Comparative analysis of peri-nidal cerebral blood flow and metabolism using a novel quantitative 15O-PET method in patients with arteriovenous malformations.

To effectively treat cerebral arteriovenous malformations (AVMs), peri-nidal flow regulation and metabolic status must be understood. In this study, we used 15O-oxygen positron emission tomography (PET) post-processing analysis to investigate vascular radioactivity in the nidal region of AVMs. Single-dynamic PET imaging was performed on seven unruptured AVM patients during the sequential inhalation of 15O2 and C15O2. A previously validated dual-tracer basis function method (DBFM) was employed to calculate parametric images. The results of our study were as follows. First, in remote and contralateral AVM regions, DBFM and a previous approach of dual-tracer autoradiography (DARG) showed strong positive correlations in cerebral blood flow (CBF), cerebral oxygen metabolism rate (CMRO2), and oxygen extraction fraction. Second, peri-nidal CBF and CMRO2 correlation was lower, and overestimation occurred with DARG compared to with DBFM. Third, on comparing DBFM to quantitative 123I-iodoamphetamine single-photon emission computed tomography (SPECT), CBF correlated significantly. In contrast, the correlation between DARG and quantitative 123I-iodoamphetamine-SPECT was weaker in the peri-nidal regions. Fourth, analysis of tissue time-activity curves demonstrated good reproducibility using the novel formulation in the control, peri-nidus, and core nidal regions, indicating the adequacy of this approach. Overall, the DBFM approach holds promise for assessing haemodynamic alterations in patients with AVMs.

Dual-Tracer Positron Emission Tomography/Computed Tomography with [18F]FDG and [18F]fluorocholine in a Patient with Metastatic Parathyroid Carcinoma.

Here, we describe the case of a 43-year-old male patient with a metastatic parathyroid carcinoma who underwent dual-tracer whole-body positron emission tomography/computed tomography (PET/CT) with [18F]fluorocholine and fluorodeoxyglucose ([18F]FDG) for staging. [18F]FDG PET/CT detected multiple cervical and mediastinal lymph nodal lesions with increased tracer uptake, whereas [18F]fluorocholine PET/CT detected increased tracer uptake on cervical and mediastinal lymph nodal lesions and bone and lung lesions with a better evaluation of metastatic spread. Due to these imaging findings, the patient underwent systemic treatment with chemotherapy. This case demonstrates the added value of dual-tracer PET/CT in this rare metastatic tumor.

Signal separation of simultaneous dual-tracer PET imaging based on global spatial information and channel attention.

BACKGROUND: Simultaneous dual-tracer positron emission tomography (PET) imaging efficiently provides more complete information for disease diagnosis. The signal separation has long been a challenge of dual-tracer PET imaging. To predict the single-tracer images, we proposed a separation network based on global spatial information and channel attention, and connected it to FBP-Net to form the FBPnet-Sep model. RESULTS: Experiments using simulated dynamic PET data were conducted to: (1) compare the proposed FBPnet-Sep model to Sep-FBPnet model and currently existing Multi-task CNN, (2) verify the effectiveness of modules incorporated in FBPnet-Sep model, (3) investigate the generalization of FBPnet-Sep model to low-dose data, and (4) investigate the application of FBPnet-Sep model to multiple tracer combinations with decay corrections. Compared to the Sep-FBPnet model and Multi-task CNN, the FBPnet-Sep model reconstructed single-tracer images with higher structural similarity, peak signal-to-noise ratio and lower mean squared error, and reconstructed time-activity curves with lower bias and variation in most regions. Excluding the Inception or channel attention module resulted in degraded image qualities. The FBPnet-Sep model showed acceptable performance when applied to low-dose data. Additionally, it could deal with multiple tracer combinations. The qualities of predicted images, as well as the accuracy of derived time-activity curves and macro-parameters were slightly improved by incorporating a decay correction module. CONCLUSIONS: The proposed FBPnet-Sep model was considered a potential method for the reconstruction and signal separation of simultaneous dual-tracer PET imaging.

