Annals of Nuclear Medicine (v.27, #2)

Serum tumor markers and PET/CT imaging for tumor recurrence detection by Vibeke Kruse; Veronique Cocquyt; Marleen Borms; Alex Maes; Christophe Van de Wiele (97-104).
When confronted with a suspicious rise in CA 15.3 in asymptomatic breast cancer patients following primary treatment and negative or equivocal conventional imaging findings, FDG PET/CT allows assessment of the site and extent of the recurring disease with an accuracy of 83 %. Both FDG PET and FDG PET/CT are superior when compared to CT alone for the purpose of recurrence detection in patients suffering from ovarian carcinoma who have completed primary therapy but demonstrate a rising serum CA-125 level. As the global accuracy of CT alone for detection of recurrence of ovarian cancer approximates 80 %, CT scan should be performed upfront to identify the site of recurrence. When confronted with negative or equivocal CT findings, FDG PET alone or FDG PET/CT should be added. In patients with rising serum CEA levels that have undergone primary treatment for a colorectal carcinoma, both FDG PET and FDG PET/CT allow detection of tumor recurrence with an accuracy of 95 %, well above that of CT and MRI. Available studies further suggest that FDG/PET findings will affect treatment management in 28–50 % of these patients. The detection rate of both 11C-choline and 18F-choline PET and PET/CT for local, regional, and distant recurrence in prostate carcinoma patients with a biochemical recurrence increases with rising PSA value at the time of imaging and reaches about 75 % in patients with PSA >3 ng/mL. Furthermore, PET and PET/CT with [11C]- and [18F]-choline derivates may be helpful in the clinical setting for optimization of individualized treatment.
Keywords: Serum tumor markers; PET/CT

Imaging assessment of enthesitis in spondyloarthritis by Yoshinori Taniguchi; Yoshitaka Kumon; Tomoya Takata; Shigetoshi Sano; Takenao Ohnishi; Munenobu Nogami; Yasuhiro Ogawa; Yoshio Terada (105-111).
Enthesitis, defined as the inflammation of the origin and insertion of ligaments, tendons, aponeuroses, annulus fibrosis, and joint capsules, is a hallmark of spondyloarthritis (SpA). New imaging techniques including magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography with computed tomography using 18F-fluorodeoxyglucose capable of detecting morphological and metabolic abnormalities and monitoring disease activity have improved the assessment and management of enthesitis of SpA.
Keywords: Enthesitis; Spondyloarthritis; Ultrasonography; Magnetic resonance imaging; FDG-PET/CT

Predictors of post-stress LVEF drop 6 months after reperfused myocardial infarction: a gated myocardial perfusion SPECT study by C. Guenancia; A. Cochet; O. Humbert; I. Dygai-Cochet; L. Lorgis; M. Zeller; K. Stamboul; F. Brunotte; Y. Cottin (112-122).
To identify the predictive factors of myocardial stunning as assessed by the drop in post-stress Left Ventricular Ejection Fraction (LVEF) in patients with a recent history of myocardial infarction (MI).We prospectively included 215 consecutive patients admitted for acute MI who underwent percutaneous coronary intervention with a greater than or equal to grade-3 TIMI flow in the culprit vessel. Six months after discharge, a post-stress/rest 99mTc-sestamibi gated SPECT was performed. The perfusion score was evaluated visually using a 17-segment model. The LVEF drop was considered significant if the post-stress LVEF was ≥5 % below the rest LVEF (QGS® software).A post-stress LVEF drop was observed in 51 (24 %) patients. Patients with an LVEF drop were more likely than patients with a stable post-stress LVEF to have diabetes (22 % vs. 10 %, p = 0.048), significant ischemia (SDS > 2) (51 % vs. 28 % p = 0.003) and higher rest LVEF [62 % (56–69) vs. 56 % (49–63) p < 0.001]. In contrast, summed rest score, related to infarct size, did not differ between the groups. Multivariate logistic regression analysis identified SDS > 2 (OR 3.78, 95 % CI 1.8–7.92, p < 0.001), diabetes (OR 3.35, 95 % CI 1.33–8.49; p = 0.011) and rest LVEF (OR 1.08, 95 % CI 1.04–1.12, p < 0.001) as independent explanatory variables of an LVEF drop.In patients with recent MI and post-procedural grade-3 TIMI flow, ischemia and diabetes were independent predictive factors of myocardial stunning. The higher incidence of reversible perfusion abnormalities validates the model of myocardial stunning in the post-MI period, and excludes the potential involvement of myocardial necrosis.
Keywords: Myocardial stunning; Myocardial infarction; gSPECT; Diabetes; Left ventricular ejection fraction

