[18F]DCFPyL PET/CT versus [18F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study.

PURPOSE: Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.

Evaluation of a convolution neural network for baseline total tumor metabolic volume on [18F]FDG PET in diffuse large B cell lymphoma.

OBJECTIVES: New PET data-processing tools allow for automatic lesion selection and segmentation by a convolution neural network using artificial intelligence (AI) to obtain total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) routinely at the clinical workstation. Our objective was to evaluate an AI implemented in a new version of commercial software to verify reproducibility of results and time savings in a daily workflow. METHODS: Using the software to obtain TMTV and TLG, two nuclear physicians applied five methods to retrospectively analyze data for 51 patients. Methods 1 and 2 were fully automated with exclusion of lesions ≤ 0.5 mL and ≤ 0.1 mL, respectively. Methods 3 and 4 were fully automated with physician review. Method 5 was semi-automated and used as reference. Time and number of clicks to complete the measurement were recorded for each method. Inter-instrument and inter-observer variation was assessed by the intra-class coefficient (ICC) and Bland-Altman plots. RESULTS: Between methods 3 and 5, for the main user, the ICC was 0.99 for TMTV and 1.0 for TLG. Between the two users applying method 3, ICC was 0.97 for TMTV and 0.99 for TLG. Mean processing time (± standard deviation) was 20 s ± 9.0 for method 1, 178 s ± 125.7 for method 3, and 326 s ± 188.6 for method 5 (p < 0.05). CONCLUSION: AI-enabled lesion detection software offers an automated, fast, reliable, and consistently performing tool for obtaining TMTV and TLG in a daily workflow. KEY POINTS: • Our study shows that artificial intelligence lesion detection software is an automated, fast, reliable, and consistently performing tool for obtaining total metabolic tumor volume and total lesion glycolysis in a daily workflow.

Quantitation of myocardial 99mTc-HMDP uptake with new SPECT/CT cadmium zinc telluride (CZT) camera in patients with transthyretin-related cardiac amyloidosis: Ready for clinical use?

BACKGROUND: The aim of this study was to investigate the feasibility of assessing absolute myocardial 99mTc-HMDP uptake in patients with suspected cardiac ATTR using SUV with a whole-body CZT SPECT-CT camera (DNM670CZT). METHODS: Fifteen patients with suspected cardiac ATTR (Perugini ≥ 2) underwent a conventional 99mTc-HMDP planar imaging and a thoracic SPECT/CT using a DNM 670CZT. A control group consisted of 15 patients with negative scintigraphy (Perugini < 2). SUVmax (mg·L-1) and percentage of injected dose (%ID) were calculated in a cardiac volume of interest (VOI) encompassing the left ventricle. VOIs were also placed in the lung, the right pectoris major, and the sternum. A heart-to-lung SUVmax ratio (HLR) was calculated. RESULTS: All ATTR patients demonstrated an increased cardiac HMDP SUVmax (12.2 ± 3.7 mg·L-1) vs controls (3.5 ± 1.2, P < .0001). Percentage of ID, pectoral uptake and HLR were significantly higher in the ATTR group (1.1 ± 0.3 vs 0.15 ± 0.8, P < .0001; 1.5 ± 0.3 vs 0.9 ± 0.3, P < .0001; 9.7 ± 3 vs 4.3 ± 2.2, P < .0001). Bone uptake was not statistically different between the two groups. CONCLUSION: This study demonstrated the feasibility of quantitative 99mTc-HMDP SUVmax measurement using a whole-body SPECT/CT CZT camera in patients with suspected cardiac ATTR.

First Follow-Up of Cardiac Amyloidosis Treated by Tafamidis, Evaluated by Absolute Quantification in Bone Scintigraphy.

Assessment of absolute myocardial hydroxydimethylene diphosphonate-technetium-99m uptake using standardized uptake value with a single-photon emission computed tomography-computed tomography cadmium zinc telluride camera (Discovery NM/CT 670CZT, GE Healthcare, Chicago, Illinois) in a patient with cardiac transthyretin-related amyloidosis treated with tafamidis showed a decrease in hydroxydimethylene diphosphonate cardiac uptake. This imaging technique should be helpful in monitoring therapy and evaluating prognosis. (Level of Difficulty: Intermediate.).