Dual-tracer PET/CT protocol with [18F]FDG and [68Ga]Ga-FAPI-46 outperforms single-tracer PET/CT with [18F]FDG in different cancer types, resulting in larger functional and gross tumor volume.

PURPOSE: Fibroblast activation protein (FAP) detected by positron-emission tomography (PET) using fibroblast activation protein inhibitor (FAPI) appears to be a promising target for cancer imaging, staging, and therapy, providing added value and strength as a complement to [18F]fluorodeoxyglucose (FDG) in cancer imaging. We recently introduced a combined single-session/dual-tracer protocol with [18F]FDG and [68Ga]Ga-FAPI for cancer imaging and staging. Malignant tissue visualization and target-to-background uptake ratios (TBRs) as well as functional tumor volume (FTV) and gross tumor volume (GTV) were assessed in the present study with single-tracer [18F]FDG PET/computed tomography (CT) and with dual-tracer [18F]FDG&[68Ga]Ga-FAPI-46 PET/CT. METHODS: A total of 19 patients with head and neck and gastrointestinal cancers received initial [18F]FDG-PET/CT followed by dual-tracer PET/CT after additional injection of [68Ga]Ga-FAPI-46 during the same medical appointment (on average 13.9 ± 12.3 min after injection of [18F]FDG). Two readers visually compared detection rate of malignant tissue, TBR, FTV, and GTV for tumor and metastatic tissue in single- and dual-tracer PET/CT. RESULTS: The diagnostic performance of dual-tracer compared to single-tracer PET/CT was equal in 13 patients and superior in 6 patients. The mean TBRs of tumors and metastases in dual-tracer PET/CTs were mostly higher compared to single-tracer PET/CT using maximal count rates (CRmax). GTV and FTV were significantly larger when measured on dual-tracer compared to single-tracer PET/CT. CONCLUSION: Dual-tracer PET/CT with [18F]FDG and [68Ga]Ga-FAPI-46 showed better visualization due to a generally higher TBR and larger FTV and GTV compared to [18F]FDG-PET/CT in several tumor entities, suggesting that [68Ga]Ga-FAPI-46 provides added value in pretherapeutic staging.

Comparison of PET/CT-based eligibility according to VISION and TheraP trial criteria in end-stage prostate cancer patients undergoing radioligand therapy.

BACKGROUND: Two randomized clinical trials demonstrated the efficacy of prostate-specific membrane antigen (PSMA) radioligand therapy (PSMA RLT) in metastatic castration-resistant prostate cancer (mCRPC). While the VISION trial used criteria within PSMA PET/CT for inclusion, the TheraP trial used dual tracer imaging including FDG PET/CT. Therefore, we investigated whether the application of the VISION criteria leads to a benefit in overall survival (OS) or progression-free survival (PFS) for men with mCRPC after PSMA RLT. METHODS: Thirty-five men with mCRPC who had received PSMA RLT as a last-line option and who had undergone pretherapeutic imaging with FDG and [68Ga]Ga-PSMA I&T or [18F]PSMA-1007 were studied. Therapeutic eligibility was retrospectively evaluated using the VISION and TheraP study criteria. RESULTS: 26 of 35 (74%) treated patients fulfilled the VISION criteria (= VISION+) and only 17 of 35 (49%) fulfilled the TheraP criteria (= TheraP+). Significantly reduced OS and PFS after PSMA RLT was observed in patients rated VISION- compared to VISION+ (OS: VISION-: 3 vs. VISION+: 12 months, hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.0-9.1, p < 0.01; PFS: VISION-: 1 vs. VISION+: 5 months, HR 2.7, 95% CI 1.0-7.8, p < 0.01). For patients rated TheraP-, no significant difference in OS but in PFS was observed compared to TheraP+ patients (OS: TheraP-: 5.5 vs. TheraP+: 11 months, HR 1.6, 95% CI 0.8-3.3, p = 0.2; PFS: TheraP-: 1 vs. TheraP+: 6 months, HR 2.2, 95% CI 1.0-4.5, p < 0.01). CONCLUSION: Retrospective application of the inclusion criteria of the VISION study leads to a benefit in OS and PFS after PSMA RL, whereas TheraP criteria appear to be too strict in patients with end-stage prostate cancer. Thus, performing PSMA PET/CT including a contrast-enhanced CT as proposed in the VISION trial might be sufficient for treatment eligibility of end-stage prostate cancer patients.