Iodine-123 metaiodobenzylguanidine imaging can predict future cardiac events in Japanese patients with Parkinson’s disease by Terufumi Kinbara; Tomoko Hayano; Nozomu Otani; Yuhji Furutani; Schinichiro Tanaka (123-131).
Iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy provides useful diagnostic information in differentiating Parkinson’s disease (PD) from other neurological diseases. Moreover, a number of studies have reported that 123I-MIBG imaging provides powerful diagnostic and prognostic information in congestive heart failure (HF) patients. The aim of the present study was to investigate the cardiovascular predictive value of cardiac 123I-MIBG imaging in patients with PD.Seventy-eight patients with PD were retrospectively studied. All patients underwent 123I-MIBG imaging at 30 min (early) and 240 min (delayed) after the tracer injection, and clinical parameters were also investigated.During a mean follow-up of 27 ± 12 months, 5 patients required hospitalization for HF. There were no occurrences of myocardial infarction, fatal arrhythmia or sudden death. There was no significant coronary artery stenosis, significant valvular heart disease, or cardiomyopathy in the HF patients. The left ventricular ejection fraction (LVEF) was normal in the HF patients. 123I-MIBG delayed heart to mediastinal ratio (delayed H/M) was lower and washout rate (WR) was higher in HF patients than non-HF patients (1.62 ± 0.21 vs. 1.34 ± 0.08, p = 0.019; 31.9 ± 5.5 vs. 38.2 ± 3.3, p = 0.005, respectively). Both WR and delayed H/M did not correlate with Hoehn and Yahr stage. The WR showed a weak negative correlation with delayed H/M (R = −0.357, p < 0.001) upon simple linear regression analysis. A multivariate Cox regression analysis revealed that WR and delayed H/M were independently associated with HF (p = 0.014, p = 0.029, respectively). Kaplan–Meier analysis revealed that patients with abnormal WR (>37 %) and delayed H/M (<1.48) had a higher incidence of HF than those with normal WR and delayed H/M (p = 0.014, p = 0.04, respectively).WR showed stronger predictive power than delayed H/M in Kaplan–Meier analysis. WR has more useful cardiovascular predictive value than delayed H/M in Japanese patients with PD. Further studies are needed to clarify the significance of abnormal MIBG uptake in PD patients.
Keywords: 123I-MIBG myocardial scintigraphy; Parkinson’s disease; Heart failure

Myocardial perfusion SPECT (MPS) is a noninvasive method commonly used for assessment of the hemodynamic significance of intermediate coronary stenoses. Fractional flow reserve (FFR) measurement is a well-validated invasive method used for the evaluation of intermediate stenoses. We aimed to determine the association between MPS and FFR findings in intermediate degree stenoses and evaluate the added value of quantification in MPS.Fifty-eight patients who underwent intracoronary pressure measurement in the catheterization laboratory to assess the physiological significance of intermediate (40–70 %) left anterior descending (LAD) artery lesions, and who also underwent stress myocardial perfusion SPECT either for the assessment of an intermediate stenosis or for suspected coronary artery disease were analyzed retrospectively in the study. Quantitative analysis was performed using the 4DMSPECT program, with visual assessment performed by two experienced nuclear medicine physicians blinded to the angiographic findings. Summed stress scores (SSS) and summed difference scores (SDS) in the LAD artery territory according to the 20 segment model were calculated. A summed stress score of ≥3 and an SDS of ≥2 were assumed as pathologic, indicating significance of the lesion; a cutoff value of 0.75 was used to define abnormal FFR. Both visual and quantitative assessment results were compared with FFR using Chi-square (χ²) test.The mean time interval between two studies was 13 ± 11 days. FFR was normal in 45 and abnormal in 13 patients. Considering the FFR results as the gold standard method for assessing the significance of the lesion, the sensitivity and specificity of quantitative analysis determining the abnormal flow reserve were 85 and 84 %, respectively, while visual analysis had a sensitivity of 77 % and a specificity of 51 %. There was a good agreement between the observers (κ = 0.856). Summed stress and difference scores demonstrated moderate inverse correlations with FFR values (r = −0.542, p < 0.001 and r = −0.506, p < 0.001, respectively).Quantitative analysis of the myocardial perfusion SPECT increases the specificity in evaluating the significance of intermediate degree coronary lesions.
Keywords: Intermediate degree coronary artery stenosis; Myocardial perfusion SPECT; Fractional flow reserve; Functional significance

