commonly used clinical positron emission tomography (PET) tracer, 50% of the time. As such, developing an HCC-selective imaging agent could improve our ability for earlier diagnosis, post-treatment surveillance, and ability to increase patient longevity and quality of life. Single domain antibodies (sdAbs), or nanobodies (Nb), are attractive scaffolds for radiopharmaceutical development because of their high target affinity and specificity, ready availability from recombinant expression in bacteria, and small size for rapid clearance, better tumor penetration, and same-day imaging. However, conventional conjugation chemistry that exploits cysteines or lysines found on the native protein can abrogate the binding site of the smaller Nbs. We have previously used sortase A-based site-specific conjugation to address these challenges; however, improvements were still possible. Here, we developed a novel self-labeling Nb-tag pair (SLANT) that allows fast and specific covalent labeling of a Nb based on peptide epitope binding. We used SLANT to engineer a heterodimeric Nb construct consisting of a Nb (HN3) specific for Glypican-3, a heparin sulfate proteoglycan that is overexpressed in 75-90% of all HCCs and our self-labeling Nb. This design allows for site-specific labeling of the heterodimeric (GPC3-specific) construct in a manner that avoids modification of the tumor antigen-specific protomer. Labeling is achieved via exposure of the fusion protein to a crosslinking peptide functionalized with a chelator (DOTA). This methodology produces labeled protein at over 90 percent yields within minutes compared to less than 30 percent yields utilizing enzymatic methods. Biolayer interferometry and radioligand saturation studies were done to determine the binding affinity of the conjugate for GPC3 pre- and post-Indium-111 labeling. SPECT/CT and biodistribution studies were done at 1h, 3hrs, and 24hrs with HepG2 and HepG2-GPC3- xenografts to assess conjugate specificity and ability to accumulate in GPC3+ liver tumors. Our conjugate exhibited a nanomolar affinity for GPC3 in vitro (17-36 nM). SPECT/CT and biodistribution studies showed specificity for GPC3 in HepG2 liver cancer xenografts (~5.5% IA/g at 1-hour post-injection (p.i.)) and minimal uptake in HepG2 GPC3- tumors (~0.62% IA/g at 1-hour p.i.). Our results highlight the development of a new labeling paradigm applied to GPC3+ liver cancer. This approach can be used for same-day imaging and the rapid development of SPECT and PET imaging tracers for different cellular markers on cancer cells, addressing known tumor heterogeneity. Citation Format: Stanley Fayn, Chino C Cabalteja, Woonghee Lee, Divya Nambiar, Kwamena E Baidoo, Freddy E Escorcia, Ross W Cheloha. Site-specific modification of nanobodies for ImmunoPET of Liver Cancer utilizing Self-labeling nanobody-tag pair (SLANT) technology [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A068.

Preclinical Evaluation of a Radiotheranostic Single-Domain Antibody Against Fibroblast Activation Protein α.