First comparison of performances between the new whole-body cadmium-zinc-telluride SPECT-CT camera and a dedicated cardiac CZT camera for myocardial perfusion imaging: Analysis of phantom and patients.

BACKGROUND: Dedicated cardiac Cadmium-zinc-telluride (CZT) cameras show superior performances compared with Anger systems, particularly in terms of spatial resolution and count sensitivity. This study evaluated the performances of a new polyvalent whole body CZT camera (DNM 670CZT) compared with a cardiac dedicated CZT camera (DNM 530c) for myocardial perfusion SPECT. METHODS: The spatial resolution was evaluated with three linear sources filled with 99mTc. We used a cardiac phantom to evaluate count sensitivity, sharpness index, contrast-to-noise ratio, wall thickness, non-uniformity index, perfusion scores and ventricle volumes for both cameras. The impact of matrix size, and acquisition time was investigated. Concordance between the two cameras was evaluated in patients using QPS/QGS software for quantitative segmental perfusion, motion and thickness scores. RESULTS: The spatial resolution was identical with the two cameras. Count sensitivity of the DNM 670CZT was twofold lower compared with the DNM 530c, leading to lower sharpness index and contrast-to-noise ratio. The wall thickness and the myocardial volumes were similar. Visual and quantitative assessments of the perfusion patterns have shown a good concordance of the two cameras on phantoms and in patients. CONCLUSION: This study demonstrated the feasibility of myocardial perfusion SPECT imaging using the new whole-body DNM 670CZT camera.

Determination of the Heart-to-Mediastinum Ratio of 123I-MIBG Uptake Using Dual-Isotope (123I-MIBG/99mTc-Tetrofosmin) Multipinhole Cadmium-Zinc-Telluride SPECT in Patients with Heart Failure.

The aim of this retrospective study was to compare the heart-to-mediastinum ratio (HMR) of 123I-metaiodobenzylguanidine (123I-MIBG) uptake obtained using a multipinhole cadmium-zinc-telluride (CZT) camera with that obtained using conventional planar imaging. Methods: Forty consecutive heart failure patients underwent planar acquisition 4 h after 123I-MIBG injection (191 ± 41 [mean ± SD] MBq). To localize the heart using the CZT camera, 99mTc-tetrofosmin (358 ± 177 MBq) was administered and dual-isotope acquisition was performed. The HMRs were calculated with conventional planar imaging (HMRplanar), with anterior reprojection images using the CZT camera (HMRreproj), and with transaxial reconstructed images using the CZT camera (HMRtransaxial). In a phantom study, we estimated a linear model fitting the CZT camera data to the planar data, and we applied it to provide corrected CZT camera-determined HMRs in patients (cHMRreproj and cHMRtransaxial). Results: Thirty-four men and 6 women (71 ± 9 y old) with ischemic (22 patients) and nonischemic (18 patients) heart failure completed the study. For 22 of the 40 patients (55%), the New York Heart Association classification was class II and the ejection fraction was 35% ± 9%. HMRreproj (1.12 ± 0.19) and HMRtransaxial (1.35 ± 0.34) were lower than HMRplanar (1.44 ± 0.14) (P < 0.0001 and P < 0.01, respectively). cHMRreproj (1.54 ± 0.09) and cHMRtransaxial (1.45 ± 0.14) were significantly different (P < 0.0001). Lin concordance correlation and Bland-Altman analysis demonstrated an almost perfect concordance and a high agreement between HMRplanar and cHMRtransaxial (P was not significant) but not between HMRplanar and cHMRreproj (P < 0.0001). Conclusion: This study demonstrated that determination of the late HMR of cardiac 123I-MIBG uptake using dual-isotope (123I and 99mTc) acquisition on a multipinhole CZT camera was feasible in patients with heart failure. However, this determination should be performed using transaxial reconstructed images and linear correction based on phantom data acquisitions.

First assessment of simultaneous dual isotope (123I/99mTc) cardiac SPECT on two different CZT cameras: A phantom study.

