Annals of Nuclear Medicine (v.32, #1)

Influence of region-of-interest determination on measurement of signal-to-noise ratio in liver on PET images by Shinji Amakusa; Koki Matsuoka; Masayuki Kawano; Kiyotaka Hasegawa; Mio Ouchida; Ayaka Date; Tsuyoshi Yoshida; Masayuki Sasaki (1-6).
On 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET), signal-to-noise ratio in the liver (SNRliver) is used as a metric to assess image quality. However, some regions-of-interest (ROIs) are used when measuring the SNRliver. The purpose of this study is to examine the different ROIs and volumes of interest (VOIs) to obtain a reproducible SNRliver.This study included 108 patients who underwent 18F-FDG-PET/CT scans for the purpose of cancer screening. We examined four different ROIs and VOIs; a 3-cm-diameter and a 4-cm-diameter circular ROI and a 3-cm-diameter and a 4-cm-diameter spherical VOI on the right lobe of the patients’ livers. The average of SUV (SUVmean), standard deviation (SD) of SUV (SUVSD), SNRliver and SD of the SNRliver obtained using ROIs and VOIs were then compared.Although the SUVmean was not different among the ROIs and VOIs, the SUVSD was small with a 3-cm-diameter ROI. The largest SUVSD was obtained with a 4-cm-diameter spherical VOI. The SNRliver and the SD of the SNRliver with a 4-cm-diameter spherical VOI were the smallest, while those with a 3-cm-diameter circular ROI were the largest. These results suggest that a small ROI may be placed on a relatively homogeneous region not representing whole liver unintentionally.The SNRliver varied according to the shape and size of ROIs or VOIs. A 4-cm-diameter spherical VOI is recommended to obtain stable and reproducible SNRliver.
Keywords: FDG-PET; Quality control; Image quality; Signal-to-noise ratio in the liver; Region of interest

Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid by Federico Caobelli; Agostino Chiaravalloti; Laura Evangelista; Giorgio Saladini; Orazio Schillaci; Manuela Vadrucci; Federica Scalorbi; Davide Donner; Pierpaolo Alongi (7-15).
The following affiliation should be added to the authors Agostino Chiaravalloti and Orazio Schillaci.Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5–8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of 18F-DOPA PET/CT in patients with recurrent MTC.60 patients (mean age 64 ± 13 years, range 44–82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging 18F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21 ± 11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of 18F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan–Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis. 18F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p = 0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p = 0.04). 18F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p < 0.001 and p = 0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC. 18F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.
Keywords: Medullary thyroid carcinoma; 18F-DOPA PET/CT; Prognostic value; Restaging

Impact of treatment delay in Radium-223 therapy of metastatic castration-resistant prostate cancer patients by Marie Øbro Fosbøl; Peter Meidahl Petersen; Gedske Daugaard; Søren Holm; Andreas Kjaer; Jann Mortensen (16-21).
Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities. The aim of this study was to assess whether prolonged interval between Ra-223 cycles to non-disease related causes had a negative impact on clinical outcome of therapy.Retrospective single-center study of mCRPC patients who initiated Ra-223 therapy in the period from March 2014 to February 2015. End points were number of completed Ra-223 cycles, overall survival (OS) and radiographic progression-free survival (rPFS). Bone scintigraphy, CT of thorax and abdomen, hematological status, PSA and alkaline phosphatase were evaluated prior to first dose and after 3rd and 6th treatment, respectively. Follow-up period was 18 months after first Ra-223 cycle.A total of 50 consecutive patients initiated Ra-223 therapy in the time period. Seventeen of 50 patients (34%) had prolonged interval between cycles due to delivery problems. Median delay was 4 weeks (range 3–9 weeks). Patients with delayed treatment had significantly longer median rPFS [delayed patients: 7.1 months (95% CI 4.9–9.3) vs. 4.5 months (95% CI 2.8–6.3)]. There was no significant difference in number of completed cycles or median OS.We find no negative impact of prolonged interval between Ra-223 cycles due to non-disease related reasons on OS, rPFS or number of completed treatment cycles.
Keywords: Radium-223; Prostate cancer; Bone metastases; Radionuclide therapy