Current and Future Use of Long Axial Field-of-View Positron Emission Tomography/Computed Tomography Scanners in Clinical Oncology.

The latest technical development in the field of positron emission tomography/computed tomography (PET/CT) imaging has been the extension of the PET axial field-of-view. As a result of the increased number of detectors, the long axial field-of-view (LAFOV) PET systems are not only characterized by a larger anatomical coverage but also by a substantially improved sensitivity, compared with conventional short axial field-of-view PET systems. In clinical practice, this innovation has led to the following optimization: (1) improved overall image quality, (2) decreased duration of PET examinations, (3) decreased amount of radioactivity administered to the patient, or (4) a combination of any of the above. In this review, novel applications of LAFOV PET in oncology are highlighted and future directions are discussed.

A dual-tracer approach using [11C]CH and [18F]FDG in HCC clinical decision making.

BACKGROUND: Early detection of recurrent or progressive HCC remains the strongest prognostic factor for survival. Dual tracer PET/CT imaging with [11C]CH and [18F]FDG can further increase detection rates as both tracers entail different metabolic pathways involved in HCC development. We investigated dual-tracer PET/CT in clinical decision making in patients suspected of recurrent or progressive HCC. All HCC patients who underwent both [11C]CH and [18F]FDG PET/CT in our institute from February 2018 to December 2021 were included. Both tracer PET/CT were within 4 weeks of each other with at least 6-month follow-up. Patients underwent dual tracer PET/CT because of unexplained and suspicious CT/MRI or sudden rise of serum tumour markers. A detected lesion was considered critical when the finding had prognostic consequences leading to treatment changes. RESULTS: Nineteen patients who underwent [11C]CH and [18F]FDG PET/CT were included of which all but six patients were previously treated for HCC. Dual-tracer critical finding detection rate was 95%, with [18F]FDG 68%, and [11C]CH 84%. Intrahepatic HCC recurrence finding rate was 65% for both tracers. [18F]FDG found more ablation site recurrences (4/5) compared to [11C]CH (2/5). Only [11C]CH found two needle tract metastases. Both tracers found 75% of the positive lymph nodes. Two new primary tumours were found, one by [18F]FDG and both by [11C]CH. CONCLUSIONS: Our study favours a dual-tracer approach in HCC staging in high-risk patients or when conventional imaging is non-conclusive.

Differentiation of Discordant Lesions on Dual-Tracer PET/CT (68Ga-PSMA-11 and 18F-FDG) in Prostate Carcinoma: Diagnosis of Second Primary Malignancies.

We present 2 cases of metastatic castration-resistant prostate carcinoma with discordant lesions on dual-tracer PET/CT (68Ga-PSMA-11 and 18F-FDG PET/CT), which on subsequent histopathologic evaluation revealed second primary malignancies of combined hepatocellular carcinoma and cholangiocarcinoma and poorly differentiated squamous cell carcinoma. These case illustrations emphasize the need to evaluate discordant lesions on dual-tracer PET/CT, which can lead to early diagnosis of second primary malignancies and thereby can provide better management in these patients.

Dual-Tracer Parathyroid Imaging Using Joint SPECT Reconstruction.