BACKGROUND: We studied the impact of simultaneous dual-isotope acquisition on 123I/99mTc mismatch assessment using two CZT cameras (DNM 530c, GE Healthcare and DSPECT, Biosensors International). METHODS: We used an anthropomorphic torso phantom (respectively filled with a solution of 123I alone, 99mTc alone, and a mixture of 123I and 99mTc) and its cardiac insert with two defects mimicking two matched and mismatched defects. Mismatch extent and reconstructed image contrast were evaluated. RESULTS: The acquisition mode (single vs dual) significantly impacted (i) 99mTc (but not 123I) reconstructed segmental activities using both camera (P < .001), and (ii) image contrast (using 123I and DNM 530c, P < .0001; and using both 123I and 99mTc with DSPECT, P < .0001). However, the defect and mismatch size were not impacted by the type of acquisition. With both DNM 530c and DSPECT, Lin's concordance correlation coefficient and Bland-Altman analysis demonstrated an almost perfect concordance and agreement between single- and simultaneous dual-isotope segmental activity (123I and 99mTc). CONCLUSIONS: This study found no impact of the acquisition mode (single vs dual) or the type of camera (DSPECT vs DNM 530c) on 123I and 99mTc defect size and mismatch, providing a new step toward simultaneous dual-isotope acquisition for combined innervation and perfusion assessment.

Left ventricular function assessment using 123I/99mTc dual-isotope acquisition with two semi-conductor cadmium-zinc-telluride (CZT) cameras: a gated cardiac phantom study.

BACKGROUND: The impact of increased energy resolution of cadmium-zinc-telluride (CZT) cameras on the assessment of left ventricular function under dual-isotope conditions (99mTc and 123I) remains unknown. The Amsterdam-gated dynamic cardiac phantom (AGATE, Vanderwilt techniques, Boxtel, The Netherlands) was successively filled with a solution of 123I alone, 99mTc alone, and a mixture of 123I and 99mTc. A total of 12 datasets was acquired with each commercially available CZT camera (DNM 530c, GE Healthcare and DSPECT, Biosensors International) using both energy windows (99mTc or 123I) with ejection fraction set to 33, 45, and 60 %. End-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (LVEF), and regional wall motion and thickening (17-segment model) were assessed using Cedars-Sinai QGS Software. Concordance between single- and dual-isotope acquisitions was tested using Lin's concordance correlation coefficient (CCC) and Bland-Altman plots. RESULTS: There was no significant difference between single- or simultaneous dual-isotope acquisition (123I and 99mTc) for EDV, ESV, LVEF, or segmental wall motion and thickening. Myocardial volumes using single- (123I, 99mTc) and dual-isotope (reconstructed using both 123I and 99mTc energy windows) acquisitions were, respectively, the following: EDV (mL) 88 ± 27 vs. 89 ± 27 vs. 92 ± 29 vs. 90 ± 26 for DNM 530c (p = NS) and 82 ± 20 vs. 83 ± 22 vs. 79 ± 19 vs. 77 ± 20 for DSPECT (p = NS); ESV (mL) 40 ± 1 vs. 41 ± 2 vs. 41 ± 2 vs. 42 ± 1 for DNM 530c (p = NS) and 37 ± 5 vs. 37 ± 1 vs. 35 ± 3 vs. 34 ± 2 for DSPECT (p = NS); LVEF (%) 52 ± 14 vs. 51 ± 13 vs. 53 ± 13 vs. 51 ± 13 for DNM 530c (p = NS) and 52 ± 16 vs. 54 ± 13 vs. 54 ± 14 vs. 54 ± 13 for DSPECT (p = NS); regional motion (mm) 6.72 ± 2.82 vs. 6.58 ± 2.52 vs. 6.86 ± 2.99 vs. 6.59 ± 2.76 for DNM 530c (p = NS) and 6.79 ± 3.17 vs. 6.81 ± 2.75 vs. 6.71 ± 2.50 vs. 6.62 ± 2.74 for DSPECT (p = NS). The type of camera significantly impacted only on ESV (p < 0.001). CONCLUSIONS: The new CZT cameras yielded similar results for the assessment of LVEF and regional motion using different energy windows (123I or 99mTc) and acquisition types (single vs. dual). With simultaneous dual-isotope acquisitions, the presence of 123I did not impact on LVEF assessment within the 99mTc energy window for either CZT camera.

Left Ventricular Function Assessment Using 2 Different Cadmium-Zinc-Telluride Cameras Compared with a γ-Camera with Cardiofocal Collimators: Dynamic Cardiac Phantom Study and Clinical Validation.

