Annals of Nuclear Medicine (v.25, #6)

This study was designed to assess the value of a combinatorial protocol, namely, stress only myocardial perfusion SPECT (MPS), 64-slice coronary computed tomographic angiography (CTA), and SPECT/CTA 3-dimensional (3D) fusion imaging for the evaluation of coronary artery disease.A total of 142 patients were retrospectively reviewed. All underwent stress only MPS and 64-slice CTA before invasive coronary angiography (ICA). The SPECT/CTA 3D fusion images were generated. We compared the results of the combinatorial protocol with ICA.Seventy nine (76.0%) subjects were found to have ≥50% stenoses, by ICA. The sensitivity of the combinatorial examination was 100% and its specificity 80.8%. Its positive and negative predictive values were 94.0 and 100%, respectively. The number of lesion for abnormal MPS with matching significant stenoses on CTA is 94 [43 in left anterior descending (LAD); 19 in left circumflex (LCX); 32 in right coronary artery (RCA)], the number of lesion for equivocal perfusion defect with matching stenoses on CTA is 24 (14 in LAD; 7 in LCX; 3 in RCA). The number of coronary arterial stenoses without MPS abnormality is 10, 4 stenoses were detected in left main lesion and the other stenoses were comparatively mild lesion in multi-vessel disease.Stress only MPS/CTA 3D fusion imaging could provide the potential for improved diagnostic accuracy and additional information of hemodynamically relevant coronary arterial stenoses.
Keywords: Myocardial perfusion imaging; SPECT; CT angiography; Fusion image; Myocardial ischemia

Validation of reference tissue modelling for [11C]flumazenil positron emission tomography following head injury by Thomas Geeraerts; Jonathan P. Coles; Franklin I. Aigbirhio; John D. Pickard; David K. Menon; Tim D. Fryer; Young T. Hong (396-405).
[11C]Flumazenil ([11C]FMZ) positron emission tomography (PET) can be used as a measure of neuronal loss. The purpose of this study was to validate reference tissue kinetic modelling of [11C]FMZ PET within a group of patients with head injury.Following earlier studies, the pons was used as the reference region. PET scans were performed on 16 controls and 11 patients at least 6 months following injury, each of whom also had arterial blood sampling to provide whole blood and metabolite-corrected plasma input functions. Regional non-displaceable binding potentials (BPND) were calculated from five reference tissue models and compared to BPND from arterial input models. For the patients, the regions included a peri-lesional region of interest (ROI).Total distribution volume of the pons was not significantly different between control and patient groups (P = 0.24). BPND from all the reference tissue approaches correlated well with BPND from the plasma input models for both controls (r 2 = 0.98–1.00; P < 0.001) and patients (r 2 = 0.99–1.00; P < 0.001). For the peri-lesional regions (n = 11 ROI values), the correlation was also high (r 2 = 0.91).These results indicate that reference tissue modelling with the pons as the reference region is valid for [11C]FMZ PET in head-injured patients at 6 months following injury within both normal appearing and peri-lesional brain regions.
Keywords: [11C]Flumazenil; Kinetic modelling; Positron emission tomography (PET); Reference tissue; Traumatic brain injury (TBI)

