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Annals of Nuclear Medicine (v.26, #9)

Somatostatin receptor scintigraphy with ¹¹¹In-octreotide in pulmonary carcinoid tumours correlated with pathological and ¹⁸FDG PET/CT findings by Serkan Kuyumcu; Isik Adalet; Yasemin Sanli; Cuneyt Turkmen; Zeynep Gozde Ozkan; Dilek Yilmazbayhan (pp. 689-697).

Pulmonary carcinoid (PC) tumors are rare neoplasms of the lung with good prognosis but diagnosis may be demanding since there is no exclusive modality alone to clearly differentiate a PC tumor. The purpose of this study is to establish the diagnostic features of somatostatin receptor scintigraphy (SRS), comparatively (where available) with ¹⁸FDG PET/CT (PET/CT) correlated with histopathologic findings.Twenty-one patients who underwent SRS with ¹¹¹In-octreotide and were diagnosed as having PC tumors were retrospectively studied. Thirteen patients were performed PET/CT. Primary tumour size, Ki-67 indexes, image analysis data of SRS and PET/CT including maximum standardized uptake values (SUVmax) together with false negative, false positive, true positive and true negative lesions were documented and discussed.Eleven (52.4 %) patients were typical (TC) and 10 (47.6 %) were atypical carcinoids (AC) with mean Ki-67 indexes of 2.1 and 24 %, respectively. Patients underwent SRS for solitary pulmonary nodule (SPN) characterization (n = 12) and determination of disease extension (n = 9). Overall sensitivity and specificity of SRS in the detection of primary tumour, lymph nodes (LN) and distant metastasis (DM) were 76 and 97 %, respectively, whereas, positive and negative predictive values were 95 and 86 %. PET/CT was performed for determining disease spread (n = 3) and metabolic characterization (n = 10) of SPNs. Mean SUVmax in the primary pulmonary lesion in TCs and ACs were 2.9 ± 0.8 and 7.9 ± 5.4, respectively. Nodal involvement (n = 5) and DM (n = 3) were also detected. Sensitivity and specificity of PET/CT in the detection of primary tumour, LNs and DM were 85 and 89.4 %, respectively.SRS is useful in the diagnosis and monitoring of PC tumors when incorporated with ¹⁸FDG PET/CT as a primary staging tool particularly in the determination of disease spread.

Keywords: Pulmonary carcinoid; Somatostatin receptor scintigraphy; FDG PET; Ki-67

Voxel-based comparison of preoperative FDG-PET between mesial temporal lobe epilepsy patients with and without postoperative seizure-free outcomes by Miwako Takahashi; Tsutomu Soma; Kensuke Kawai; Keitraro Koyama; Kuni Ohtomo; Toshimitsu Momose (pp. 698-706).

This study aims to elucidate differences in preoperative cerebral glucose metabolism between patients who did and did not become seizure free after unilateral mesial temporal lobe epilepsy (mTLE) surgery. We hypothesized that regional glucose metabolism on preoperative fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with seizure-free outcomes differed from that in patients who were not seizure free after appropriate epilepsy surgery for unilateral mTLE. In this study, we compared preoperative FDG-PET findings between these two patient groups by applying a statistical analysis approach, with a voxel-based Asymmetry index (AI), to improve sensitivity for the detection of hypometabolism.FDG-PET scans of 28 patients with medically refractory mTLE, of whom 17 achieved a seizure-free outcome (Engel class 1 a–b) during a postoperative follow-up period of at least 2 years, were analyzed retrospectively. Voxel values were adjusted by the AI method as well as the global normalization (GN) method. Two types of statistical analysis were performed. One was a voxel severity analysis with comparison of voxel values at the same coordinate, and the other was extent analysis with comparison of the number of significant voxels in the anatomical areas predefined with Talairach’s atlas.In the voxel severity analysis, significant hypometabolism restricted to the ipsilateral temporal tip and hippocampal area was detected in the postoperative seizure-free outcome group as compared to controls. No significant area was detected in the non-seizure-free group as compared to controls (family-wise error corrected, p < 0.05). With extent analysis using a low threshold, the extents of hypometabolism in the ipsilateral hippocampal, frontal and thalamic areas were larger in the seizure-free than in the non-seizure-free group (p = 0.01, 0.03 and 0.01, respectively.) On the other hand, in the contralateral frontal and thalamic areas, extents of hypometabolism were smaller in the seizure-free than in the non-seizure-free group (p = 0.01 and 0.01).We found the preoperative distribution of hypometabolism to differ between the two patient groups. Severe hypometabolism restricted to the unilateral temporal lobe, with ipsilateral dominant hypometabolism including mild decreases, may support the existence of an epileptogenic focus in the unilateral temporal lobe and a favorable seizure outcome after mTLE surgery.