UNLABELLED: This study compared two SPECT cameras with cadmium-zinc-telluride (CZT) detectors to a conventional Anger camera with cardiofocal collimators for the assessment of left ventricular (LV) function in a phantom and patients. METHODS: A gated dynamic cardiac phantom was used. Eighteen acquisitions were processed on each CZT camera and the conventional camera. The total number of counts within a myocardial volume of interest varied from 0.25 kcts to 1.5 Mcts. Ejection fraction was set to 33%, 45%, or 60%. Volume, LV ejection fraction (LVEF), regional wall thickening, and motion (17-segment model) were assessed. One hundred twenty patients with a low pretest likelihood of coronary artery disease and normal findings on stress perfusion SPECT were retrospectively analyzed to provide the reference limits for end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction, and regional function for each camera model. RESULTS: In the phantom study, for each ejection fraction value, volume was higher for the CZT cameras than for the conventional camera, resulting in a decreased but more accurate LVEF (all P < 0.001). In clinical data, body-surface-indexed EDV and ESV (mL/m(2)) were higher for one of the CZT cameras (Discovery NM 530c) than for the other (D-SPECT) or the conventional camera (respectively, 40.5 ± 9.2, 37 ± 7.9, and 35.8 ± 6.8 for EDV [P < 0.001] and 12.5 ± 5.3, 9.4 ± 4.2, and 8.3 ± 4.4 for ESV [P < 0.001]), resulting in a significantly decreased LVEF: 70.3% ± 9.1% vs. 75.2% ± 8.1% vs. 77.8% ± 9.3%, respectively (P < 0.001). CONCLUSION: The new CZT cameras yielded global LV function results different from those yielded by the conventional camera. LV volume was higher for the Discovery NM 530c than for the D-SPECT or the conventional camera, leading to decreased LVEF in healthy subjects. These differences should be considered in clinical practice and warrant the collection of a specific reference database.

Assessment of endothelial function and myocardial flow reserve using (15)O-water PET without attenuation correction.

PURPOSE: Myocardial blood flow (MBF) measurement using positron emission tomography (PET) from the washout rate of (15)O-water is theoretically independent of tissue attenuation. The aim of this study was to evaluate the impact of not using attenuation correction in the assessment of coronary endothelial function and myocardial flow reserve (MFR) using (15)O-water PET. METHODS: We retrospectively processed 70 consecutive (15)O-water PET examinations obtained at rest and during cold pressor testing (CPT) in patients with dilated cardiomyopathy (n = 58), or at rest and during adenosine infusion in heart transplant recipients (n = 12). Data were reconstructed with attenuation correction (AC) and without attenuation correction (NAC) using filtered backprojection, and MBF was quantified using a single compartmental model. The agreement between AC and NAC data was assessed using Lin's concordance correlation coefficient followed by Bland-Altman plot analysis. RESULTS: Regarding endothelial function, NAC PET showed poor reproducibility and poor agreement with AC PET data. Conversely, NAC PET demonstrated high reproducibility and a strong agreement with AC PET for the assessment of MFR. CONCLUSION: Non-attenuation-corrected (15)O-water PET provided an accurate measurement of MFR compared to attenuation-corrected PET. However, non-attenuation-corrected PET data were less effective for the assessment of endothelial function using CPT in this population.

First determination of the heart-to-mediastinum ratio using cardiac dual isotope (¹²³I-MIBG/99mTc-tetrofosmin) CZT imaging in patients with heart failure: the ADRECARD study.

PURPOSE: Cardiac innervation is assessed using the heart-to-mediastinum ratio (HMR) of metaiodobenzylguanidine (MIBG) on planar imaging using Anger single photon emission computed tomography (A-SPECT). The aim of the study was to determine the HMR of MIBG obtained using a CZT-based camera (D-SPECT; Spectrum Dynamics, Israel) in comparison with that obtained using conventional planar imaging. METHODS: The ADRECARD study prospectively evaluated 44 patients with heart failure. They underwent planar acquisition using the A-SPECT camera 4 h after (123)I-MIBG injection (236.4 ± 39.7 MBq). To localize the heart using D-SPECT, (99m)Tc-tetrofosmin (753 ± 133 MBq) was administered and dual isotope acquisition was performed using the D-SPECT system. HMR was calculated using both planar A-SPECT imaging and front view D-SPECT cine data. In a phantom study, we estimated a model fitting the A-SPECT and the D-SPECT data that was further applied to correct for differences between the cameras. RESULTS: A total of 44 patients (39 men and 5 women, aged 60 ± 11 years) with ischaemic (31 patients) and nonischaemic (13 patients) cardiomyopathy completed the study. Most patients (28 of 44) were NYHA class II, and the mean left ventricular ejection fraction was 33 ± 7 %. The mean HMR values were 1.34 ± 0.15 and 1.45 ± 0.27 from A-SPECT and D-SPECT, respectively (p < 0.0001). After correction, Lin's concordance correlation showed an almost perfect concordance between corrected D-SPECT HMR and A-SPECT HMR, and Bland-Altman analysis demonstrated a high agreement between the two measurements. CONCLUSION: The ADRECARD study demonstrated that determination of late HMR during cardiac MIBG imaging using dual isotope ((123)I and (99m)Tc) acquisition on a CZT camera (D-SPECT) is feasible in patients with heart failure. A linear correction based on the phantom study yielded a high agreement between (123)I MIBG HMR obtained using a CZT camera and that from conventional planar imaging.