Fibroblast activation protein α (FAP) is highly expressed on cancer-associated fibroblasts of epithelial-derived cancers. Breast, colon, and pancreatic tumors often show strong desmoplastic reactions, which result in a dominant presence of stromal cells. FAP has gained interest as a target for molecular imaging and targeted therapies. Single-domain antibodies (sdAbs) are the smallest antibody-derived fragments with beneficial pharmacokinetic properties for molecular imaging and targeted therapy. Methods: We describe the generation, selection, and characterization of a sdAb against FAP. In mice, we assessed its imaging and therapeutic potential after radiolabeling with tracer-dose 131I and 68Ga for SPECT and PET imaging, respectively, and with 131I and 225Ac for targeted radionuclide therapy. Results: The lead sdAb, 4AH29, exhibiting picomolar affinity for a distinct FAP epitope, recognized both purified and membrane-bound FAP protein. Radiolabeled versions, including [68Ga]Ga-DOTA-4AH29, [225Ac]Ac-DOTA-4AH29, and [131I]I-guanidinomethyl iodobenzoate (GMIB)-4AH29, displayed radiochemical purities exceeding 95% and effectively bound to recombinant human FAP protein and FAP-positive GM05389 human fibroblasts. These radiolabeled compounds exhibited rapid and specific accumulation in human FAP-positive U87-MG glioblastoma tumors, with low but specific uptake in lymph nodes, uterus, bone, and skin (∼2-3 percentage injected activity per gram of tissue [%IA/g]). Kidney clearance of unbound [131I]I-GMIB-4AH29 was fast (<1 %IA/g after 24 h), whereas [225Ac]Ac-DOTA-4AH29 exhibited slower clearance (8.07 ± 1.39 %IA/g after 24 h and 2.47 ± 0.18 %IA/g after 96 h). Mice treated with [225Ac]Ac-DOTA-4AH29 and [131I]I-GMIB-4AH29 demonstrated prolonged survival compared with those receiving vehicle solution. Conclusion: [68Ga]Ga-DOTA-4AH29 and [131I]I-GMIB-4AH29 enable precise FAP-positive tumor detection in mice. Therapeutic [225Ac]Ac-DOTA-4AH29 and [131I]I-GMIB-4AH29 exhibit strong and sustained tumor targeting, resulting in dose-dependent therapeutic effects in FAP-positive tumor-bearing mice, albeit with kidney toxicity observed later for [225Ac]Ac-DOTA-4AH29. This study confirms the potential of radiolabeled sdAb 4AH29 as a radiotheranostic agent for FAP-positive cancers, warranting clinical evaluation.

The prioritization of biomarkers in the diagnostic workup of Lewy body disease

AbstractThe term Lewy body disease (LBD) encompasses a spectrum of neurodegenerative conditions, particularly Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB), associated with abnormal deposits of alpha‐synuclein in the brain and representing up to 20% of all neurocognitive disorders in memory clinics. Mild cognitive impairment or mild dementia precede or concur with Parkinsonism in the early stages of DLB and in a third of patients with PD at diagnosis. However, when Parkinsonism is slightly detectable, the differential diagnosis from other dementing conditions, such as Alzheimer’s disease (AD), may be challenging. For this reason, neuroimaging and electrophysiological biomarkers, divided into indicative or supportive based on their diagnostic performance over or below 80%, assist the clinical reasoning to increase the likelihood that MCI/early dementia is associated with LB. The European Intersociety Consensus Diagnostic Task Force recommends prioritizing the Dopamine transporter (DaT)‐SPECT imaging to investigate nigro‐striatal degeneration as the first biomarker (sensitivity 76%, specificity 88%), and suggests subsequently [123I]‐MIBG cardiac scintigraphy to evaluate the postganglionic sympathetic denervation in those cases (about a quarter) where DaT‐SPECT is negative but DLB is still clinically possible (AD pathology is estimated to be underlying in about 86% of these cases). In the absence of well‐validated techniques to establish the presence of brain alpha‐synuclein aggregates in vivo, the proposed sequence of biomarkers will provide the most accurate and cost‐effective biomarker‐based diagnosis of LBD.

Deep learning-based attenuation correction method in 99mTc-GSA SPECT/CT hepatic imaging: a phantom study.

This study aimed to evaluate a deep learning-based attenuation correction (AC) method to generate pseudo-computed tomography (CT) images from non-AC single-photon emission computed tomography images (SPECTNC) for AC in 99mTc-galactosyl human albumin diethylenetriamine pentaacetic acid (GSA) scintigraphy and to reduce patient dosage. A cycle-consistent generative network (CycleGAN) model was used to generate pseudo-CT images. The training datasets comprised approximately 850 liver phantom images obtained from SPECTNC and real CT images. The training datasets were then input to CycleGAN, and pseudo-CT images were output. SPECT images with real-time CT attenuation correction (SPECTCTAC) and pseudo-CT attenuation correction (SPECTGAN) were acquired. The difference in liver volume between real CT and pseudo-CT images was evaluated. Total counts and uniformity were then used to evaluate the effects of AC. Additionally, the similarity coefficients of SPECTCTAC and SPECTGAN were assessed using a structural similarity (SSIM) index. The pseudo-CT images produced a lower liver volume than the real CT images. SPECTCTAC exhibited a higher total count than SPECTNC and SPECTGAN, which were approximately 60% and 7% lower, respectively. The uniformities of SPECTCTAC and SPECTGAN were better than those of SPECTNC. The mean SSIM value for SPECTCTAC and SPECTGAN was 0.97. We proposed a deep learning-based AC approach to generate pseudo-CT images from SPECTNC images in 99mTc-GSA scintigraphy. SPECTGAN with AC using pseudo-CT images was similar to SPECTCTAC, demonstrating the possibility of SPECT/CT examination with reduced exposure to radiation.

