Delayed Positron Emission Tomography Imaging Research Articles

First-in-human infection imaging with 89Zr-labelled leukocytes and comparison of scan quality with [99mTc]Tc-HMPAO-labelled leukocytes.

Nuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 (89Zr) is a positron emitter with a half-life of 78.4 h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [89Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89Zr-labelled leukocytes, using p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99mTc]Tc-HMPAO-labelled leukocytes. Leukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [99mTc]Tc-HMPAO according to standardised methods, and [89Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [99mTc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients. Successful [89Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n = 8). A mean high viability of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [89Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99mTc]Tc-HMPAO- and [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99mTc]Tc-HMPAO-labelled leukocytes outperformed [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel. Although the [89Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [89Zr]Zr-Df-Bz-NCS-labelled leukocytes.

Deep Learning-Based Delayed PET Image Synthesis from Corresponding Early Scanned PET for Dosimetry Uptake Estimation.

The acquisition of in vivo radiopharmaceutical distribution through imaging is time-consuming due to dosimetry, which requires the subject to be scanned at several time points post-injection. This study aimed to generate delayed positron emission tomography images from early images using a deep-learning-based image generation model to mitigate the time cost and inconvenience. Eighteen healthy participants were recruited and injected with [18F]Fluorodeoxyglucose. A paired image-to-image translation model, based on a generative adversarial network (GAN), was used as the generation model. The standardized uptake value (SUV) mean of the generated image of each organ was compared with that of the ground-truth. The least square GAN and perceptual loss combinations displayed the best performance. As the uptake time of the early image became closer to that of the ground-truth image, the translation performance improved. The SUV mean values of the nominated organs were estimated reasonably accurately for the muscle, heart, liver, and spleen. The results demonstrate that the image-to-image translation deep learning model is applicable for the generation of a functional image from another functional image acquired from normal subjects, including predictions of organ-wise activity for specific normal organs.

Delayed PET imaging using image synthesis network and nonrigid registration without additional CT scan.

Attenuation correction is critical for positron emission tomography (PET) image reconstruction. The standard protocol for obtaining attenuation information in a clinical PET scanner is via coregistered computed tomography (CT) images. Therefore, for delayed PET imaging, the CT scan is repeated twice, which increases the radiation dose for the patient. In this paper, we propose a zero-extradose delayed PET imaging method that requires no additional CT scans. A deep learning-based synthesis network is designed to convert PET data into pseudo-CT images for delayed scans. Then, nonrigid registration is performed between this pseudo CT image and the CT image of the first scan, warping the CT image of the first scan to an estimated CT image for the delayed scan. Finally, the PET image attenuation correction in the delayed scan is obtained from this estimated CT image. Experiments with clinical datasets are implemented to assess the effectiveness of the proposed method with the well-recognized Generative Adversarial Networks (GAN) method. The average peak signal-to-noise ratio (PSNR) and the mean absolute percent error (MAPE) are used for comparison. We also use scoring from three experienced radiologists as subjective measurement means based on the diagnostic consistency of the PET images reconstructed from GAN and the proposed method with respect to the ground truth images. The experiments show that the average PSNR is 47.04dB (the proposed method) vs. 44.41dB (the traditional GAN method) for the reconstructed delayed PET images in our evaluation dataset. The average MAPEs are 1.59% for the proposed method and 3.32% for the traditional GAN method across five organ regions of interest (ROIs). The scores for the GAN and the proposed method rated by three experienced radiologists are 8.08±0.60 and 9.02±0.52, indicating that the proposed method yields more consistent PET images with the ground truth. This work proposes a novel method for CT-less delayed PET imaging based on image synthesis network and nonrigid image registration. The PET image reconstructed using the proposed method yields delayed PET images with high image quality without artifacts and is quantitatively more accurate than the traditional GAN method.

Potential Cardiac Amyloid PET/CT Imaging Targets for Differentiating Immunoglobulin Light Chain From Transthyretin Amyloidosis.

Cardiac involvement in amyloidosis plays a critical role in the clinical manifestation and prognostication. Since advanced treatment options for immunoglobulin light chains (AL) or liver-generated protein transthyretin (TTR) are quite different, a non-invasive and comprehensive imaging approach for the identification and characterization of these forms of cardiac amyloidosis is warranted. Various 18Flabeled radiotracers and positron emission tomography (PET) imaging have been appreciated as a as a valid and non-invasive diagnostic approach to identify and quantify disease activity of cardiac amyloidosis. Interestingly, applying 18F-florbetapen and delayed PET imaging may even afford the possibility to not only detect cardiac amyloidosis but also to reliably differentiate between AL and TTR, respectively. This review summarizes contributions of cardiac PET imaging for the non-invasive identification and potential differentiation between AL and TTR amyloidosis that likely holds promise to gear medical treatment in the individual patient for an improved outcome.