Keywords: Asymmetry index; FDG-PET; Mesial temporal lobe epilepsy; Postoperative outcome

Intra-reader reliability of FDG PET volumetric tumor parameters: effects of primary tumor size and segmentation methods by B. Shah; N. Srivastava; A. E. Hirsch; G. Mercier; R. M. Subramaniam (pp. 707-714).

To establish the effects of size and segmentation methods on intra-reader reliability of primary tumor metabolic tumor volume (MTV) and total glycolytic activity (TGA) in human solid tumors.This is a retrospective study of 121 patients who had a baseline FDG PET/CT scan for oncologic staging. Volumetric parameter readings were performed in random order on two separate occasions, 12 weeks apart, by the same reader. The MTV and TGA were segmented using gradient and fixed maximum standardized uptake value (SUV_max) threshold methods. Intra-reader reliability was established by the intraclass correlation coefficient (ICC) and Bland–Altman analysis.The biases for MTV were 2.95, 14.76 and 11.13 % for gradient segmentation, 38 and 50 % SUV_max fixed threshold segmentations, respectively (p < 0.0001). For TGA, the corresponding biases were 0.76, 10.36 and 7.46 % (p < 0.0001). There were no statistically significant differences in the biases between the first and second reads for MTV segmented for small and large volume tumors by the gradient method (p < 0.34) or 50 % SUV_max threshold segmentation (p < 0.08). However, there were statistically significant differences in the corresponding biases for the 38 % SUV_max threshold segmentation (p < 0.04). There were no statistically significant differences in the biases between the first and second reads for TGA segmented for small and large volume tumors (p < 0.98).Intra-reader reliability for primary tumor FDG MTV and TGA is affected by the tumor size and segmentation methods. The segmentation bias was smaller for gradient method than percentage fixed threshold method for MTV. The segmentation biases were smaller for TGA than MTV.

Keywords: Metabolic tumor volume; Total glycolytic activity; Reader reliability

Effects of coverage extent and slice skipping on mean and maximum arterial ¹⁸F-FDG uptake ratios in patients with carotid plaque by Tae-Soo Noh; Jang Yoo; Se Won Kim; Eun Jeong Lee; Joon Young Choi; Byung-Tae Kim; Kyung-Han Lee (pp. 715-722).

To investigate the effects of variable measurement methods on mean and maximum SUV ratios of ¹⁸F-FDG uptake in carotid arteries. ¹⁸F-FDG PET/CT images of 74 subjects with carotid plaque were analyzed for mean and maximum target-to-background ratio (TBR) of uptake. Agreement was analyzed between TBR scores obtained using different vessel coverage and slice skipping.Mean TBR was increased by extending coverage from common carotid artery (CCA; 1.25) to carotid artery (CA; 1.33) and inclusion of ascending aorta (CA/AA; 1.34). Maximum TBR was increased from 1.47 to 1.54 and 1.61 by respective extensions. Both mean and maximum TBR were closely correlated between vessels. ICC and Kappa statistics revealed near perfect agreement between TBR obtained using every 2 or 3 segments and that without sipping. Bland–Altman plots showed bias by slice skipping to remain small, particularly for mean TBR. Finally, high correlations were displayed between mean and maximum TBR.Analysis of mean and maximum arterial ¹⁸F-FDG uptake in patients with carotid plaque is likely to benefit from extending coverage to segments above and below the CCA. The extra burden of measurement, in turn, can be lightened by skipping up to every 2 of 3 slices without compromising accuracy of results.

Keywords: PET/CT; ¹⁸F-FDG; Atherosclerosis; Carotid artery; Uptake ratio

Pre-therapeutic blood dosimetry in patients with differentiated thyroid carcinoma using 124-iodine: predicted blood doses correlate with changes in blood cell counts after radioiodine therapy and depend on modes of TSH stimulation and number of preceding radioiodine therapies by Verena Hartung-Knemeyer; James Nagarajah; Walter Jentzen; Marcus Ruhlmann; Lutz S. Freudenberg; Alexander R. Stahl; Andreas Bockisch; Sandra J. Rosenbaum-Krumme (pp. 723-729).