The chicken chorioallantoic membrane as a low-cost, high-throughput model for cancer imaging

Mouse models are invaluable tools for radiotracer development and validation. They are, however, expensive, low throughput, and are constrained by animal welfare considerations. Here, we assessed the chicken chorioallantoic membrane (CAM) as an alternative to mice for preclinical cancer imaging studies. NCI-H460 FLuc cells grown in Matrigel on the CAM formed vascularized tumors of reproducible size without compromising embryo viability. By designing a simple method for vessel cannulation it was possible to perform dynamic PET imaging in ovo, producing high tumor-to-background signal for both 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and (4S)-4-(3-18F-fluoropropyl)-L-glutamate (18F-FSPG). The pattern of 18F-FDG tumor uptake were similar in ovo and in vivo, although tumor-associated radioactivity was higher in the CAM-grown tumors over the 60 min imaging time course. Additionally, 18F-FSPG provided an early marker of both treatment response to external beam radiotherapy and target inhibition in ovo. Overall, the CAM provided a low-cost alternative to tumor xenograft mouse models which may broaden access to PET and SPECT imaging and have utility across multiple applications.

The effects of kilovoltage (kV) and milliampere seconds (mAs) values for SPECT attenuation correction: An anthropomorphic phantom study

The purpose of SPECT/CT imaging to be used in dosimetric calculations is to perform accurate attenuation correction by giving the patient the minimum radiation dose. in accordance with ALARA principles (as low as reasonably achievable), it is critical to limit the amount of radiation given to the patient as far as possible in medical fields where radiation therapy is applied. The goal of this study is to determine the optimum kV and mAs values needed to keep the radiation dose that can be given to the patient in CT scans at a minimum level for attenuation correction, as well as to determine the CT-induced radiation doses on patients with different kV and mAs values using an anthropomorphic phantom.Radionuclides 177Lu and 131I were used in SPECT imaging. For CT-based attenuation correction, images were taken with various values between 80 kV × 30 mAs and 140 kV × 300 mAs using the anthropomorphic phantom. After that attenuation correction was performed with the obtained CT images for SPECT images. Then, CT-derived radiation doses were calculated.Our results showed that 80 kV × 30 mAs values can be used in scans after radionuclide treatment for CT attenuation correction. It was determined that the patient was exposed to a radiation dose of 0.432 mSv as a result of the CT scanning with the full detector width area of gamma camera detector. Thus, scanning with these values (80 kV × 30 mAs) resulted in approximately 95% less radiation exposure (0,432 mSv) than the value (9,38 mSv) with scanning of the manufacturer's recommended value (120 kV × 200 mAs).

Perfusion Imaging and Inflammation Biomarkers Provide Complementary Information in Alzheimer's Disease.

Single photon emission tomography (SPECT) can detect early changes in brain perfusion to support the diagnosis of dementia. Inflammation is a driver for dementia progression and measures of inflammation may further support dementia diagnosis. In this study, we assessed whether combining imaging with markers of inflammation improves prediction of the likelihood of Alzheimer's disease (AD). We analyzed 91 participants datasets (Institutional Ethics Approval 20/NW/0222). AD biomarkers and markers of inflammation were measured in cerebrospinal fluid. Statistical parametric mapping was used to quantify brain perfusion differences in perfusion SPECT images. Logistic regression models were trained to evaluate the ability of imaging and inflammation markers, both individually and combined, to predict AD. Regional perfusion reduction in the precuneus and medial temporal regions predicted Aβ42 status. Increase in inflammation markers predicted tau and neurodegeneration. Matrix metalloproteneinase-10, a marker of blood-brain barrier regulation, was associated with perfusion reduction in the right temporal lobe. Adenosine deaminase, an enzyme involved in sleep homeostasis and inflammation, was the strongest predictor of neurodegeneration with an odds ratio of 10.3. The area under the receiver operator characteristic curve for the logistic regression model was 0.76 for imaging and 0.76 for inflammation. Combining inflammation and imaging markers yielded an area under the curve of 0.85. Study results showed that markers of brain perfusion imaging and markers of inflammation provide complementary information in AD evaluation. Inflammation markers better predict tau status while perfusion imaging measures represent amyloid status. Combining imaging and inflammation improves AD prediction.