Is further evaluation needed for incidental focal uptake in the prostate in 18-fluoro-2-deoxyglucose positron emission tomography–computed tomography images? by Insang Hwang; Ari Chong; Seung-Il Jung; Eu-Chang Hwang; Sun-Ouck Kim; Taek-Won Kang; Dong-Deuk Kwon; Kwangsung Park; Soo-Bang Ryu (140-145).
The aim of this study was to investigate the frequency of secondary evaluation to detect prostate cancer that was primarily manifested as abnormal hypermetabolism detected by 18-fluoro-2-deoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT). We also evaluated the association of maximum standardized uptake values (SUVmax) on PET/CT with clinicopathologic results.We evaluated PET/CT reports from a total of 12,037 patients to find cases with abnormal prostate hypermetabolism. Patients with known prostate cancer or a recent prostate procedure were excluded. We analyzed the frequency of secondary evaluations such as digital rectal exams (DRE), levels of serum prostate-specific antigen (PSA), and/or biopsy to confirm prostate cancer. Biopsied patients were categorized into benign and cancer groups. Clinicopathologic characteristics were compared between the groups.Among 12,037 PET/CT images, 184 (1.5 %) showed abnormal hypermetabolism in the prostate. Secondary evaluation was carried out in 120 patients. Biopsy was performed in 38 patients and prostate cancer was confirmed in 23 patients. The median serum PSA level was 3.2 and 49.7 ng/mL in the benign group and cancer group, respectively. The SUVmax was higher in the cancer group (5.7 ± 5.1) than in the benign group (4.8 ± 2.7), but the difference was not statistically significant (p = 0.37). In the cancer group, a high serum PSA level (≥20 ng/mL) was detected in 78.3 % of the patients. The Gleason score was 7 in 34.7 % and 8–10 in 56.5 % of prostate cancer patients.Hypermetabolism in the prostate was incidentally detected in 1.5 % of patients, and only 65.2 % of these patients underwent further evaluation (DRE and/or serum PSA levels). Among cases of incidentally detected hypermetabolism in the prostate, patients with abnormal findings (DRE and/or PSA levels) showed high positivity by biopsy, and more than two-thirds of the positive biopsies showed significant prostate cancer. Therefore, patients with hypermetabolism in the prostate should not be ignored and should be secondarily evaluated by DRE and PSA level.
Keywords: Prostate cancer; Positron emission tomography/computed tomography; Fluorodeoxyglucose F18

Role of F-18 FDG PET/CT in assessing bone marrow involvement in pediatric Hodgkin’s lymphoma by Kanhaiyalal Agrawal; Bhagwant Rai Mittal; Deepak Bansal; Neelam Varma; Radhika Srinivasan; Amita Trehan; Kuruva Manohar; Raghava Kashyap; Anish Bhattacharya; Ram K. Marwaha (146-151).
The aim of the current study was to assess the utility of F-18-fluoro-2-deoxy-d-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared to bone marrow biopsy (BMB) in initial staging of Hodgkin’s lymphoma (HL) in pediatric patients.Data of 38 pediatric patients (mean age 9.8 years, range 3–18 years) with HL were analyzed for the involvement of bone marrow. All patients underwent non-contrast F-18 FDG PET/CT study. BMB was done in 31 patients from the bilateral iliac crests. Scans were interpreted by two nuclear medicine physicians blinded to the details of BMB.Of the 31 patients who underwent BMB, 5 patients had lymphomatous involvement on BMB. PET/CT was positive in four of these five patients. In 26 patients negative on BMB, PET was negative in 23 patients and positive in 3 patients for BMI. The sensitivity and negative predictive value of F-18 FDG PET/CT was 87.5 and 96 %, respectively, for BMI.F-18 FDG PET/CT can predict BMB results with high accuracy. F-18 FDG PET/CT may be used at initial staging of pediatric Hodgkin’s lymphoma as it uncovers unsuspected BMI and BMB may be omitted in patients with PET-positive BMI.
Keywords: Pediatric Hodgkin’s lymphoma; Bone marrow involvement; Bone marrow biopsy; FDG; PET/CT