Evaluation of outcome prediction and disease extension by quantitative 2-deoxy-2-[18F] fluoro-d-glucose with positron emission tomography in patients with small cell lung cancer by Nuri Arslan; Murat Tuncel; Okan Kuzhan; Engin Alagoz; Burcin Budakoglu; Ahmet Ozet; Mehmet Ali Ozguven (406-413).
The objective of this study is to determine whether 2-deoxy-2-[18F] fluoro-d-glucose with positron emission tomography (FDG-PET) imaging and quantitative PET parameters can predict outcome and differentiate patients with limited disease (LD) from extensive disease (ED) in patients with small cell lung cancer (SCLC).We retrospectively evaluated data from 25 patients who underwent either initial staging (Group A, n 12) or restaging (Group B, n 13) by conventional imaging methods and FDG-PET according to the simplified staging scheme developed by the Veterans Administration Lung Cancer Study Group-2. FDG-PET images were both visually and quantitatively evaluated with SUVmax, SUVave, total metabolic tumor volume (with SUVmax > %50 and SUVmax > 2.5), total lesion glycolysis (TLG) (with SUVmax > %50 and SUVmax > 2.5). The correlation between quantitative PET parameters, disease stages and survival were analyzed.By conventional methods 14 of 25 (56%) patients were reported to have LD and 11 of 25 (44%) had ED. FDG-PET scan upstaged 9 out of 25 (36%) and downstaged 2 out of 25 (%8) patients. Among the quantitative PET parameters, TLGs were the only PET parameters that differentiated between Group A and Group B patients. FDG-PET staging (p = 0.019) could predict significant survival difference between stages on contrary to conventional staging (p = 0.055). Moreover, TLG [SUVmax > %50] was the only quantitative PET parameter that could predict survival (p = 0.027).FDG-PET imaging is a valuable tool in the management of patients with SCLC for a more accurate staging. The use of quantitative PET parameters may have a role in prediction of stage and survival.
Keywords: FDG-PET; Small cell lung cancer; Staging; Quantitative PET

Phase I clinical study of NMK36: a new PET tracer with the synthetic amino acid analogue anti-[18F]FACBC by Yuji Asano; Yusuke Inoue; Yasuhiko Ikeda; Kei Kikuchi; Toshimasa Hara; Chikako Taguchi; Takanori Tokushige; Hideki Maruo; Tohoru Takeda; Tomomi Nakamura; Tomoe Fujita; Yuji Kumagai; Kazushige Hayakawa (414-418).
NMK36 is a novel PET tracer containing a synthetic amino acid analogue anti-[18F]FACBC as the active ingredient, and is under development for the use of tumor diagnosis. A Phase I clinical study of NMK36 was conducted to evaluate its safety, biodistribution, and radiation dosimetry in healthy volunteers.Six healthy volunteers (Japanese male) received a bolus injection of NMK36 (174.4–201.4 MBq) intravenously. The safety of NMK36 was evaluated by monitoring signs/symptoms, electrocardiography, recording vital signs, and laboratory examinations at baseline and several time points in 6 days after injection. A total of 11 whole-body PET-CT scans were acquired up to 4 h post-injection, and venous blood and urine samples were also collected for 6 and 24 h post-injection, respectively. Based on the results of the biodistribution study, absorbed radiation dose was estimated by the MIRD method.Although two adverse events occurred after the injection of NMK36, they were mild and disappeared without any specific treatment. NMK36 preferentially accumulated in the pancreas and liver early after injection, followed by rapid clearance from the pancreas. Persistent uptake was observed in the skeletal muscle. NMK36 showed low uptake in the brain, and its urinary excretion was limited (5.40 ± 1.43% of the injected dose at 24 h post-injection). The liver was the critical organ, with a mean absorbed dose of 40.6 μGy/MBq. The estimated effective dose of NMK36 was 13.8 μSv/MBq, which was similar to or lower than those of radiotracers approved for clinical use including [18F]FDG.The findings of this study indicate that NMK36 is well tolerated. NMK36 has favorable characteristics for imaging brain and pelvic tumors, such as low brain uptake, slow urinary excretion, and high in vivo stability.
Keywords: PET; Anti-[18F]FACBC; Amino acid; NMK36; Phase I