Theranostic Imaging Surrogates for Targeted Alpha Therapy: Progress in Production, Purification, and Applications.

This article highlights recent developments of SPECT and PET diagnostic imaging surrogates for targeted alpha particle therapy (TAT) radiopharmaceuticals. It outlines the rationale for using imaging surrogates to improve diagnostic-scan accuracy and facilitate research, and the properties an imaging-surrogate candidate should possess. It evaluates the strengths and limitations of each potential imaging surrogate. Thirteen surrogates for TAT are explored: 133La, 132La, 134Ce/134La, and 226Ac for 225Ac TAT; 203Pb for 212Pb TAT; 131Ba for 223Ra and 224Ra TAT; 123I, 124I, 131I and 209At for 211At TAT; 134Ce/134La for 227Th TAT; and 155Tb and 152Tb for 149Tb TAT.

Lu-177-PSMA dosimetry for kidneys and tumors based on SPECT images at two imaging time points.

Personalized dosimetry for Lu-177-PSMA treatment requires multiple-time-point SPECT/CT scans to calculate time-integrated activity (TIA). This study evaluates two-time-point (TTP) methods for TIA calculation for kidneys and tumors. A total of 18 patients treated with 3.7-7.4 GBq Lu-177 PSMA-617 were analyzed retrospectively, including 18 sets of left and right kidneys, as well as 45 tumors. Four quantitative SPECT/CT (4TP) were acquired at 2 h, 20 h, 40 h, 60 h (n = 11), or 200 h (n = 7) after treatment, and they were fit bi-exponentially as reference. The TTP method was fitted by a mono-exponential washout function using two selected imaging time points for kidneys. For tumors, one uptake and one washout phase were modeled, assuming linear (type I) and same (type II) uptake phase between 0 h to the first time point and mono-exponential washout thereafter. Two single-time-point (STP) methods were also implemented for comparison. TIA calculated by TTP and STP methods were compared with reference to the 4TP TIA. For the kidneys, the TTP methods using 20 h-60 h and 40 h-200 h had smaller mean absolute errors of 8.05 ± 6.05% and 4.95 ± 3.98%, respectively, as compared to other combinations of time points and STP methods. For tumors, the type I and type II TTP methods using 20h-60 h and 40-200 h had smaller mean absolute errors of 6.14 ± 5.19% and 12.22 ± 4.44%, and 8.31 ± 7.16% and 4.48 ± 7.10%, respectively, as compared to other TTP and STP methods. The TTP methods based on later imaging time demonstrated fewer errors than the STP methods in kidney and tumor TIA. Imaging at 20 h-60 h and 40 h-200 h could simplify the dosimetry procedures with fewer TIA estimation errors.

NIMG-18. MULTI-PARAMETRIC MRI AND SPECT ASSESSMENT OF TREATMENT DOSE AND EFFICACY IN RESPECT-GBM FOR RECURRENT GLIOBLASTOMA (RGBM)