Purpose: We assessed the lesion detection performance of the dual-tracer parathyroid SPECT imaging using the joint reconstruction method. Materials and Methods: Thirty-six noise realizations were created from SPECT projections collected from an in-house neck phantom to emulate 99mTc-pertechnetate/99mTc-sestamibi parathyroid SPECT datasets. Difference images representing parathyroid lesions were reconstructed using the subtraction and the joint methods whose corresponding optimal iteration was defined as the iteration which maximized the channelized Hotelling observer signal-to-noise ratio (CHO-SNR). The joint method whose initial estimate was derived from the subtraction method at optimal iteration (the joint-AltInt method) was also assessed. In a study of 36 patients, a human-observer lesion-detection study was performed using difference images from the three methods at optimal iteration and the subtraction method with four iterations. The area under the receiver operating characteristic curve (AUC) was calculated for each method. Results: In the phantom study, both the joint-AltInt method and the joint method improved SNR compared to the subtraction method at their optimal iteration by 444% and 81%, respectively. In the patient study, the joint-AltInt method yielded the highest AUC of 0.73 as compared with 0.72, 0.71, and 0.64 from the joint method, the subtraction method at optimal iteration, and the subtraction method at four iterations. At a specificity of at least 0.70, the joint-AltInt method yielded significantly higher sensitivity than the other methods (0.60 vs 0.46, 042, and 0.42; p < 0.05). Conclusions: The joint reconstruction method yielded higher lesion detectability than the conventional method and holds promise for dual-tracer parathyroid SPECT imaging.

Indispensable Amino Acid Digestibility of Moroccan Fava Bean Using the Dual Isotope Method in Healthy Adults.

BACKGROUND: Assessment of protein quality is necessary to satisfy the nutritional needs of populations across the world. In addition to indispensable amino acid (IAAs) composition, protein digestibility is a major component of IAA bioavailability, playing a crucial role in human health and affecting the linear growth of children. OBJECTIVES: This study aimed to evaluate IAA digestibility of fava beans, a legume widely consumed in Morocco using the dual-tracer method. METHODS: 2H-intrinsically labeled Fava beans supplemented with 12 mg/kg BW of 13C spirulina were given to 5 healthy volunteers (3 men and 2 women), aged 25.8 ± 3.3 y, with a mean BMI of 20.0 kg/m2. The meal was spread in small portions and was given hourly throughout 7 h. Blood was sampled at baseline and hourly from 5 to 8 h after meal ingestion. IAA digestibility was evaluated by gas chromatography-combustion-isotope ratio mass spectrometry using the 2H/13C ratio in plasma IAA. Digestible indispensable amino acid ratios (DIAAR) were calculated using the scoring pattern for people older than 3 y. RESULTS: Fava beans had an adequate level of lysine but were limiting in several IAAs, especially methionine. Under our experimental conditions, the average IAA digestibility of fava bean was 61.1% ± 5.2%. Valine had the highest digestibility (68.9% ± 4.3%) and threonine had the lowest (43.7% ± 8.2%). In consequence, the lowest DIAAR was 67% for threonine and only 47% for sulfur amino acids (SAA). CONCLUSIONS: The present study is the first to determine the digestibility of fava bean amino acids in humans. The mean IAA digestibility was moderate, and consequently, we conclude that fava bean provides a limited amount of several IAAs, especially SAA, but adequately for lysine. Preparation and cooking methods of fava beans should be improved to increase digestibility. This study was registered at ClinicalTrials.gov as NCT04866927.

One-stop [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 total-body PET/CT examination with dual-low activity: a feasibility study.