Pre-therapeutic blood dosimetry prior to a high-dose radioiodine therapy (RAIT) is recommended and a blood dose of 2 Gy is considered to be safe. In this study, changes in the blood cell count after radioiodine therapy of high risk differentiated thyroid carcinoma (DTC) were analyzed and compared with the results of the pre-therapeutic blood dosimetry using ¹²⁴I. Moreover, the influence of different modes of TSH stimulation and the number of preceding radioiodine therapies on the blood dose were assessed.198 patients with locally advanced or metastasized DTC received a pre-therapeutic blood dosimetry using ¹²⁴I. To analyze the influence of the modes of TSH stimulation and the number of preceding RAITs on blood dose subgroups were built as follows: patients with endogenous TSH stimulation versus patients with exogenous TSH stimulation and patients with no preceding RAIT versus patients with at least one preceding RAIT. In 124/198 patients subsequent RAIT was performed. In 73/124 patients, hemograms were performed from day 2 to 12 month after RAIT.There was no high-grade bone marrow toxicity (i.e. ≥grade 3) in patients receiving less than 2 Gy blood dose—independent of the therapeutic history. Within the first month after radioiodine therapy, there was an overall decrease in the white blood cell and platelet counts. The erythrocyte count was essentially stable. There was a correlation between cell count decrease and predicted blood doses (Spearman’s correlation coefficient >−0.6 each) for the white cell line and the platelets. With regard to the subgroups, the blood dose per administered ¹³¹I activity (BDpA) was significantly higher in patients with endogenous TSH stimulation (median 0.08 Gy/GBq) than in patients with exogenous TSH stimulation (0.06 Gy/GBq) and in patients with no previous RAIT (0.08 Gy/GBq) compared to patients who had previously undergone at least one RAIT (0.07 Gy/GBq).The range of BDpA among DTC patients is rather wide. Our results suggest that lower blood doses can be expected when using exogenous TSH stimulation and blood doses are generally higher at first RAIT compared to subsequent RAITs. Thus, we advise to make blood dosimetry standard praxis prior to a high-activity RAIT.

Keywords: Blood dosimetry; Changes in blood cell counts; Bone marrow toxicity; 124-I; Radioiodine therapy

The usefulness of F-18 fluorodeoxyglucose positron emission tomography/computed tomography in patients with Langerhans cell histiocytosis by Hong Je Lee; Byeong-Cheol Ahn; Sang-Woo Lee; Jaetae Lee (pp. 730-737).

Langerhans cell histiocytosis (LCH) has a wide spectrum of clinical manifestations, ranging from spontaneous resolution to rapid progression or death, with the risk of permanent consequences. F-18 FDG PET/CT has been used for assessment of LCH patients. However, its clinical implication has not been well elucidated, mainly due to very low incidence of LCH. The aim of this study was to evaluate the clinical usefulness of F-18 FDG PET/CT in LCH patients.A database of 12 patients (mean age 17.8 ± 17.9 years; 7 children, 5 adults) who were diagnosed histopathologically as LCH was retrospectively reviewed. Two patients underwent F-18 FDG PET/CT before and after therapy, 6 patients underwent only before therapy and 4 patients underwent only after therapy.Nine (75.0 %) and 3 patients (25.0 %) had single-system (single site and multiple sites) and multisystem involvements, respectively. Pretreatment SUV_max of patients with multisystem or multiple site involvement of a single-system was significantly higher than that of patients with single site involvement of a single-system (3.29 ± 2.52 vs. 1.63 ± 0.52, p = 0.025). One patient showed multisystem risk organs (lung and bone marrow) involvement. In 2 patients, F-18 FDG PET/CT detected additional active LCH lesions not identified on conventional imaging modalities. In follow-up F-18 FDG PET/CT scans, complete resolution was identified in 2 patients and reactivation in another 2 patients.Results of this study suggest that F-18 FDG PET/CT is useful for identification of active lesions, stratification of disease stages, monitoring of therapeutic response, and detection of reactivation in LCH patients.

Keywords: Langerhans cell histiocytosis; F-18 FDG; PET/CT; Clinical usefulness

Impact of Ga-68 DOTATOC PET/CT on the diagnosis and treatment of patients with multiple endocrine neoplasia by Vera Froeling; Florian Elgeti; Martin H. Maurer; Christian Scheurig-Muenkler; Alexander Beck; Thomas J. Kroencke; Ulrich-Frank Pape; Bernd Hamm; Winfried Brenner; Nils F. Schreiter (pp. 738-743).