Abstract BACKGROUND We have previously shown a dose-dependent association with survival for patients receiving Rhenium-186-nanoliposome (186RNL) for rGBM. This study aim, applying 3D-dosimetry and advanced-MRI features to outcome assessment, was to extend those findings. METHODS SPECT/CT images were acquired at mid-fusion, end-of-infusion, 24-hour, 120-hour, and 192-hour post-186RNL infusion. Baseline MRI was performed within 7days of treatment, at 28d, and every 56d until progression with: T1-3D pre-/post-contrast agent, DSC, DWI. SPECT images were processed using MIM software with treatment volumes corresponding to the 100Gy isodose curve exported as treatment-ROI. Difference (delta T1) between standardized pre-contrast (T1) and post-contrast (T1_C) anatomic images were used to measure tumor volume (IB Rad Tech). Within the tumor, various MRI-derived parameters, such as standardized-relative-cerebral-blood-volume (srCBV), time to maximum (Tmax), time to peak (TTP), were calculated. RESULTS Perfusion analysis(n=8) revealed significant decreases in the mean nrCBF, nrCBV, rCBF, rCBV, and srCBV with dose [nrCBF: -0.25 95% CI -0.37 to -0.14, p=0.005, nrCBV: -0.23 95% CI -0.34 to -0.13, p=0.005, rCBF: -3.5 95% CI -5.37 to -1.63, p=0.01, rCBV: -11.91 95% CI -20.45 to -3.38, p=0.03, srCBV: -0.14 95% CI -0.23 to -0.05, p=0.02], and a significant increase in the mean Tmax [1.88 95% CI 0.58 to 3.17, p=0.03]. The mean volume (n=10) not covered by treatment (-1.59 95% CI -4.81 to 1.63, p=0.36), Tumor volume (-0.76 95% CI -5.23 to 3.72, p=0.75), Treated volume (3.31 95% CI -0.44 to 7.06, p=0.12), and Tumor Volume covered by treatment (0.84 95% CI -1.2 to 2.87, p=0.44) did not vary significantly with dose although may gain significance with a larger data set. CONCLUSION MRI radiographic features proved valuable in assessing treatment efficacy and guiding treatment considerations. Image processing is ongoing, and the complete data set will be presented.

The second phase-3 multi-center trial of flurpiridaz F-18 PET myocardial perfusion imaging for coronary artery disease evaluation

Abstract Background/Introduction Flurpiridaz F-18 (flurpiridaz) is a novel PET myocardial perfusion imaging tracer with outstanding imaging characteristics. Purpose To further assess the diagnostic efficacy and safety of flurpiridaz PET for the detection and evaluation of coronary artery disease (CAD) defined as &amp;gt;50% stenosis by quantitative invasive coronary angiography (ICA) in a multi-center prospective international clinical trial. The primary end point was to assess the diagnostic efficacy (sensitivity and specificity) of flurpiridaz PET MPI for the detection of CAD. The secondary end points were to compare the diagnostic performance of flurpiridaz PET vs. Tc-99m SPECT in the detection of CAD in all patients and in the clinically important subgroups of women, obese [body mass index (BMI) ≥30 kg/m2], and diabetics. Also, PET and Tc-99m SPECT were compared for defect severity/extent, image quality, confidence of interpretation and radiation dose to patients. The safety of flurpiridaz PET was also evaluated. Methods 730 patients with suspected CAD from 48 clinical sites in US, Canada and Europe were enrolled. Patients underwent 1-day rest/stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m labeled SPECT before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ICA was quantified by a core laboratory expert blinded to clinical and image data. Results 578 patients (age, 63.7±9.5 years) were evaluable. Flurpiridaz PET met the prespecified primary endpoint of the study; sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers. The secondary endpoints were also met in the overall population, in women, in obese patients, and in diabetics. Flurpiridaz PET ROC area under the curves were significantly higher than SPECT in the overall population (0.80 vs 0.68, p&amp;lt;0.0001), in women (0.84 vs 0.70, p&amp;lt;0.01), and in obese patients (0.79 vs 0.67, p&amp;lt;0.001), but not in diabetics (0.76 vs 0.69, p=0.088). Flurpiridaz PET was also superior to SPECT for assessment of defect extent/severity (p&amp;lt;0.0001). Image quality (% excellent or good) of flurpiridaz PET was significantly better than SPECT for rest images (93% vs 72%, p&amp;lt;0.0001), pharmacological stress images (96% vs 78%, p&amp;lt;0.0001), and treadmill exercise images (97% vs 87%, p&amp;lt;0.05). Radiation exposure, evaluated in 604 dosed patients, was less for PET than same-day rest/stress SPECT using either Tetrofosmin or Sestamibi with 6.25 mSv for flurpiridaz PET, 9.86 mSv for 99mTc-tetrofosmin SPECT and 12.41 mSv for 99mTc-sestamibi SPECT. Conclusion This second flurpiridaz PET myocardial perfusion imaging multicenter international trial demonstrates that flurpiridaz has promise as a new tracer for detection and evaluation of coronary artery disease. This is particularly so in women and patients with BMI≥30.

