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Annals of Nuclear Medicine (v.26, #2)

Radioactive iodine (¹³¹I) therapy for differentiated thyroid cancer in Japan: current issues with historical review and future perspective by Tatsuya Higashi; Takashi Kudo; Seigo Kinuya (pp. 99-112).

Radioactive iodine (RAI, ¹³¹I) has been used as a therapeutic agent for differentiated thyroid cancer (DTC) with over 50 years of history. Recently, it is now attracting attention in medical fields as one of the molecular targeting therapies, which is known as targeted radionuclide therapy. Radioactive iodine therapy (RIT) for DTC, however, is now at stake in Japan, because Japan is confronting several problems, including the recent occurrence of the Great East Japan Disaster (GEJD) in March 2011. RIT for DTC is strictly limited in Japan and requires hospitalization. Because of strict regulations, severe lack of medical facilities for RIT has become one of the most important medical problems, which results in prolonged waiting time for Japanese patients with DTC, including those with distant metastasis, who wish to receive RIT immediately. This situation is also due to various other factors, such as prolonged economic recession, super-aging society, and subsequent rapidly changing medical environment. In addition, due to the experience of atomic bombings in Hiroshima and Nagasaki, Japanese people have strong feeling of “radiophobia”. There is fear that GEJD and related radiation contamination may worsen this feeling, which might be reflected in more severe regulation of RIT. To overcome these difficulties, it is essential to collect and disclose all information about the circumstances around this therapy in Japan. In this review, we would like to look at this therapy through several lenses, including historical, cultural, medical, and socio-economic points of view. We believe that clarifying the problems is sure to lead to the resolution of this complicated situation. We have also included several recommendations for future improvements.

Keywords: Radioactive iodine; Radioactive iodine therapy; Differentiated thyroid cancer; Fukushima; Radiophobia

A nuclear power plant accident in Fukushima: what should we do? by Seigo Kinuya (pp. 113-114).

PET scanning in plastic and reconstructive surgery by Liodaki Eirini; Liodakis Emmanouil; Papadopoulos Othonas; Machens Hans-Günther; Papadopulos A. Nikolaos (pp. 115-122).

In this report we highlight the use of PET scan in plastic and reconstructive surgery. PET scanning is a very important tool in plastic surgery oncology (melanoma, soft-tissue sarcomas and bone sarcomas, head and neck cancer, peripheral nerve sheath tumors of the extremities and breast cancer after breast esthetic surgery), as diagnosis, staging, treatment planning and follow-up of cancer patients is based on imaging. PET scanning seems also to be useful as a flap monitoring system as well as an infection’s imaging tool, for example in the management of diabetic foot ulcer. PET also contributes to the understanding of pathophysiology of keloids which remain a therapeutic challenge.

Keywords: PET; Plastic and reconstructive surgery; Skin cancer; Tumors in plastic surgery; Flap monitoring

PET scanning in plastic and reconstructive surgery by Liodaki Eirini; Liodakis Emmanouil; Papadopoulos Othonas; Machens Hans-Günther; Papadopulos A. Nikolaos (pp. 115-122).

Keywords: PET; Plastic and reconstructive surgery; Skin cancer; Tumors in plastic surgery; Flap monitoring

The interpolated projection data estimation method improves the image quality of myocardial perfusion SPECT with a short acquisition time by Kimie Asao; Akihiro Takaki; Mitsuhiro Tominaga; Masayuki Sasaki (pp. 123-130).