Zero-Extra-Dose PET Delayed Imaging with Data-Driven Attenuation Correction Estimation.

Delayed positron emission tomography (PET) imaging may improve sensitivity and specificity in lesion detection. We proposed a PET data-driven method to estimate the attenuation map (AM) for the delayed scan without an additional x-ray computed tomography (CT). An emission-attenuation-scatter joint estimation framework was developed. Several practical issues for clinical datasets were addressed. Particularly, the unknown scatter correction was incorporated in the joint estimation algorithm. The scaling problem was solved using prior information from the early CT scan. Fourteen patient datasets were added to evaluate the method. These patients went through two separate PET/CT scans. The delayed CT-based AM served as ground truth for the delayed scan. Standard uptake values (SUVmean and SUVmax) of lesion and normal tissue regions of interests (ROIs) in the early and delayed phase and the respective %DSUV (percentage change of SUVmean at two different time points) were analyzed, all with estimated and the true AM. Three radiologists participated in lesion detection tasks with images reconstructed with both AMs and rated scores for detectability. The mean relative difference of SUVmean in lesion and normal liver tissue were 3.30 and 6.69%. The average lesion-to-background contrast (detectability) with delayed PET images using CT AM was 60% higher than that of the earlier PET image, and was 64% higher when using the data-based AM. %DSUV for lesions and liver backgrounds with CT-based AM were - 0.058 ± 0.25 and - 0.33 ± 0.08 while with data-based AM were - 0.00 ± 0.26 and - 0.28 ± 0.08. Only slight significance difference was found between using CT-based AM and using the data-based AM reconstruction delay phase on %DSUV of lesion. The scores associated with the two AMs matched well consistently. Our method may be used in delayed PET imaging, which allows no secondary CT radiation in delayed phase. The quantitative analysis for lesion detection purpose could be ensured.

Monitoring Therapy with MEK Inhibitor U0126 in a Novel Wilms Tumor Model in Wt1 Knockout Igf2 Transgenic Mice Using 18F-FDG PET with Dual-Contrast Enhanced CT and MRI: Early Metabolic Response Without Inhibition of Tumor Growth

PurposeThe understanding of the role of genetic alterations in Wilms tumor development could be greatly advanced using a genetically engineered mouse models that can replicate the development and progression of this disease in human patients and can be monitored using non-invasive structural and molecular imaging optimized for renal tumors.ProceduresRepetitive dual-contrast computed tomography (CT; intravenous and intraperitoneal contrast), T2-weighted magnetic resonance imaging (MRI), and delayed 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) positron emission tomography (PET) were utilized for characterization of Igf2 biallelic expression/Wt1 knockout mouse model of Wilms tumor. For CT imaging, Ioversol 678 mg/ml in 200 μl was administered i.p. followed by 100 μl injected intravenously at 20 and 15 min prior to imaging, respectively. Static PET imaging studies were acquired at 1, 2, and 3 h after i.v. administration of 18F-FDG (400 μCi). Coronal and sagittal T1-weighted images (TE/TR 8.5/620 ms) were acquired before and immediately after i.v. injection of 0.4 ml/kg gadopentetate dimeglumine followed by T2-weighted images (TE/TR 60/300 ms). Tumor tissue samples were characterized by histopathology and immunohistochemistry for Glut1, FASN, Ki67, and CD34. In addition, six Wt1-Igf2 mice were treated with a mitogen-activated protein kinase (MEK) inhibitor U0126 (50 μmol/kg i.p.) every 4 days for 6 weeks. 18F-FDG PET/CT imaging was repeated at different days after initiation of therapy with U0126. The percent change of initial tumor volume and SUV was compared to non-treated historic control animals.ResultsOverall, the best tumor-to-adjacent kidney contrast as well as soft tissue contrast for other abdominal organs was achieved using T2-weighted MRI. Delayed 18F-FDG PET (3-h post 18F-FDG administration) and dual-contrast CT (intravenous and intraperitoneal contrast) provided a more accurate anatomic and metabolic characterization of Wilms tumors in Wt1-Igf2 mice during early development and progression of renal tumors. Over the 8-month period, 46 Wt1-Igf2 mice and 8 littermate control mice were studied. Renal tumors were identified in 54.3 % of Wt1-Igf2 mice between post-natal 50–100 days. In 35.6 % of Wt1-Igf2 mice, tumors were localized in the right kidney; in 24 %, in the left kidney, while 40.4 % of Wt1-Igf2 mice had bilateral kidney tumors. Metastatic lesions were identified in 15.4 % of Wt1-Igf2 mice. Increased levels of Glut1 and IGF1R expression, high Ki67 labeling index, and a dense network of CD34+ microvessels in renal tumors was consistent with increased 18F-FDG accumulation. Treatment with a MEK 1/2 inhibitor U0126 did not cause the inhibition of tumor growth as compared to untreated animals. However, after the first three to four doses (~2 weeks of treatment), a decrease in 18F-FDG SUV was observed, as compared to pre-treatment levels (p < 0.05, paired Student t test), which constitutes a metabolic response. Six weeks later, despite continuing therapy, the 18F-FDG SUV increased again to previous levels.ConclusionsThe optimized dual contrast PET/CT imaging with early post i.v. and i.p. contrast CT and 3 h delayed PET imaging after 18F-FDG administration provides a sensitive and reliable method for detecting early tumor lesions in this endogenous mouse model of Wilms tumor and for monitoring their growth in response to targeted therapies. Therapy with MEK inhibitor U0126 produces only a transient inhibition of tumor glycolytic activity but does not inhibit tumor growth, which is due to continuing IGF2-induced signaling from IGF1R through the PI3K-AKT-mTOR pathway.