Abstract 15399: Cardiac Sympathetic Nerve Activity in Women With a History of Takotsubo Syndrome: A Novel Stress Myocardial Radionuclide Imaging Strategy

Introduction: Takotsubo syndrome (TTS) is characterized by transient left ventricular (LV) systolic dysfunction, triggered by physical or emotional stress, and associated with increased long-term cardiovascular morbidity. Cardiac iodine-123-meta-iodobenzylguanidine (mIBG) imaging has previously demonstrated sympathetic hyperactivity in the TTS subacute state which improves at follow-up during rest imaging. Cardiac neuronal dysfunction in response to stress has not been evaluated in recovered TTS. Hypothesis: Sympathetic hyperactivity, as measured by stress mIBG, is abnormal in TTS after recovery of LV ejection fraction (LVEF). Methods: To elicit a sympathetic challenge, women with history of TTS with recovered LVEF (n=19) and asymptomatic age- and sex-matched reference controls (n=10) underwent treadmill (6 minutes) with simultaneous mental-stress testing (public speaking with anger recall). mIBG (10 mCi) was injected during exercise, and planar and SPECT imaging were performed at 15 min (early) and 240 min (late), followed by Tc-99m tetrofosmin myocardial perfusion imaging. Early and late heart-to-mediastinal ratio (HMR) and washout rate (WR) corrected for background were calculated. Results: Median time from last TTS event was 23 months (range 4-56). Overall mean age was 60± 12 years, body mass index 25 ± 4kg/m 2 , resting LVEF 70 ± 7%, 41% hypertension and 0% diabetes with no difference between TTS and controls. TTS had higher resting (140 ± 22 vs 123 ± 19 mmHg, p=0.049) and peak (187 ± 17 vs 171 ± 15 mmHg, p= 0.018) systolic blood pressure. While the early HMR and WR were similar, the late HMR was significantly lower in the TTS group (Figure). Conclusions: Women with a history of TTS have lower late HMR but similar WR, suggesting neuronal dysfunction in response to sympathetic challenge persists long after recovery from TTS event. Further analysis of catecholamine levels and central nervous system neural pathways will explore the mechanism of dysregulation.

P-327 - Optimizing 203Pb cyclotron production and availability: The ideal SPECT imaging theranostic partner for 212Pb targeted alpha therapy

P-327 - Optimizing 203Pb cyclotron production and availability: The ideal SPECT imaging theranostic partner for 212Pb targeted alpha therapy

O-54 - Preclinical evaluation of [155/161Tb]Tb-crown-TATE – a novel SPECT imaging agent targeting neuroendocrine tumors

O-54 - Preclinical evaluation of [155/161Tb]Tb-crown-TATE – a novel SPECT imaging agent targeting neuroendocrine tumors

P-153 - Performance assessment of quantitative preclinical SPECT imaging with 155Tb and 161Tb

P-153 - Performance assessment of quantitative preclinical SPECT imaging with 155Tb and 161Tb

Diffuse Cardiac Uptake Misdiagnosed as Cardiac Amyloidosis in Bone Scan.

In this presented case, a 77-year-old woman with an implanted prosthesis and ongoing knee pain underwent a bone scan using 99mTc-hydroxydiphosphonate (HDP) in suspicion for bone infection. An incidental finding from this scan revealed diffuse cardiac uptake, necessitating further diagnostic procedures to exclude the possibility of cardiac amyloidosis. In the subsequent 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan and SPECT images, no perceptible cardiac uptake was observed at all. Upon retrospective review of the patient's medical records, she received 1000 mg of ferric carboxymaltose for iron-deficient anemia the day before the 99mTc-HDP bone scan. Therefore, it was assumed that the diffuse and temporary cardiac activity was due to the transient iron overload. We present and share these bone scan images in order to avoid possible future misinterpretation of cardiac amyloidosis.