PURPOSE: Positron emission tomography/computed tomography (PET/CT) based on fibroblast activation protein inhibitors (FAPI) has shown complementary values to 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) in cancer imaging. This study aimed to investigate the feasibility of a one-stop FDG-FAPI dual-tracer imaging protocol with dual-low activity for oncological imaging. METHODS: Nineteen patients with malignancies underwent one-stop [18F]FDG (0.37 MBq/kg) PET (PETFDG) and dual-tracer PET 30-40 and 50-60 min (hereafter, PETD30-40 and PETD50-60, respectively) after additional injection of [68Ga]Ga-DOTA-FAPI-04 (0.925 MBq/kg), with a single diagnostic CT to generate the PET/CT. The lesion detection rate and tumor-to-normal ratios (TNRs) of tracer uptake were compared between PETFDG/CT and PETD50-60/CT and between PETD50-60/CT and PETD30-40/CT. In addition, a visual scoring system was established to compare the lesion detectability. RESULTS: The dual-tracer PETD50-60 and PETD30-40/CT showed similar performance in detecting primary tumors but presented significantly higher lesion TNRs than PETFDG. Significantly, more metastases with higher TNRs were identified on PETD50-60 than PETFDG (491 vs. 261, P < 0.001). The dual-tracer PETD50-60 received significantly higher visual scores than single PETFDG (111 vs. 10) in demonstrating both primary tumors (12 vs. 2) and metastases (99 vs. 8). However, these differences were not significant between PETD50-60 and PETD30-40. These resulted in tumor upstaging in 44.4% patients taking PET/CT for initial assessment, and more recurrences (68 vs. 7) were identified in patients taking PET/CT for restaging, both on PETD50-60 and PETD30-40, compared to PETFDG. The reduced effective dosimetry per patient (26.2 ± 2.57 mSv) was equal to that of a single standard whole-body PET/CT. CONCLUSION: The one-stop dual-tracer dual-low-activity PET imaging protocol combines the strengths of [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 with shorter duration and lesser radiation and is thus clinically applicable.

Design of a generic method for single dual-tracer PET imaging acquisition in clinical routine.

Using different tracers in positron emission tomography (PET) imaging can bring complementary information on tumor heterogeneities. Ideally, PET images of different tracers should be acquired simultaneously to avoid the bias induced by movement and physiological changes between sequential acquisitions. Previous studies have demonstrated the feasibility of recovering separated PET signals or parameters of two or more tracers injected (quasi-)simultaneously in a single acquisition. In this study, a generic framework in the context of dual-tracer PET acquisition is proposed where no strong kinetic assumptions nor specific tuning of parameters are required. The performances of the framework were assessed through simulations involving the combination of [18F]FCH and [18F]FDG injections, two protocols (90 and 60 min acquisition durations) and various activity ratios between the two injections. Preclinical experiments with the same radiotracers were also conducted. Results demonstrate the ability of the method both to extract separated arterial input functions (AIF) from noisy image-derived input function and to separate the dynamic signals and further estimate kinetic parameters. The compromise between bias and variance associated with the estimation of net influx rateKishows that it is preferable to use the second injected radiotracer with twice the activity of the first for both 90 min [18F]FCH+[18F]FDG and 60 min [18F]FDG+[18F]FCH protocols. In these optimal settings, the weighted mean-squared-error of the estimated AIF was always less than 7%. TheKibias was similar to the one of single-tracer acquisitions; below 5%. Compared to single-tracer results, the variance ofKiwas twice more for 90 min dual-tracer scenario and four times more for the 60 min scenario. The generic design of the method makes it easy to use for other pairs of radiotracers and even for more than two tracers. The absence of strong kinetic assumptions and tuning parameters makes it suitable for a possible use in clinical routine.

Dual-Tracer PET-MRI-Derived Imaging Biomarkers for Prediction of Clinically Significant Prostate Cancer.