RETRACTED ARTICLE: Dual-time point positron emission tomography findings of benign mediastinal lymph nodes in a tuberculosis-endemic region

We performed dual-time-point positron emission tomography imaging (DTPI) in patients without evidence of mediastinal lymph node metastasis to investigate the characteristics of fluorodeoxyglucose (FDG) uptake in benign mediastinal lymph nodes. A total of 118 mediastinal lesions in 24 patients were included in the study. The size, attenuation, maximum standardized uptake value (SUV), and retention indices (RI) were recorded on early and delayed positron emission tomography images for lymph node characterization. The mean SUVs on the early and delayed scans of 118 lymph nodes were 3.3 ± 1.2 and 4.2 ± 1.7, respectively. The mean RI was 26.4% ± 24.5%. Higher FDG uptake was observed in patients with calcified nodules and bilateral FDG uptake and in lymph nodes with calcification or a short-axis diameter >10 mm. In a tuberculosis-endemic area, increments of SUV or RI were frequently observed in benign mediastinal lymph nodes. Therefore, these values, based on mediastinal FDG uptake, might not be accurate indicators of malignant disease.

Fundamentals of PET and PET/CT imaging

In this review, the fundamental principles of fluorodeoxyglucose (FDG) positron emission tomography (PET) and FDG PET/computed tomography (CT) imaging have been described. The basic physics of PET instrumentation, radiotracer chemistry, and the artifacts, as well as normal physiological or benign pathological variants, have been described and presented to the readers in a lucid manner to enable them an easy grasp of the fundamentals of the subject. Finally, we have outlined the current developments in quantitative PET imaging, including dual time point and delayed PET imaging, time-of-flight technology in PET imaging and partial volume correction, and global disease assessment with their potential of being incorporated into the assessment of benign and malignant disorders.

Dual-time-point positron emission tomography findings of benign mediastinal fluorine-18-fluorodeoxyglucose uptake in tuberculosis-endemic region

Background:We performed dual-time-point positron emission tomography imaging in patients without evidences of mediastinal lymph node metastasis to investigate the characteristics of benign mediastinal fluorine-18-fluorodeoxyglucose (FDG) uptake.Materials and Methods:One-hundred and eighteen mediastinal lesions of 24 patients were included for this study. On the early and delayed positron emission tomography images, size, attenuation, maximum standardized uptake value (SUV) and retention indices (RI) were recorded for lymph node characterization.Results:The mean SUV on the early and delayed scan of 118 lymph nodes was 3.3±1.2 and 4.2±1.7, respectively. The mean RI was 26.4±24.5%. Higher FDG uptake was observed in patients with calcified nodules and bilateral FDG uptake and in lymph nodes with calcification or short-axis diameter larger than 10 mm.Conclusion:In tuberculosis-endemic area, the increments of SUV or RI were frequently observed in benign mediastinal lymph nodes, and these values might not be the accurate indicators of malignant disease for mediastinal FDG uptake.