Long-term prognostic stratification by a combination of 123I-metaiodobenzylguanidine scintigraphy and ejection fraction in dilated cardiomyopathy by Mitsuru Momose; Dai Okayama; Hitoshi Nagamatsu; Chisato Kondo; Nobuhisa Hagiwara; Shuji Sakai (419-424).
123I-metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for predicting the prognosis in patients with congestive heart failure; however, little is known regarding long-term prognostic evaluations. The aim of this study was to evaluate long-term prognosis in a roughly 10-year period, in dilated cardiomyopathy (DCM) by MIBG imaging, compared to other conventional functional parameters.Eighty-six DCM patients (50 ± 14 years of age, 57 males) underwent MIBG imaging, at 15 min and 4 h after tracer injection, from which the delayed heart to mediastinum ratio (H/M) and washout rate (WR) were obtained. The left ventricular ejection fraction (EF) and end-diastolic diameter (LVDd) were also measured by echocardiogram. All patients were followed up for 8–14 years, and the death event was investigated.Kaplan–Meier curves revealed a poor prognosis only in the group above the third quartile of WR (=50%) (10-year prognosis, 35%); however, there were no statistically significant differences in prognosis among the other 3 groups (10-year prognosis, 75–84%). A Cox hazard univariate analysis selected WR (p = 0.0004), H/M (p < 0.0001), EF (p = 0.0024), and LVDd (p = 0.0189) as significant prognostic indicators. Multivariate analysis revealed the H/M (p = 0.0023) and EF (p = 0.024) to be an independent prognostic predictor. The 10-year prognosis of patients with both WR < 50% and EF > 30%; WR < 50% and EF < 30%; and both WR > 50% and EF < 30% were 89, 71, and 33%, respectively. These three groups were well stratified, significantly (log-rank test: χ 2 = 30.0, p < 0.0001). However, even patients with WR ≥ 50% had few death events after 3 years following MIBG imaging.The MIBG parameter, delayed H/M or WR combined with the EF is a useful tool for the prediction of a long-term prognosis in DCM, which is superior to MIBG parameters alone. However, patients with WR > 50% but no event in a 3-year follow-up period should undergo an additional MIBG imaging for prognostic prediction.
Keywords: 123I-metaiodobenzylguanidine (MIBG); Dilated cardiomyopathy; Washout rate

This study aimed to assess the outcome of high-dose In-111 octreotide treatment and efficacy of long-acting Sandostatin LAR in patients with disseminated neuroendocrine tumors.A total of 14 patients (mean age 51.8 ± 13.2 years; 10 female, 4 male) receiving high-dose In-111 octreotide in our centre for the treatment of neuroendocrine tumors were included in the study. Monthly treatment with long-acting somatostatin analogue [Sandostatin long-acting release (Novartis Pharmaceuticals)] was continued in nine cases.During a 3-year period, a total of 45 courses of high-dose In-111 octreotide treatment were delivered to 14 patients. In seven patients receiving an average of four treatment courses (6 carcinoid tumors, 1 thymoma, patients: 2, 4, 5, 11–14) stable disease was achieved (50%). In two patients with carcinoid tumors (patients 1 and 3) who received four treatment courses, partial response was observed (14%). Five patients (36%; 4 NET, 1 gastrinoma; patients 6–10) died due to progressive disease following on average two treatment courses. On average, deaths occurred 2 months after the last treatment dose. No complete responses were seen. Partial response was achieved in two of the nine patients receiving Sandostatin LAR, while four had stable disease. Both treatments were associated with acceptable tolerability.High-dose In-111 octreotide can be safely administered in conjunction with somatostatin analogue in patients with disseminated NET and this treatment may help to stabilize the disease.
Keywords: In-111 octreotide; Neuroendocrine tumors; Sandostatin; Treatment response

Does adding FDG-PET to MRI improve the differentiation between primary cerebral lymphoma and glioblastoma? Observer performance study by Keishi Makino; Toshinori Hirai; Hideo Nakamura; Ryuji Murakami; Mika Kitajima; Yoshinori Shigematsu; Rumi Nakashima; Shinya Shiraishi; Hiroyuki Uetani; Koya Iwashita; Masuma Akter; Yasuyuki Yamashita; Jun-ichi Kuratsu (432-438).
It is sometimes difficult to distinguish between primary central nervous system lymphomas (PCNSL) and glioblastoma multiforme (GBM). The aim of this study was to investigate whether the addition of 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography ([18F]FDG-PET) and apparent diffusion coefficients (ADC) to conventional MRI improves diagnostic accuracy for distinguishing between PCNSL and GBM with similar MRI findings.We used conventional- and diffusion-weighted MRI and FDG-PET scans of 21 patients with histologically confirmed brain tumors exhibiting similar MRI findings (PCNSL, n = 14, GBM, n = 7) in our observer performance study that consisted of 3 interpretation sessions. ADC and maximum standard uptake values (SUVmax) of the tumors were calculated. Three radiologists first interpreted conventional MRI (1st session), then they read images to which the ADC value had been added (2nd session), and finally they interpreted images supplemented with SUVmax (3rd session). Observer performance was evaluated using κ statistic and receiver operating characteristics analyses.The addition of ADC values to conventional MRI failed to improve the differentiation between PCNSL and GBM. The addition of SUVmax at the third session improved the diagnostic accuracy of all 3 readers and resulted in higher interobserver agreement; mean accuracy was 95% (range 93–100%). In one observer the accuracy of tumor differentiation was significantly improved at the third compared to the second session (p = 0.017).In a selected group of PCNSL and GBM with similar MRI findings, the addition of quantitative FDG-PET to MRI may improve their differentiation. ADC measurement did not allow further discrimination.
Keywords: Brain tumors; PET; MRI