Feasibility of combined risk stratification with coronary CT angiography and stress myocardial SPECT in patients with chronic coronary artery disease by Tomonari Kiriyama; Yoshimitsu Fukushima; Hiromitsu Hayashi; Hitoshi Takano; Shin-ichiro Kumita (22-33).
To examine the additional prognostic value of coronary CT angiography (CTA) over myocardial perfusion imaging (MPI) in patients with suspected or known coronary artery disease.A series of 157 patients (mean age 69 ± 9 years; 76% male; median follow-up 49 months; range 12–82 months) underwent stress MPI with SPECT and coronary CTA within a 6-month interval. Summed stress score (SSS) and summed difference score (SDS) of stress MPI, number of vessels with stenosis, and presence of left main trunk stenosis and high-risk plaques on coronary CTA were examined. Primary endpoints were cardiac death, acute myocardial infarction, or unstable angina requiring revascularization. Secondary endpoints were revascularization > 60 days after the latter imaging test. All patients were followed up for at least 1 year (mean 45 ± 19 months; range 12–82 months).Nine (6%) patients reached primary endpoints. Cardiac death occurred in 1 (0.6%) patient, myocardial infarction in 5 (3%), and unstable angina requiring hospitalization in 3 (2%). Elective revascularization within 60 days was performed in 31 (20%) patients. Sixteen (10%) patients required revascularization after > 60 days. Primary endpoint event-free survival rates were significantly lower in patients with myocardial ischemia (SDS ≥ 2) and high-risk plaques (HRP), and secondary endpoint event-free survival rates in patients with SSS ≥ 4 and 3VD. In multivariate analysis, Cox proportional hazards regression analysis revealed HRP (HR = 8.02; P = 0.006) and myocardial ischemia (HR = 11.487; P = 0.025) were significant predictors of primary endpoints, and 3VD of secondary endpoints (HR = 4.981; P = 0.008). Combined ischemia and HRP resulted in the significant increase of the model Chi square in prediction of primary end points from ischemia or HRP alone (17.4 vs. 9.41; P = 0.005, 17.4 vs. 9.39; P = 0.005, respectively).Coronary CT angiography may provide additional prognostic information over MPI.
Keywords: Myocardial perfusion imaging; Coronary computed tomography angiography; Risk stratification; Coronary artery disease; Ischemic heart disease

Evaluation of sequential SPECT and CT for targeted radionuclide therapy dosimetry by Tiantian Li; Nien-Yun Wu; Na Song; Greta S. P. Mok (34-43).
In targeted radionuclide therapy (TRT), a prior knowledge of the absorbed dose biodistribution is essential for pre-therapy treatment planning. Previously, we showed that non-rigid organ-by-organ registration in sequential quantitative SPECT images improved dose estimation. This study aims to investigate if sequential CT can further improve TRT dosimetric accuracy.We simulated SPECT/CT acquisitions at 1, 12, 24, 72 and 144 h In-111 Zevalin post-injection using an analytical MEGP projector, modeling attenuation, scatter and collimator-detector response. We later recruited a patient injected with 222 MBq In-111 DTPAOC imaged at 3 SPECT/CT sessions for clinical evaluations. Four registration schemes were evaluated: whole-body-based registration performed on sequential (1) SPECT (WB-SPECT) or (2) CT (WB-CT) images; organ-based registration applied on organs individually segmented from sequential (3) SPECT (O-SPECT) or (4) CT (O-CT) images. Voxel-by-voxel integration was performed followed by Y-90 voxel-S-kernel convolution. Organ-absorbed doses, iso-dose curves, dose–volume histograms (DVHs) were generated for targeted organs for analysis.In simulation study, organ-absorbed dose errors were (− 8.66 ± 2.83)%, (− 2.51 ± 3.69)%, (− 9.23 ± 3.28)%, (− 7.17 ± 2.53)% for liver, (− 14.81 ± 4.91)%, (− 3.60 ± 4.37)%, (− 18.13 ± 4.44)%, (− 11.34 ± 4.22)% for spleen, for O-SPECT, O-CT, WB-SPECT and WB-CT registrations, respectively. For all organs, O-CT showed superior results. Results of iso-dose contour, DVHs were in accordance with the organ-absorbed doses. In clinical studies, the results were also consistent which showed O-CT method deviated the most from the result with no registration.We conclude that if both sequential SPECT/CT scans are available, CT organ-based registration method can more effectively improve the 3D dose estimation. Sequential low-dose CT scans might be considered to be included in the standard TRT protocol.
Keywords: Targeted radionuclide therapy; Quantitative SPECT; CT; Dosimetry; Image registration