MRI-guided attenuation correction in whole-body PET/MR: assessment of the effect of bone attenuation by A. Akbarzadeh; M. R. Ay; A. Ahmadian; N. Riahi Alam; H. Zaidi (152-162).
Hybrid PET/MRI presents many advantages in comparison with its counterpart PET/CT in terms of improved soft-tissue contrast, decrease in radiation exposure, and truly simultaneous and multi-parametric imaging capabilities. However, the lack of well-established methodology for MR-based attenuation correction is hampering further development and wider acceptance of this technology. We assess the impact of ignoring bone attenuation and using different tissue classes for generation of the attenuation map on the accuracy of attenuation correction of PET data.This work was performed using simulation studies based on the XCAT phantom and clinical input data. For the latter, PET and CT images of patients were used as input for the analytic simulation model using realistic activity distributions where CT-based attenuation correction was utilized as reference for comparison. For both phantom and clinical studies, the reference attenuation map was classified into various numbers of tissue classes to produce three (air, soft tissue and lung), four (air, lungs, soft tissue and cortical bones) and five (air, lungs, soft tissue, cortical bones and spongeous bones) class attenuation maps.The phantom studies demonstrated that ignoring bone increases the relative error by up to 6.8 % in the body and up to 31.0 % for bony regions. Likewise, the simulated clinical studies showed that the mean relative error reached 15 % for lesions located in the body and 30.7 % for lesions located in bones, when neglecting bones. These results demonstrate an underestimation of about 30 % of tracer uptake when neglecting bone, which in turn imposes substantial loss of quantitative accuracy for PET images produced by hybrid PET/MRI systems.Considering bones in the attenuation map will considerably improve the accuracy of MR-guided attenuation correction in hybrid PET/MR to enable quantitative PET imaging on hybrid PET/MR technologies.
Keywords: PET/MRI; PET/CT; Attenuation correction; Tissue classification; Quantification

Dual-time-point F-18 FDG PET/CT imaging for differentiating the lymph nodes between malignant lymphoma and benign lesions by Michihiro Nakayama; Atsutaka Okizaki; Shunta Ishitoya; Miki Sakaguchi; Junichi Sato; Tamio Aburano (163-169).
The purpose of the present study is to evaluate the clinical value of dual-time-point F-18 FDG PET/CT imaging to differentiate malignant lymphoma (ML) from benign lymph node (BLN).The subjects were 310 lymph nodes in 84 patients (195 ML lesions in 30 patients and 115 BLN in 54 patients associated with various etiologies.). F-18 FDG PET/CT scan was performed at 50 min (early scan) and at 100 min (delayed scan) after the injection. First, the maximum standardized uptake value (SUVmax) of each lesion at early and delayed scans was calculated. Second, we estimated the difference between early and delayed SUVmax (D-SUVmax) and the retention index (RI-SUVmax) to evaluate the change of tracers in the lesions. Furthermore, proper cut-off values of them were evaluated using receiver operating characteristic analysis. The efficacy of each parameter was analyzed with ANOVA.Delayed SUVmax and D-SUVmax in ML were significantly higher than those in BLN. Proper cut-off value in delayed SUVmax was 4.0 and in D-SUVmax was 1.0. When the proper cut-off value in D-SUVmax was applied, the D-SUVmax yielded the role of diagnosis with sensitivity of 82.6 %, specificity of 65.2 %, positive predictive value of 80.1 % and negative predictive value of 68.8 %, respectively.The delayed SUVmax and D-SUVmax were useful indices to differentiate ML from BLN, regardless of histologic subtype. Dual-time-point F-18 FDG PET/CT imaging may help to consider whether there is any need to proceed to more invasive tests, such as biopsy, in individual patients.
Keywords: 18F-FDG PET/CT; Dual-time-point imaging; Lymphoma; Benign lymph node; Standardized uptake value