Abstract P5-01-09: Evaluation of Tumor Blood Flow with Dynamic 18F-Fluorodeoxyglucose Positron Emission Tomography: Correlation with Microvessel Density

Abstract Background: Breast cancer is typically associated with an increase in tumor blood flow (due to angiogenesis) and tumor metabolism. Thus, these 2 key parameters are essential to characterize aggressiveness of breast tumors. Moreover, angiogenesis is a potential target for specific therapies. Positron Emission Tomography (PET) with 18F-Fluorodeoxyglucose (FDG) has become the gold standard for in vivo evaluation of tumor metabolism. A method for simultaneous measurement of blood flow and metabolism from a single injection of FDG may be an important addition for functional imaging of breast tumors. Unfortunately, there is no consensus on the validity of dynamic FDG acquisition for the evaluation of tumor blood flow. Objective: to compare a new technique for simultaneous evaluation of tumor blood flow and metabolism, using a dynamic acquisition of FDG PET, with proliferation and endothelial cell markers. Material and methods: Twenty-eight patients with new diagnosed locally advanced breast cancer were included. In addition to diagnosis and tumor grading, biopsy samples of each tumor were used to assess the Ki-67 index of proliferation and the immuno-staining for CD31 (a panendothelial cell marker) and CD105 (a proliferation-related endothelial cell marker) (both expressed as number of labeled vessels counted on 10 consecutive high power fields, 400X magnification). All patients underwent FDG PET at least one week after sample biopsy and before any treatment. Dynamic 2 minutes acquisition was performed immediately after intravenous injection of 5 MBq/Kg of FDG; tumor Blood Flow (BF, in ml/min/g) was then calculated using a single compartiment kinetic model. Static acquisition was performed 60 minutes after injection for quantification of delayed FDG tumor uptake (“Standardized Uptake Value”, SUV), reflecting tumor metabolism. Results: Pathologic and PET data were available for all patients. The SUV measured on delayed PET images was strongly positively correlated with the expression of Ki-67 (r=+0.693; P&amp;lt;0.0001). In contrast, there was no significant correlation between SUV and endothelial markers (CD31 and CD105). Tumor BF was positively correlated with the expression of CD31 (r=+0.392; p=0.039) and CD105 (r=+0.470; p=0.016). In contrast, there was no significant correlation between BF and Ki-67. Patients were categorized according to low (inframedian) or high (supramedian) tumor BF. Patients with high tumor BF showed a higher mean CD31 expression (236±169 vs 124±47, p=0.025) and a higher mean CD105 expression (110±73 vs 51±14; p=0.006) when compared with low tumor BF. In contrast there was no significant difference concerning SUV and Ki-67. Conclusion: Tumor BF quantified by dynamic FDG PET is related to tumor microvessel density evaluated by immunohistochemistry. Thus, dynamic FDG PET is a valuable tool to evaluate both tumor blood flow and metabolism. Further investigations are needed to confirm the respective role of these 2 key parameters for elaboration of therapeutic strategies and response assessment in locally advanced breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-09.

FDG-PET and stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer

To investigate the utility of positron emission tomography (PET) in patients treated with stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) on prospective institutional trials. Fifty-eight patients with medically inoperable stage I NSCLC who participated in prospective phase I and II trials of SBRT, had >or=2 years of follow-up, and received FDG-PET imaging are the focus of this evaluation. Fifty-seven of 58 patients received pre-SBRT FDG-PET to confirm stage I status. All patients received stereotactic body frame immobilization and treatment with 7-10 photon beams. SBRT total doses ranged from 24 to 72Gy in three fractions. No elective nodal irradiation was undertaken. Regular follow-up with planned CT imaging was performed on all patients. Post-SBRT FDG-PET was not mandated by protocol and was typically ordered upon concern for disease recurrence. Thirty-eight post-SBRT PET studies were performed in 28 patients at a median 17.3 months following SBRT. With a median follow-up of 42.5 months, the 3-year actuarial overall survival and local control for this select subset of our SBRT experience were 48.9% and 74.8%, respectively. Pre-SBRT FDG-PET SUV did not predict 3-year overall survival or local control. Fourteen of 57 patients eventually failed in nodal stations by CT and/or PET. Isolated first site of failure was nodal in 6 patients (10%). Out of 28 patients with post-SBRT PET, 4 (14%) had delayed PET imaging (22-26 months after SBRT) showing moderate hypermetabolic activity (SUV 2.5-5.07), but no evidence of local, nodal, or distant recurrence by clinical examination and conventional imaging performed 20-26 months following these concerning PET findings. Isolated nodal recurrence following PET-staged I NSCLC treated with SBRT is uncommon. Moderate post-SBRT PET hypermetabolic activity may persist 2 years following treatment without definite evidence of recurrence. Further study is needed to confirm these results in larger populations with longer follow-up.