Segmental and global left ventricular function assessment using gated SPECT with a semiconductor Cadmium Zinc Telluride (CZT) camera: phantom study and clinical validation vs cardiac magnetic resonance.

BACKGROUND: We evaluated gated-SPECT using a Cadmium-Zinc-Telluride (CZT) camera for assessing global and regional left ventricular (LV) function. METHODS: A phantom study evaluated the accuracy of wall thickening assessment using systolic count increase on both Anger and CZT (Discovery 530NMc) cameras. The refillable phantom simulated variable myocardial wall thicknesses. The apparent count increase (%CI) was compared to the thickness increase (%Th). CZT gated-SPECT was compared to cardiac magnetic resonance (CMR) in 27 patients. Global and regional LV function (wall thickening and motion) were quantified and compared between SPECT and CMR data. RESULTS: In the phantom study using a 5-mm object, the regression between %CI and %Th was significantly closer to the line of identity (y = x) with the CZT (R (2) = 0.9955) than the Anger (R (2) = 0.9995, P = .03). There was a weaker correlation for larger objects (P = .003). In patients, there was a high concordance between CZT and CMR for ESV, EDV, and LVEF (all CCC >0.80, P < .001). CZT underestimated %CI and wall motion (WM) compared to CMR (P < .001). The agreement to CMR was better for WM than wall thickening. CONCLUSION: The Discovery 530NMc provided accurate measurements of global LV function but underestimated regional wall thickening, especially in patients with increased wall thickness.

Tetrofosmin early time gated post-stress single-photon emission computed tomography imaging: feasibility and potential benefits.

BACKGROUND: The purpose of this study is to evaluate the feasibility, the image quality, and the clinical relevance of an early gated post-stress (GPS) single-photon emission computed tomography (SPECT) tetrofosmin (Myoview™-GE Healthcare) acquisition protocol. Time delay between myocardial technetium-labeled tracer administration and SPECT acquisition is usually about 30 minutes after stress, and 45 to 60 minutes at rest: because of the absence of significant redistribution, perfusion images are related to stress even 30 minutes after stress injection, while function and thickening data obtained with gated acquisition 30 minutes after stress are mainly related to rest conditions. METHODS: 194 patients were prospectively included and analyzed, in a multicenter registry. Three gated-SPECT 99(m)Tc-Tetrofosmin studies were performed per patient: GPS-SPECT, 30 minutes post-stress (GS30), and at rest (GR30). RESULTS: GPS image quality was excellent/good (93.9%), and similar to GS30 images (96.6%). The presence of adjacent myocardial sub-diaphragmatic activity on GPS images was similar to GS30 images (24% vs 22%), and less frequent than on GR30 images (31%). For perfusion, thickening, and motion scores, there was no significant difference between early and 30 minute post-stress in the global patient population, but significant differences were observed between GPS and GS30 for LVEF (65% ± 15% vs 63% ± 14%). In the ischemic patients, with the stress-rest protocol, the perfusion score was 14.2 on GPS images and 12.4 on GS30 images (P = .002). CONCLUSIONS: Tetrofosmin early GPS-SPECT is feasible without impairment of image quality (better count rate). Ischemic defect size on early post-stress images is slightly more pronounced than at 30 minutes: this could modify therapeutic decision. This technique produces reliable function information during early post-stress period, and might be useful for disclosing transient motion abnormalities.