PURPOSE: To investigate if imaging biomarkers derived from 3-Tesla dual-tracer [(18)F]fluoromethylcholine (FMC) and [68Ga]Ga-PSMAHBED-CC conjugate 11 (PSMA)-positron emission tomography can adequately predict clinically significant prostate cancer (csPC). METHODS: We assessed 77 biopsy-proven PC patients who underwent 3T dual-tracer PET/mpMRI followed by radical prostatectomy (RP) between 2014 and 2017. We performed a retrospective lesion-based analysis of all cancer foci and compared it to whole-mount histopathology of the RP specimen. The primary aim was to investigate the pretherapeutic role of the imaging biomarkers FMC- and PSMA-maximum standardized uptake values (SUVmax) for the prediction of csPC and to compare it to the mpMRI-methods and PI-RADS score. RESULTS: Overall, we identified 104 cancer foci, 69 were clinically significant (66.3%) and 35 were clinically insignificant (33.7%). We found that the combined FMC+PSMA SUVmax were the only significant parameters (p < 0.001 and p = 0.049) for the prediction of csPC. ROC analysis showed an AUC for the prediction of csPC of 0.695 for PI-RADS scoring (95% CI 0.591 to 0.786), 0.792 for FMC SUVmax (95% CI 0.696 to 0.869), 0.852 for FMC+PSMA SUVmax (95% CI 0.764 to 0.917), and 0.852 for the multivariable CHAID model (95% CI 0.763 to 0.916). Comparing the AUCs, we found that FMC+PSMA SUVmax and the multivariable model were significantly more accurate for the prediction of csPC compared to PI-RADS scoring (p = 0.0123, p = 0.0253, respectively). CONCLUSIONS: Combined FMC+PSMA SUVmax seems to be a reliable parameter for the prediction of csPC and might overcome the limitations of PI-RADS scoring. Further prospective studies are necessary to confirm these promising preliminary results.

Direct reconstruction for simultaneous dual-tracer PET imaging based on multi-task learning.

BACKGROUND: Simultaneous dual-tracer positron emission tomography (PET) imaging can observe two molecular targets in a single scan, which is conducive to disease diagnosis and tracking. Since the signals emitted by different tracers are the same, it is crucial to separate each single tracer from the mixed signals. The current study proposed a novel deep learning-based method to reconstruct single-tracer activity distributions from the dual-tracer sinogram. METHODS: We proposed the Multi-task CNN, a three-dimensional convolutional neural network (CNN) based on a framework of multi-task learning. One common encoder extracted features from the dual-tracer dynamic sinogram, followed by two distinct and parallel decoders which reconstructed the single-tracer dynamic images of two tracers separately. The model was evaluated by mean squared error (MSE), multiscale structural similarity (MS-SSIM) index and peak signal-to-noise ratio (PSNR) on simulated data and real animal data, and compared to the filtered back-projection method based on deep learning (FBP-CNN). RESULTS: In the simulation experiments, the Multi-task CNN reconstructed single-tracer images with lower MSE, higher MS-SSIM and PSNR than FBP-CNN, and was more robust to the changes in individual difference, tracer combination and scanning protocol. In the experiment of rats with an orthotopic xenograft glioma model, the Multi-task CNN reconstructions also showed higher qualities than FBP-CNN reconstructions. CONCLUSIONS: The proposed Multi-task CNN could effectively reconstruct the dynamic activity images of two single tracers from the dual-tracer dynamic sinogram, which was potential in the direct reconstruction for real simultaneous dual-tracer PET imaging data in future.

The Complementary Role of PET to Pathology in Differentiating the Primary Origin of a Malignant Skin Nodule from Liver or Lung.

Metastasis from unknown primary is always a challenge because finding the true primary tumor significantly affects subsequent management. We present a case of malignant abdominal wall nodule initially diagnosed as metastasis from hepatocellular carcinoma through excisional biopsy and immunohistochemical (IHC) staining. Dual-tracer positron emission tomography/computed tomography (PET/CT) with 11C-acetate and 18F-FDG, however, showed metabolic findings in favor of metastasis from lung origin, which was finally confirmed by ensuing a lung biopsy with additional IHC stains. This case illustrates the complementary molecular role of PET to pathology, particularly when dual-tracer or multi-tracer PET is used in conjunction with pathology methods for cross referencing and confirmation.