The interpolated projection data estimation processing (IPDE) method increases the amount of projection data by interpolation of the projection data. We examined the usefulness of the IPDE method for ²⁰¹Tl myocardial perfusion imaging (MPI) single photon emission computed tomography (SPECT) with a short acquisition time.Forty patients with suspected ischemic heart disease underwent stress ²⁰¹Tl-MPI SPECT. Both stress and delayed images were acquired with 4 cycles of 360° continuous rotation with a 90-direction setting for 14 min. The projection data used for reconstruction were 1) all cycle data (Tl-90-14min), 2) 2 cycles of data (Tl-90-7min), and 3) 2 cycles of data processed using the IPDE method (Tl-180IPDE-7min). This study compared the detection of the perfusion defect by the uptake score and the image quality of ²⁰¹Tl-MPI SPECT using the normalized mean square error (NMSE).The uptake score of Tl-180IPDE-7min was significantly more concordant with Tl-90-14min in comparison to the Tl-90-7min (p < 0.05). The NMSE of the Tl-180IPDE-7min (1.85 ± 1.06%) was significantly lower than that of the Tl-90-7min (2.07 ± 1.24%) (p < 0.05). The degree of improvement by the IPDE method was significantly greater for the delayed ²⁰¹Tl-MPI SPECT than for the stress ²⁰¹Tl-MPI SPECT (p < 0.05).The IPDE method improved the image quality and secured the diagnostic ability of ²⁰¹Tl-MPI SPECT for a short acquisition time. Furthermore, the IPDE method is a simple software program that does not require any expensive equipment or use advanced algorithms. These results suggest that the IPDE method may be useful as an adjunctive method for shortening the acquisition time of ²⁰¹Tl-MPI SPECT.

Keywords: Myocardial perfusion; SPECT; Interpolation; Short acquisition time; Reconstruction

Usefulness of breast-specific gamma imaging as an adjunct modality in breast cancer patients with dense breast: a comparative study with MRI by Bom Sahn Kim (pp. 131-137).

The aim of this study was to evaluate the adjunctive benefits of breast-specific gamma imaging (BSGI) versus magnetic resonance imaging (MRI) in breast cancer patients with dense breasts.This study included a total of 66 patients (44.1 ± 8.2 years) with dense breasts (breast density >50%) and already biopsy-confirmed breast cancer. All of the patients underwent BSGI and MRI as part of an adjunct modality before the initial therapy. Of 66 patients, the 97 undetermined breast lesions were newly detected and correlated with the biopsy results.Twenty-six of the 97 breast lesions proved to be malignant tumors (invasive ductal cancer, n = 16; ductal carcinoma in situ, n = 6; mixed or other malignancies, n = 4); the remaining 71 lesions were diagnosed as benign tumors. The sensitivity and specificity of BSGI were 88.8% (confidence interval (CI), 69.8–97.6%) and 90.1% (CI, 80.7–95.9%), respectively, while the sensitivity and specificity of MRI were 92.3% (CI, 74.9–99.1%) and 39.4% (CI, 28.0–51.7%), respectively (p < 0.0001). MRI detected 43 false-positive breast lesions, 37 (86.0%) of which were correctly diagnosed as benign lesions using BSGI. In 12 malignant lesions <1 cm, the sensitivities of BSGI and MR imaging were 83.3% (CI, 51.6–97.9%) and 91.7% (CI, 61.5–99.8%), respectively.BSGI showed an equivocal sensitivity and a high specificity compared to MRI in the diagnosis of breast lesions. In addition, BSGI had a good sensitivity in discriminating breast cancers ≤1 cm. The results of this study suggest that BSGI could play a crucial role as an adjunctive imaging modality which can be used to evaluate breast cancer patients with dense breasts.

Keywords: Breast cancer; Breast-specific gamma imaging; MRI; Dense breast; Tumor size

Evaluation of primary prostate cancer using ¹¹C-methionine-PET/CT and ¹⁸F-FDG-PET/CT by Masato Shiiba; Keiichi Ishihara; Go Kimura; Tomoyuki Kuwako; Naohisa Yoshihara; Hidetaka Sato; Yukihiro Kondo; Shin-ichi Tsuchiya; Shin-ichiro Kumita (pp. 138-145).