To evaluate the impact of Ga-68 DOTATOC PET/CT on diagnosis and therapeutic management of patients with multiple endocrine neoplasia (MEN).We did 28 Ga-68 DOTATOC PET/CT in 21 MEN patients (10 female, 11 men; mean age 41.3 years). 109 lesions detected were classified into MEN-associated lesions [i.e., neuroendocrine tumors (NET)] and non-MEN-associated lesions for PET, CT, and PET/CT. The impact of Ga-68 DOTATOC PET/CT on diagnosis and therapeutic management of patients with MEN were assessed by the records of the interdisciplinary NET tumor board including histopathological findings, clinical and radiological follow-up.Ga-68 DOTATOC PET/CT had an impact on diagnosis and therapeutic management in 10/21 (47.6 %) MEN patients. For detecting NET lesions in MEN patients Ga-68 DOTATOC PET/CT reached a sensitivity/specificity of 91.7 %/93.5 %. There was a significant difference for the detection rate between Ga-68 DOTATOC PET/CT and CT alone (p < 0.001) both using contrast-agent (p = 0.002) or not (p < 0.001) and also a significant difference between contrast-enhanced (CE-) CT and non-CE-CT alone (p = 0.006).GA-68 DOTATOC PET/CT allows a high detection rate of NET lesions in the context of MEN-1 syndrome as well as influence therapeutic management in nearly up to half of the patients. GA-68 DOTATOC PET/CT should include a CE-CT to improve MEN-associated NET lesion detection.

Keywords: Ga-68 DOTATOC PET/CT; Multiple endocrine neoplasia; Therapeutic management

Adjuvant thyroid remnant ablation in patients with differentiated thyroid carcinoma confined to the thyroid: a comparison of ablation success with different activities of radioiodine (I-131) by Marin Prpic; Nina Dabelic; Josip Stanicic; Tomislav Jukic; Milan Milosevic; Zvonko Kusic (pp. 744-751).

To assess efficiency of various I-131 activities on thyroid remnant ablation in thyroid cancer patients. The significance of patients’ characteristics, pathologic features and levels of Tg were analyzed.This study included 259 consecutive differentiated thyroid cancer patients, with disease confined to the thyroid, treated with I-131 after total thyroidectomy. Patients were divided into the three groups: 80 patients receiving low [1110–1850 MBq (30–50 mCi)], 121 intermediate [2775 MBq (75 mCi)] and 58 high [3700 MBq (100 mCi)] postoperative I-131 activities. Six to eight months after the application of radioiodine, measurements of TSH, Tg, anti-Tg antibodies (in hypothyroid state) together with ultrasound exam and whole-body scintigraphy were performed.The ablation was significantly more effective (after the first application) in patients receiving 100 mCi of I-131—89.7 % than in patients receiving lower activities (P = 0.016). There was no significant difference in ablation rate between the 30–50 mCi (77.5 %) and 75 mCi (70.2 %) groups. In the group receiving 30–50 mCi, patients with solitary tumors had significantly higher ablation rate (P = 0.038). In patients receiving 75 mCi ablation rates were higher among older patients (P = 0.005), with infiltration of the single lobe (P = 0.005), and with solitary tumor (P = 0.012). The rates of successful ablation after the second application of I-131 (after 12–16 months) amounted to 96, 97 and 96 % in the 30–50, 75 and 100 mCi groups, respectively. The activity of I-131 and age were independent factors for thyroid ablation failure after the first application of I-131 (model of binary logistic regression).The results of remnant ablation were satisfactory with all activities applied. Although after the first application of I-131 the activity of 100 mCi is significantly more effective in thyroid ablation than the administration of 30–50 mCi and 75 mCi, the ablation rates between all the three groups are similar (almost equal) after the second application. Thus, the activity to be administered may depend on patients’ characteristics and a detailed consideration of the merits and demerits of each I-131 activity.

Keywords: I-131; Remnant ablation; Thyroid cancer; Predictive factors

Xanthogranulomatous gastritis mimicking malignant GIST on F-18 FDG PET by Tomoya Tsukada; Tatsuo Nakano; Takashi Miyata; Shozo Sasaki; Kotaro Higashi (pp. 752-756).

Xanthogranulomatous gastritis (XGG) is a rare inflammatory lesion of the stomach, with only 11 reported cases worldwide. Furthermore, reports on the use of detailed diagnostic imaging in XGG are not available. Herein, we describe a case of XGG with detailed diagnostic imaging mimicking malignant gastrointestinal stromal tumor (GIST) in light of the current literature. A 79-year-old woman who presented with epigastric pain was referred to our hospital. Upper gastrointestinal endoscopy revealed an elevated lesion similar to a submucosal tumor (SMT). F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed intense FDG uptake in the mass. Additional imaging studies revealed a malignant GIST, which was suspected of having infiltrated the left lobe of the liver. Open surgery was carried out, but tumorous lesions were not found. For exact histopathological diagnosis, partial resection of the thickening gastric wall was performed, and XGG was diagnosed. We conclude that benign conditions, including XGG, should be considered when intense FDG uptake in SMT is found.