The role of DMSA renal scintigraphy in the first episode of urinary tract infection in childhood by Suroj Supavekin; Wantanee Surapaitoolkorn; Nantiya Pravisithikul; Siwinee Kutanavanishapong; Sunanta Chiewvit (170-176).
The role of dimercaptosuccinic acid (DMSA) renal scintigraphy in the first episode of urinary tract infection (UTI) has been the subject of debate for many years. The aim of this study was to evaluate the relationship of voiding cystourethrography (VCUG), renal ultrasonography and DMSA renal scintigraphy and to detect renal parenchymal changes by performing DMSA renal scintigraphy at 6 months after the first episode of UTI.A prospective study was conducted in 67 hospitalized children (46 boys, 21 girls). Mean age of the patients was 0.97 ± 1.57 years (0.02–7.26 years). All children received VCUG, renal ultrasonography and DMSA renal scintigraphy. DMSA renal scintigraphy was performed at 1 and 6 months after UTI.Of 67 children, 17 (25.4 %), 23 (34.3 %) and 20 (29.9 %) had vesicoureteral reflux (VUR), abnormal renal ultrasonography and abnormal DMSA renal scintigraphy, respectively. Unilateral hydronephrosis had a significant correlation with VUR at p value 0.024. In renal units, abnormal renal ultrasonography and hydronephrosis had significant correlations with VUR at p values 0.039 and 0.021, respectively. In patients and renal units, hydronephrosis had no significant correlation with abnormal DMSA renal scintigraphy at 1 month after UTI. However, abnormal renal ultrasonography and VUR had significant correlations with abnormal DMSA renal scintigraphy at p values 0.022 and <0.001 in patients and at p values 0.024 and <0.001 in renal units, respectively. Both in patients and renal units, VUR (Grade I–III) had no significant correlation with abnormal DMSA renal scintigraphy. However, severe VUR (Grade IV–V) had significant correlations with abnormal DMSA renal scintigraphy at p values <0.001 and <0.001, respectively. Seventeen patients underwent DMSA renal scintigraphy at 6 months after UTI. In addition, 15 (88.2 %) developed persistent renal scarring.Abnormal renal ultrasonography and severe VUR identify renal parenchymal changes. DMSA renal scintigraphy in the first episode of UTI should be carried out in those patients. Abnormal DMSA renal scintigraphy at 1 month after UTI has a tendency to persist.
Keywords: DMSA renal scintigraphy; Urinary tract infection; Renal scarring

To evaluate the correlation between change in FDG uptake before and after chemotherapy in hepatic metastases of colorectal carcinoma (HCRC) and a histopathologic tumor regression grade (TRG).In patients with HCRC, PET/CT data prior to hepatic surgery were retrospectively analyzed under an IRB waiver. The maximum standard uptake value (SUVmax) was measured before and after chemotherapy. The relative change of FDG activity in the identified lesions was calculated (dSUV). Histopathological specimens of resected metastases were graded on a 5-score TRG scale. A TRG of 1–3 was rated as a responding to therapy, whereas TRG 4–5 were regarded as non-responding lesions.31 lesions were identified in 23 patients. Mean SUVmax before and after therapy was 6.9 ± 3.7 and 3.5 ± 1.8, respectively. The area under the receiver operator characteristic curve revealed a conclusive correlation between TRG and dSUV (AUC 0.773; 95 % confidence interval 0.599–0.946) with a cut off at 41 % decrease in FDG activity yielding a sensitivity and specificity of 72 and 75 %, respectively.A relative change in FDG activity (dSUV) of more than 41 % decrease correlated significantly with histopathological tumor regression and might be a prognostic tool for response to chemotherapy in HCRC.
Keywords: FDG PET/CT; Tumor regression grade; Colorectal cancer; Hepatic metastasis; Therapy response assessment