The objective of this study was to evaluate the capability of ¹¹C-methionine (MET)-PET/CT and ¹⁸F-2-deoxy-2-fluoro-d-glucose (FDG)-PET/CT to diagnose primary prostate cancer using recently developed Gemini TF PET/CT (Philips Healthcare, Cleveland, OH).Twenty men who had been referred for a diagnostic work-up for prostate cancer were enrolled in this study. MET- and FDG-PET/CT by high-resolution mode were carried out on the same day prior to prostate biopsy and each maximum standardized uptake value (SUVmax) was compared with the pathological findings. The regions of interest (about 100 mm² small round) were placed at standard 6 points of the peripheral zone and 4 points in the apex of the transitional zone in cases that had undergone biopsy of the internal gland. We summed two scores if a specimen had inhomogeneous Gleason scores (e.g. GS 7; 4 + 3) and doubled the score when the Gleason score was the same (e.g. GS 8; 4 × 2). We divided the tumors into three groups. If the summed Gleason score of the specimens was 5 or less, they were grouped as NG (no grade with the Gleason score). If the summed Gleason score was 6 or 7, the tumors were defined as LG (low Gleason score group), and if the summed Gleason score was 8, 9 or 10, the tumors were classified as HG (high Gleason score group). The mean SUVmax was calculated and one-way analysis of variance or Kruskal–Wallis test and the Tukey post hoc test were performed for statistical comparisons. The capabilities of MET and FDG for diagnosing prostate cancer were evaluated through analysis of the area under the curve of the receiver operating characteristic (ROC) curve. The cut-off levels of SUVmax for the highest accuracy were determined by the results of the ROC analysis, and the sensitivity, specificity and accuracy were calculated.The PET images, obtained with Gemini TF PET/CT, allowed visual identification of anatomical locations within the prostate gland. Among the mean SUVmax of MET, FDG early phase and FDG delayed phase, the differences between NG and HG were all statistically significant (P < 0.01). With MET the difference between NG and LG was also significant (P < 0.05). And for the elevation rate from FDG early to delayed phase, the difference between NG and HG was significant (P < 0.05). The cut-off SUVmax, sensitivity, specificity, accuracy for distinguishing between NG and LG + HG by MET, FDG early and delayed phase were 3.15/78.7/75.6/78.3, 2.81/61.7/80.0/70.7 and 3.00/62.8/78.9/70.7, respectively. And the same factors between NG + LG and HG were 3.76/70.1/89.7/82.6, 2.88/70.1/82.9/78.3 and 3.47/62.7/86.3/77.7, respectively.In terms of the capability to diagnose prostate cancer of high Gleason score (≥8), there was no significant difference between MET and FDG. MET appears to be useful for detecting prostate cancer of both low and high Gleason score.

Keywords: ¹¹C-Methionine; ¹⁸F-FDG-PET/CT; Time-of-flight PET; Prostate cancer

Erratum to: Evaluation of primary prostate cancer using ¹¹C-methionine-PET/CT and ¹⁸F-FDG-PET/CT by Masato Shiiba; Keiichi Ishihara; Go Kimura; Tomoyuki Kuwako; Hisashi Yoshihara; Hidetaka Sato; Yukihiro Kondo; Shin-ichi Tsuchiya; Shin-ichiro Kumita (pp. 146-146).

The agreement of left ventricular function parameters between ^99mTc-tetrofosmin gated myocardial SPECT and gated myocardial MRI by Yasuyoshi Kuroiwa; Shigeki Nagamachi; Tosiaki Miyati; Kennichirou Yamaguchi; Ryuichi Nishii; Noriyuki Kuga; Toshiya Azuma; Hideo Arita; Masaji Maeda; Shozo Tamura; Keiichi Kawai (pp. 147-163).

The aim is to compare and evaluate the agreement of quantification of left ventricular functional parameters obtained by two different methods, ^99mTc-tetrofosmin gated myocardial perfusion SPECT (MPS) and cardiac magnetic resonance imaging (CMR).Ten healthy male volunteers participated. Gated MPS data were acquired using 32 frames, which were also combined into 16- and 8-frame data set for the investigation. Gated CMR data were acquired using 8, 16 and 32-frame for the different sets. All examinations were conducted in resting and at exercise conditions. Quantitative measurements of end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR) and time to peak filling (TTPF) were done for each study, respectively. Finally, we evaluated the concordance of parameters between gated MPS and gated CMR by % difference and Bland–Altman plot analysis.LVEF showed favorable concordance in both rest and exercise conditions (% differences were around 10%). PER, PFR and TTPF also showed good concordances in rest conditions, under 32-frame gated collections particularly (% differences were around 10%). In exercise conditions, although the concordances were relatively good, certain variances were noted (% differences were around 20–25%). Regarding left ventricular volumes, the concordance were worse in both conditions (% differences were around 30–40%).In quantifying of left ventricular function parameter, gated CMR provides similar quantitative values comparing with gated MPS except for ventricular volumes in rest conditions. In contrast, there were certain variations except for LVEF in exercised examinations. When we follow patients by the same cardiac parameters with CMR and MPS, using parameters across the two modalities proved to be possible under rest condition. However, it is limited at exercise condition.