The purpose of the present study was to evaluate the clinical usefulness of the delayed post-therapeutic 131I scan in patients with well-differentiated thyroid cancer by comparing the early scanned images with the delayed images.A total of 81 patients (female:male = 67:14; age 52 ± 13 years) with well-differentiated thyroid cancer who underwent scans the third and tenth day after 131I treatment were included in this study. The therapeutic dose ranged from 3.7 GBq (100 mCi) to 7.4 GBq (200 mCi). The early and delayed scan images were visually analyzed and the thyroid remnant-to-background uptake ratio (RBR) and the lesion-to-background uptake ratio (LBR) of metastatic lesions were calculated.Of the 81 patients, 5 lesions (2 lung lesions, 2 cervical lymph node lesions, and one thyroid remnant) in 4 patients (5%) were additionally found on the delayed scans, which were not identified on the early scans. Of 8 patients with high serum thyroglobulin (Tg) and negative finding on the early scan, the delayed scan identified additional lesions in 3 patients (38%). Visual analysis scores significantly decreased for both thyroid remnants and metastatic lesions on the delayed scan (p < 0.001 for all). Diffuse hepatic uptake was visualized in 86% of all patients on the delayed scan, while only 6% of the patients on the early scan (p < 0.001). The RBRs of both scans were compared in 59 patients, and the LBRs were compared in 8 patients with 23 lesions. The mean RBR and LBR on the delayed scan (8.0 ± 7.6 and 5.4 ± 5.2, respectively) were significantly lower than those on the early scan (12.0 ± 10.8 and 10.8 ± 7.6, respectively; p = 0.02 and p = 0.001, respectively).The 131I-avid lesions on the early scan were more easily detected by visual analysis and had higher uptake ratios than those on the delayed scan. However, for patients with high serum Tg and negative finding on the early scan, the delayed scan was helpful in identifying additional 131I-avid lesions.
Keywords: Thyroid cancer; Iodine-131; Post-therapeutic scan

18F-FDG PET/CT in inflammatory pseudotumor of the colon causing intussusception by Ju-Hye Jeong; Ihn-Ho Cho; Eun-Jung Kong; Kyung-Ah Chun; Yong-Jin Kim; Jae-Hwang Kim (447-450).
Inflammatory pseudotumor is a rare benign lesion mimicking malignancy both clinically and radiologically. An accurate diagnosis is still difficult and is based on the histological examination. Since inflammatory pseudotumor is exceptionally rare in the colon, this unexpected lesion can be mistaken for malignancy. We report the first case of inflammatory pseudotumor in the colon that showed 18F-fluorodeoxyglucose (FDG) uptake and acted as the lead point causing colocolic intussusception.
Keywords: Plasma cell granuloma; Colon; Intussusception; Positron-emission tomography

Accumulation of F-18 FDG in the infected pulmonary cyst in a patient with hydatid disease by Zeynep Gozde Ozkan; Cuneyt Turkmen; Yasemin Sanli; Berker Ozkan; Serhan Tanju (451-453).
Echinococcosis is endemic in certain parts of the world, including Turkey. When the pulmonary cyst has characteristic features, it can be easily diagnosed, but when the appearance changes as a result of complications, the cyst may resemble a malignant lesion. We presented a complicated pulmonary hydatid disease patient who was referred to our department for PET–CT, after the detection of 2 lung lesions.
Keywords: Echinococcosis; Pulmonary hydatid disease; PET–CT