Prognostic value of FDG-PET and DWI in breast cancer by Kazuhiro Kitajima; Yasuo Miyoshi; Toshiko Yamano; Soichi Odawara; Tomoko Higuchi; Koichiro Yamakado (44-53).
To investigate the prognostic value of preoperative FDG-PET/CT and diffusion weighted imaging (DWI) in patients with breast cancer.A total of 73 patients with newly diagnosed invasive breast cancer who had undergone preoperative whole-body FDG-PET/CT and 3-Tesla breast MRI including DWI followed by surgery were identified. Effects of primary tumor PET parameters [maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and DWI parameters [mean apparent diffusion coefficient (ADCmean) and minimum ADC (ADCmin)] including clinicopathologic factors on disease-free survival (DFS) were retrospectively evaluated using the log-rank and Cox methods.After a median overall follow-up of 32.3 months in all patients, 6 (8.2%) of the 73 patients had recurrence. Receiver operating characteristic curve analysis and log-rank tests showed that patients with a high primary tumor SUVmax (≥ 3.60), MTV (≥ 3.15), and TLG (≥ 16.0) had a significantly lower DFS rate than those with a low SUVmax (< 3.60), MTV (< 3.15), and TLG (< 16.0), respectively (p = 0.0054, p = 0.0054, and p < 0.0001, respectively). SUVmean, ADCmean, and ADCmin were not significantly associated with recurrence. Univariate analysis showed that SUVmax (p = 0.0054), MTV (p = 0.0054), TLG (p < 0.0001), tumor size (p = 0.0083), estrogen receptor negativity (p = 0.046), progesterone receptor negativity (p = 0.0023), human epidermal growth factor receptor 2 positivity (p = 0.043), and the presence of axillary lymph node metastasis (p = 0.0037) were also significantly associated with recurrence. However, in multivariate analysis, none of them were an independent factor.The preoperative SUVmax, MTV, and TLG of primary breast cancer are prognostic factors for recurrence, whereas ADC values are not.
Keywords: Breast cancer; Prognosis; PET (positron emission tomography); DWI (diffusion weighted imaging); TLG (total lesion glycolysis)

Molecular imaging in musculoskeletal infections with 99mTc-UBI 29-41 SPECT/CT by Mike Sathekge; Osvaldo Garcia-Perez; Diana Paez; Noura El-Haj; Taylor Kain-Godoy; Ismaheel Lawal; Enrique Estrada-Lobato (54-59).
To determine the added value of CT over planar and SPECT-only imaging in the diagnosis of musculoskeletal infection using 99mTc-UBI 29-4.184 patients with suspected musculoskeletal infection who underwent planar and SPECT/CT imaging with 99mTc-UBI 29-41 were included. Planar, SPECT-only and SPECT/CT images were reviewed by two independent analysts for presence of bone or soft tissue infection. Final diagnosis was confirmed with tissue cultures, surgery/histology or clinical follow-up. 99mTc-UBI 29-41 was true positive in 105/184 patients and true negative in 65/184 patients. When differentiating between soft tissue and bone infection, planar + SPECT-only imaging had a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 95.0, 74.3, 84.8, 91.3 and 86.9%, respectively, versus 99.0, 94.5, 92.5, 98.5 and 94.5% for SPECT/CT. SPECT/CT resulted in a change in reviewers’ confidence in the final diagnosis in 91/184 patients. Inter-observer agreement was better with SPECT/CT compared with planar + SPECT imaging (kappa 0.87, 95% CI 0.71–0.85 versus kappa 0.81, 95% CI 0.58–0.75).Addition of CT to planar and SPECT-only imaging led to an increase in diagnostic performance and an improvement in reviewers’ confidence and inter-observer agreement in differentiating bone from soft tissue infection.
Keywords: 99mTc-UBI 29-41; SPECT/CT; Infection; Musculoskeletal