Keywords: Left ventricular function parameters; Gated MPS; Gated CMR; The agreement

Correlated regions of cerebral blood flow with clinical parameters in Parkinson’s disease; comparison using ‘Anatomy’ and ‘Talairach Daemon’ software by Hyun Jin Yoon; Sang Myung Cheon; Young Jin Jeong; Do-Young Kang (pp. 164-174).

We assign the anatomical names of functional activation regions in the brain, based on the probabilistic cyto-architectonic atlas by Anatomy 1.7 from an analysis of correlations between regional cerebral blood flow (rCBF) and clinical parameters of the non-demented Parkinson’s disease (PD) patients by SPM8. We evaluated Anatomy 1.7 of SPM toolbox compared to ‘Talairach Daemon’ (TD) Client 2.4.2 software.One hundred and thirty-six patients (mean age 60.0 ± 9.09 years; 73 women and 63 men) with non-demented PD were selected. Tc-99m-HMPAO brain single-photon emission computed tomography (SPECT) scans were performed on the patients using a two-head gamma-camera. We analyzed the brain image of PD patients by SPM8 and found the anatomical names of correlated regions of rCBF perfusion with the clinical parameters using TD Client 2.4.2 and Anatomy 1.7. The SPM8 provided a correlation coefficient between clinical parameters and cerebral hypoperfusion by a simple regression method. To the clinical parameters were added age, duration of disease, education period, Hoehn and Yahr (H&Y) stage and Korean mini-mental state examination (K-MMSE) score.Age was correlated with cerebral perfusion in the Brodmann area (BA) 6 and BA 3b assigned by Anatomy 1.7 and BA 6 and pyramis in gray matter by TD Client 2.4.2 with p < 0.001 uncorrected. Also, assigned significant correlated regions were found in the left and right lobules VI (Hem) with duration of disease, in left and right lobules VIIa crus I (Hem) with education, in left insula (Ig2), left and right lobules VI (Hem) with H&Y, and in BA 4a and 6 with K-MMSE score with p < 0.05 uncorrected by Anatomy 1.7, respectively. Most areas of correlation were overlapped by two different anatomical labeling methods, but some correlation areas were found with different names.Age was the most significantly correlated clinical parameter with rCBF. TD Client found the exact anatomical name by the peak intensity position of the cluster while Anatomy 1.7 of SPM8 toolbox, using the cyto-architectonic probability maps, assigned the anatomical name by percentage value of the probability.

Keywords: SPECT; Parkinson’s disease (PD); SPM8; Clinical parameters; Probabilistic cyto-architectonic maps

Usefulness of ¹⁸F-FDG uptake with clinicopathologic and immunohistochemical prognostic factors in breast cancer by Bom Sahn Kim; Sun Hee Sung (pp. 175-183).

The aim of this study was to analyze the clinical significance of maxSUV with clinicopathologic and immunohistochemical prognostic factors in patients with primary breast cancer.Ninety-one women (48.5 ± 11.2 years of age) with breast cancer who underwent ¹⁸F-FDG PET (PET) before surgery were recruited. All of the breast cancers were invasive ductal carcinomas and ≥1 cm in size to exclude a partial volume effect. The maxSUV of breast cancers was compared with histopathologic and immunohistochemical findings. Additionally, the ability of PET to discriminate axillary nodal status (ANS) and correlation between ANS and tumor characteristics were evaluated.A high maxSUV of breast cancer was significantly correlated with the following poor prognosis factors: tumor invasiveness >2 cm (2.9 vs. 5.4; p < 0.001); high score of nuclear (3.5 vs. 5.3; p = 0.008) or histologic grade (3.3 vs. 5.5; p < 0.001); MIB-1 ≥10% (3.0 vs. 4.9; p < 0.002); ER-negativity (4.8 vs. 3.8; p = 0.019); PR-negativity (5.0 vs. 3.6; p = 0.029); and triple negativity (ER-, PR-, and c-erbB-2-negative; 5.3 vs. 3.8; p < 0.016). MaxSUV was not affected by menopausal status, ANS, lymphovascular invasion, including CD34 and D2-40 (LVIs), p53, and c-erbB-2 status. Additionally, the sensitivity and specificity of PET for discriminating ANS were 51.1 and 97.8%, respectively. ANS was correlated with tumor invasiveness >2 cm (p = 0.046), LVIs (all of variables; p < 0.001), and triple negativity (p = 0.049).A high FDG uptake of breast tumor is correlated with several poor prognosis factors, such as tumor invasiveness >2 cm, higher tumor grade, higher MIB-1, hormonal receptor negativity, and triple negativity. However, PET has a limited value in discriminating axillary lymph nodes. Pre-operative PET is a useful modality to predict biologic poor prognosis factors which could affect adjunctive therapy of breast cancer.