Metachronous Adenocarcinoma of the Lung in the Setting of Metastatic Gastric Neuroendocrine Tumor: Value of Elucidating Discordance on Dual-Tracer PET/CT with Ki-67 Index.

Dual-tracer PET/CT (18F-FDG and 68Ga-DOTATATE) has become established practice in the management of metastatic neuroendocrine neoplasms (NENs) and has demonstrated the advantages to patient management of deciphering the molecular PET characteristics of the tumor. Judicious elucidation of the findings is important, especially in scenarios of discordance with reported histopathology, potentially leading to an unsuspected diagnosis such as second primary malignancies. Such a diagnosis established early in the disease course, and mostly at an asymptomatic stage, provides lead time for timely, appropriate management. This concept was elaborated in a case of incidentally detected 18F-FDG-avid metachronous lung adenocarcinoma in a patient with metastatic, well-differentiated gastric NEN, wherein dual-tracer PET/CT showed 18F-FDG-avid but not 68Ga-DOTATATE-avid lung opacity.

Dual-Tracer PET-Computed Tomography Imaging for Precision Radio-Molecular Theranostics of Prostate Cancer: A Futuristic Perspective.

Dual/multi-tracer PET-computed tomography (CT) scan has been an interesting and intriguing concept and is promising in noninvasive and overall characterization of tumor biology and heterogeneity and has scientifically augmented the practice of precision oncology. In prostate carcinoma, particularly in metastatic castration-resistant prostate carcinoma setting, dual-tracer PET-CT can be potentially useful in selecting patients for chemotherapy, androgen deprivation therapy or prostate-specific membrane antigen (PSMA)-based peptide receptor radioligand therapy either as mono-therapy or as combination therapy, ascertaining differentiation status, staging/restaging, prognostication, and predicting progression/response. PSMA PET/CT has great potential as a "rule out" test in baseline staging, while being very useful in restaging and metastatic workup.

Dual-Tracer PET/CT Protocol with [18F]-FDG and [68Ga]Ga-FAPI-46 for Cancer Imaging: A Proof of Concept.

Imaging studies with PET tracers acting as fibroblast activation protein inhibitors (FAPIs) show promising results that could usefully complement [18F]-FDG in cancer imaging. Methods: All patients received [18F]-FDG PET/CT and dual-tracer PET/CT after an additional injection of [68Ga]Ga-FAPI-46 after the [18F]-FDG PET/CT. Two readers visually compared detection rate and analyzed target-to-background ratios for tumor and metastatic tissue in single- and dual-tracer PET/CT. Results: Detection rate in dual-tracer PET/CT was visually as good as that in single-tracer PET/CT in 4 patients and superior in 2 patients, whereas target-to-background ratios were significantly higher in dual-tracer PET/CT. Conclusion: Dual-tracer [18F]-FDG/[68Ga]Ga-FAPI-46 PET/CT within a single session is feasible and has potential. The dual-tracer approach may have superior sensitivity to [18F]-FDG PET/CT alone without compromising individual assessment of either scan.

Temporal information-guided dynamic dual-tracer PET signal separation network.