Tuberculosis (TB) still remains the world’s endemic infection. TB affects the lungs and any part of the body other than the lung. The diagnosis of TB has not changed much over the decades. Ethambutol is one of the first line treatments for TB. It can be labeled using 99mTc. 99mTc-ethambutol will be accumulated in the site of TB lesion and can be imaged using gamma camera. The aim of this study was to evaluate the diagnostic value of 99mTc-ethambutol scintigraphy in detecting and localizing of TB.Retrospective cross-sectional study was done. Subjects were patients suspected of having TB infection. Whole body and SPECT-CT imaging at the suspected area was done 1 and 4 h after injection of 370–555 MBq 99mTc-ethambutol. 99mTc-ethambutol scintigraphy was analyzed visually. The results were compared with that of histopathological or microbiological tests. Statistical analysis was done to determine the sensitivity, specificity, PPV, NPV and accuracy.One hundred and sixty-eight subjects were involved in this study. There were 110 men and 58 women with mean age of 34.52 ± 11.94 years. There were concordance results in 156 (92.86%) and discordant in 12 (7.14%) subjects between 99mTc-ethambutol scintigraphy and histopathological or microbiological result. The sensitivity, specificity, PPV, NPV and accuracy of 99mTc-ethambutol scintigraphy in the diagnosis of pulmonary TB were 93.9, 85.7, 93.9, 85.7 and 91.4%, respectively, for extra-pulmonary TB 95.5, 77.8, 97.9, 63.6, and 85.1%, respectively, and for total tuberculosis 94.9, 83.3, 96.3, 78.1 and 92.8%, respectively. There was no side effect observed in this study. 99mTc-ethambutol scintigraphy is a useful diagnostic imaging technique to detect and localize intra- and extra-pulmonary TB. It is safe to be performed even in pediatric patient. Consuming ethambutol less than 2 weeks did not influence the result.
Keywords: Pulmonary; Extra-pulmonary tuberculosis; SPECT/CT imaging; 99mTc-ethambutol

Low levels of PSMA expression limit the utility of 18F-DCFPyL PET/CT for imaging urothelial carcinoma by Scott P. Campbell; Alexander S. Baras; Mark W. Ball; Max Kates; Noah M. Hahn; Trinity J. Bivalacqua; Michael H. Johnson; Martin G. Pomper; Mohamad E. Allaf; Steven P. Rowe; Michael A. Gorin (69-74).
To explore the clinical utility of PSMA-targeted 18F-DCFPyL PET/CT in patients with metastatic urothelial carcinoma.Three patients with metastatic urothelial carcinoma were imaged with 18F-DCFPyL PET/CT. All lesions with perceptible radiotracer uptake above background were considered positive. Maximum standardized uptake values were recorded for each detected lesion and findings on 18F-DCFPyL PET/CT were compared to those on conventional imaging studies. To further explore PSMA as a molecular target of urothelial carcinoma, RNA-sequencing data from The Cancer Genome Atlas were used to compare the relative expression of PSMA among cases of bladder cancer, prostate cancer, and clear cell renal cell carcinoma. Additionally, immunohistochemical staining for PSMA was performed on a biopsy specimen from one of the imaged patients. 18F-DCFPyL PET/CT allowed for the detection of sites of urothelial carcinoma, albeit with low levels of radiotracer uptake. Analysis of RNA-sequencing data revealed that bladder cancer had significantly lower levels of PSMA expression than both prostate cancer and clear cell renal cell carcinoma. Consistent with this observation, immunohistochemical staining of tissue from one of the imaged patients demonstrated a low level of neovascularization and nearly absent PSMA expression.The relatively scant expression of PSMA by urothelial carcinoma likely limits the utility of PSMA-targeted PET imaging of this malignancy. Future research efforts should focus on the development of other molecularly targeted imaging agents for urothelial carcinoma.
Keywords: Prostate-specific membrane antigen; PSMA; 18F-DCFPyL PET/CT; Urothelial carcinoma; Bladder cancer; Transitional cell carcinoma