Keywords: Xanthogranuloma; Stomach; FDG; PET

[¹⁸F]FLT-PET to predict pharmacodynamic and clinical response to cetuximab therapy in Ménétrier’s disease by Eliot T. McKinley; R. Adam Smith; Jarred P. Tanksley; Mary Kay Washington; Ronald Walker; Robert J. Coffey; H. Charles Manning (pp. 757-763).

Molecular imaging biomarkers of proliferation hold great promise for quantifying response to personalized medicine. One such approach utilizes the positron emission tomography (PET) tracer 3′-deoxy-3′[¹⁸F]-fluorothymidine ([¹⁸F]FLT), an investigational agent whose uptake reflects thymidine salvage-dependent DNA synthesis. The goal of this study was to evaluate [¹⁸F]FLT-PET in the setting of Ménétrier’s disease (MD), a rare, premalignant hyperproliferative disorder of the stomach treatable with cetuximab therapy. Over 15 months, a patient with confirmed MD underwent cetuximab therapy and was followed with sequential [¹⁸F]FLT-PET. For comparison to MD, an [¹⁸F]FLT-PET study was conducted in another patient to quantify uptake in a normal stomach. Prior to cetuximab therapy, stomach tissue in MD was easily visualized with [¹⁸F]FLT-PET, with pre-treatment uptake levels exceeding normal stomach uptake by approximately fourfold. Diminished [¹⁸F]FLT-PET in MD was observed following the initial and subsequent doses of cetuximab and correlated with clinical resolution of the disease. To our knowledge, this study reports the first clinical use of [¹⁸F]FLT-PET to assess proliferation in a premalignant disorder. We illustrate that the extent of MD involvement throughout the stomach could be easily visualized using [¹⁸F]FLT-PET, and that response to cetuximab could be followed quantitatively and non-invasively in sequential [¹⁸F]FLT-PET studies. Thus, [¹⁸F]FLT-PET appears to have potential to monitor response to treatment in this and potentially other hyperproliferative disorders.

Keywords: FLT; Proliferation; Treatment response; EGFR; Ménétrier’s disease

Role of ¹⁸F-FDG PET-CT for evaluating the response to reduced-intensity conditioning allogeneic transplant in heavily pre-treated patients with chronic lymphocytic leukemia: preliminary results in nine patients by Silvia Taralli; Maria Lucia Calcagni; Vittoria Rufini; Luca Laurenti; Simona Sica; Patrizia Chiusolo; Giuseppe Leone; Alessandro Giordano (pp. 764-768).

The aim of our preliminary study was to evaluate the potential role of ¹⁸F-FDG PET-CT in monitoring response to reduced-intensity conditioning (RIC) transplant in a small series of chronic lymphocytic leukemia (CLL) patients and to compare the results with those obtained by standard criteria.We retrospectively analyzed 9 consecutive refractory/relapsed CLL patients, who underwent RIC transplant from March 2004 until May 2009. PET-CT was planned at 6–8 months after transplant to assess response and at a mean of 6 months during follow-up. The mean long-term follow-up period was 38 months (range 12–74 months, median 29 months).The first PET-CT showed abnormal ¹⁸F-FDG uptake in five patients, while by standard criteria eight patients showed persistent disease. At the end of follow-up (mean 38 months), all four patients with previously negative scan were still PET negative and in complete remission by standard criteria. All five patients with previously positive scan were still PET positive: one patient died for disease progression and four are alive with disease.Our preliminary data, although in a small series of CLL patients, suggest that the metabolic findings revealed at first PET-CT after transplant seem to predict the patient outcome and to assess the metabolic disease status earlier than clinical evaluation by standard criteria. PET-CT performed during follow-up may be useful to early detect disease progression.

Keywords: PET-CT; Chronic Lymphocytic Leukemia; Non-myeloablative transplant

Erratum to: Novel method for quantitative evaluation of cardiac amyloidosis using ²⁰¹TlCl and ^99mTc-PYP SPECT by Yasushi Yamamoto; Masahisa Onoguchi; Masuo Haramoto; Nobuhiro Kodani; Akio Komatsu; Hajime Kitagaki; Kazuaki Tanabe (pp. 769-769).

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Annals of Nuclear Medicine (v.26, #9)