PURPOSE: The difficulty of dynamic dual-tracer positron emission tomography (PET) technology is to separate the complete single-tracer information from mixed dual-tracer. Traditional methods cannot separate single-injection single-scan dynamic dual-tracer PET images. In this paper, we propose a deep learning framework based on gated recurrent unit (GRU) network and evaluate its performance with simulation experiments and realistic monkey data. METHODS: The proposed single-scan dynamic dual-tracer PET image separation network consists of three parts, including encoder, separation, and decoder module. Encoder part is to map the mixed time activity curves (TACs) from the low-dimensional space to the high-dimensional space to get mixed weight vector matrix. Separation part is to capture the temporal information of mixed weight vector matrix using bi-directional GRU (bi-GRU) layer to obtain the single-tracer masks, and the decoding part remaps the high-dimensional single-tracer weight vector matrix to the low-dimensional space to obtain two separated single tracers. RESULTS: In the simulation experiments under different tracers, phantoms, noise levels, arterial input function (AIF), and k-parameter with Gaussian random, compared to the stacked auto encoder network and traditional background subtraction method, GRU-based network has better performance with low bias and mean squared error. In the realistic study, the image results of GRU network have higher mean structural similarity and peak signal to noise ratio. CONCLUSIONS: This study demonstrates the feasibility of temporal information-guided neural network in single-injection single-scan dynamic dual-tracer PET images separation. The GRU-based network uses TAC temporal information without AIFs to make the separation results more robust and accurate, which significantly outperforms state-of-the-art method qualitatively and quantitatively.

Discordance Between Histopathologic Grading and Dual-Tracer PET/CT Findings in Metastatic NETs and Outcome of 177Lu-DOTATATE PRRT: Does In Vivo Molecular PET Perform Better from the Viewpoint of Prediction of Tumor Biology?

Discordance between histopathologic grading and dual-tracer PET/CT (68Ga-DOTATATE and 18F-FDG) findings in neuroendocrine tumors (NETs), though not typical, can be encountered in real-world scenarios. The aim of this study was to assess patients with discordance between World Health Organization (WHO) 2017 grade-predicted molecular PET/CT imaging and the actual dual-tracer PET/CT findings (by exploring their histopathologic, immunohistochemical, and molecular imaging characteristics), with a view toward identifying the prognostic determinants affecting outcome in a peptide receptor radionuclide therapy setup. Methods: Thirty-six patients with histopathologically proven inoperable, locally advanced or metastatic NETs, referred for peptide receptor radionuclide therapy, were included in this study. The cohort was divided into 2 broad population groups: those with discordance (between WHO 2017 grade-predicted molecular imaging and the dual-tracer PET/CT findings) and control (showing both 18F-FDG and 68Ga-DOTATATE uptake). The cohort was divided on the basis of dual-tracer PET/CT into 3 groups: metabolically inactive (non-18F-FDG-avid) and somatostatin receptor (SSTR)-expressing tumors, metabolically active (18F-FDG-avid) and non-68Ga-DOTATATE-concentrating (non-SSTR-expressing) tumors, and matched imaging characteristics with the WHO 2017 grading system (showing both 18F-FDG- and 68Ga-DOTATATE-concentrating disease) for statistical analysis. Descriptive statistics were used to analyze categoric data; multivariate analysis was used to assess the correlation between different variables with progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves were used for survival analysis to calculate median survival and to analyze survival on the basis of WHO 2017 grading and dual-tracer PET. Cox proportional hazards regression analysis was used to determine predictors of survival (OS and PFS). Results: Of the 36-patient cohort, 24 (66.7%) showed discordance and 12 (33.3%) were in the control group. Among those showing discordance: 14 (38.9%) had metabolically inactive and SSTR-expressing disease and the remaining 10 (27.8%) had 18F-FDG-concentrating and non-SSTR-expressing disease. Among those in the control group, 12 (33.3%) had intermediate-grade NETs and showed matched (68Ga-DOTATATE- and 18F-FDG-concentrating lesions) disease. Multivariate analysis in patients with discordant findings showed a significant correlation of dual-tracer PET with OS, whereas no significant correlation could be established between WHO grade and OS in the discordant subgroups. No significant correlation could be appreciated between PFS and either dual-tracer PET or WHO grading. The Kaplan-Meier analysis and Cox analysis showed dual-tracer PET/CT imaging to be a significant prognostic determinant and predictor of outcome, respectively. Conclusion: In NET patients with discordance between the 2 parameters, dual-tracer PET/CT with 18F-FDG and 68Ga-DOTATATE performed better than WHO grading, differentiation status, and immunohistochemistry in prognosticating and predicting outcome.