Keywords: ¹⁸F-FDG; SUV; Breast cancer; Biologic markers; Axillary lymph node

Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 by Ayahisa Watanabe; Ken-ichi Nishijima; Songji Zhao; Yoshikazu Tanaka; Takeshi Itoh; Hiroshi Takemoto; Nagara Tamaki; Yuji Kuge (pp. 184-191).

Glycosylation is generally applicable as a strategy for increasing the activity of bioactive proteins. In this study, we examined the effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 (GLP-1) as a bioactive peptide for type 2 diabetes.Noninvasive imaging studies were performed using a gamma camera after the intravenous administration of ¹²³I-GLP-1 or ¹²³I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using ¹²⁵I-GLP-1 or ¹²⁵I-glycosylated GLP-1, organ samples were measured for radioactivity. Plasma samples were added to 15% trichloroacetic acid (TCA) to obtain TCA-insoluble and TCA-soluble fractions. The radioactivity in the TCA-insoluble and TCA-soluble fractions was measured.In the noninvasive imaging studies, a relatively high accumulation level of ¹²³I-GLP-1 was found in the liver, which is the major organ to eliminate exogenous GLP-1. The area under the time-activity curve (AUC) of ¹²³I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of ¹²³I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using ¹²⁵I-labeled peptides. The AUC of ¹²⁵I-glycosylated GLP-1 in the TCA-insoluble fraction was significantly higher (1.7-fold) than that of GLP-1.This study demonstrated that glycosylation significantly decreased the distribution of radiolabeled GLP-1 into the liver and increased the concentration of radiolabeled GLP-1 in plasma. These results suggested that glycosylation is a useful strategy for decreasing the distribution into the liver of bioactive peptides as desirable pharmaceuticals.

Keywords: Noninvasive imaging; Biodistribution; Glycosylation; Glucagon-like peptide 1

Use of an oral effervescent agent in the evaluation of gastric ⁶⁷Ga uptake by Takeshi Yamada; Yusuke Inoue; Yuji Asano; Yasumasa Nippashi; Reiko Woodhams; Keiji Matsunaga; Masao Tago (pp. 192-196).

Gastric uptake of ⁶⁷Ga may be observed in patients with no obvious gastric lesions, as well as those with gastric malignancy. The aim of this study was to investigate whether the use of an effervescent agent aids in evaluating gastric ⁶⁷Ga uptake.Twenty patients having or suspected of having gastric uptake on whole-body ⁶⁷Ga scintigrams were studied. Anterior abdominal images were obtained at baseline and after the oral intake of the effervescent agent (gas contrast image). The presence or absence of malignant gastric uptake was judged visually using the baseline image or gas contrast image. The judgment was compared with the clinical diagnosis, and the clinical usefulness of the gas contrast technique was assessed.In all patients, successful distension of the stomach was indicated in the gas contrast image. Clinical assessment showed gastric lesions in six patients (gastric involvement of lymphoma in 3, primary gastric lymphoma in 2, and adenocarcinoma in 1). The gas contrast image yielded accurate judgments of malignant gastric uptake in all patients except one with adenocarcinoma. Imaging after gastric distension induced by the oral effervescent agent contributed to excluding malignant gastric uptake in eight patients and demonstrating malignant gastric uptake in four patients.Benign gastric uptake may complicate the assessment of gastric lesions in ⁶⁷Ga scintigraphy. Additional spot imaging after oral intake of an effervescent agent can aid in evaluating malignant gastric lesions through gastric distension.

Keywords: ⁶⁷Ga citrate; Stomach; Neoplasm; Effervescent agent; Gastric distension

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Annals of Nuclear Medicine (v.26, #2)