• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.382-392
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• 2003

Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.

• The Korean Journal of Nuclear Medicine
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• v.37 no.2
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• pp.83-93
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• 2003

Background: Lung-to-heart uptake ratio (LHR) in $^{201}Tl-chloride$ myocardial perfusion scan is believed to be a reliable marker for left ventricular (LV) dysfunction, but the clinical value of LHR is controversial for $^{99m}Tc-MIBI$ imaging. Furthermore, most of results suggesting lung uptake of $^{99m}Tc-MIBI$ as a potential marker for LV dysfunction used immediate post-stress images, instead of routine images acquired 1 hour after tracer injection. The goal of our study was to investigate whether LHR evaluated with routine gated $^{99m}Tc-MIBI$ imaging can reflect the degree of perfusion defect or left ventricular performance. Subjects and Methods: 241 patients underwent exercise $^{99m}Tc-MIBI$ myocardial SPECT were classified into normal myocardial perfusion (NP, n=135) and abnormal myocardial perfusion (AP, n=106) group according to the presence of perfusion defect. LHR was calculated from anterior projection image taken at 1-hour after injection. Two legions of interest (ROIs) were placed on left lung above LV and on myocardium showing the highest radioactivity. Subjects were classified by left ventricular ejection fraction (LVEF), as Gr-I: >50%, Gr-II: 36-50%, Gr-III: <36% and by summed stress score (SSS), as Gr-A: <4, Gr-B: 4-8, Gr-C: 9-13, Gr-D: >13, LHR was compared among these groups. Results: In NP group(n=135), LHR, were higher in men than women ($men:\;0.311{\pm}0.03,\;women:\;0.296{\pm}0.03,\;p<0.05$). Significant difference, in LHR were found between NP and AP groups both for men and women ($men:\;0.311{\pm}0.03\;vs\;.\;0.331{\pm}0.06,\;women:\;0.296{\pm}0.03\;vs.\;0.321{\pm}0.07.\;p<0.05$). There were weak negative correlation between LHR and LVEF (r=-0.342, p<0.05) and weak positive correlation between LHR and SSS (r=0.478, p<0.05) in men, but not in women (LVEF: r=-0.279, p=0.100, SSS: r=0.276, p=0.103). Increased LHR was defined when for more than mean + 2SD value ($men{\geq}0.38,\;women{\geq}0.37$) of the LHR of the subject with normal perfusion. Increased LHR were observed more frequently in subjects with lower LVEF (Gr-I: 11.1%, Gr-II: 27.0%, Gr-III: 35.4%, p<0.05) and higher SSS(Gr-A: 14.0%, Gr-B: 5.7%, Gr-C: 18.2%, Gr-D: 40.7%, p<0.05). Conclusions: LHRs obtained from routine $^{99m}Tc-MIBI$ gated SPECT images were weakly correlated with LVEF and perfusion defect. Although significant overlaps were observed between normal and abnormal perfusion group, LHRs could be used as an indirect marker of severe perfusion defect or reduced left ventricular function.

• The Korean Journal of Nuclear Medicine
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• v.37 no.2
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• pp.110-119
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• 2003

Purpose: Radioiodine (I-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age $50{\pm}11$ years) of papillary thyroid cancer. Among them 43 patients were treated with ${\Leq}7.4GBq$, while 15 patients with ${\geq}9.25GBq$. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up I-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were $13.3{\pm}1.9\;and\;13.8{\pm}2.1GBq$, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were $1.54{\pm}0.03\;and\;1.78{\pm}0.03Gy$ (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-dose group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose I-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.291-298
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• 2007

Purpose: To investigate the feasibility of TI-201 SPECT with intra coronary injection (lC-I) in the detection of viable myocardium, we have performed SPECT imaging after direct intracoronary injection of TI-201 and images were compared with those of stress-reinjection (Re-I) SPECT. Methods: Fourteen coronary artery disease patients (male 11, mean age 54 years) who had myocardial infarction or demonstrated left ventricular wall motion abnormality on echocardiography were enrolled. Three mCi of TI-201 was injected into both coronary arteries during angiography and images were acquired between 6- and 24-hour after injection. Reinjection imaging with 1 mCi of TI-201 was performed at 4-hour after adenosine stress imaging with 3 mCi of TI-201. Images were interpreted according to 4-grade visual scoring system (grade 0-3). Segments with mild to moderated uptake (${\leq}$grade 1), and upgraded more than one score with reinjection, and were defined as viable myocardium. Results: Image quality was poor in two cases with IC-I. Numbers of non-viable segments were 60 (23.8%) with IC-I, and 38 (15.1%) with Re-I, respectively. Overall agreement for perfusion grade per myocardial segment in each IC-I and Re-I was 76.5%. Overall agreement for viable segment between IC-I and Re-I was 90.5%. Only one out of 38 segments interpreted as non-viable with Re-I were interpretated as viable with IC-I. And 23 out of 214 segments interpreted as viable with Re-I were interpreted as non-viable with IC-I. Conclusion: Intracoronary TI-201 SPECT seemed to be not advantageous over stress-rest reinjection imaging in the assessment of myocardial viability, mainly due to low count statistics at 6-hour or 24-hour delayed time points. The feasibility of intracoronary TI- 201 SPECT is considered to be limited.

• The Korean Journal of Nuclear Medicine Technology
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• v.18 no.1
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• pp.76-81
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• 2014

Purpose: Diversity and the lachrymal duct deformities and the passage inside the nasal cavity except for anterior image such as epiphora happens during the test were able to express more precisely during the dacryoscintigraphy. Also, we thought about the necessity of a method to classify the passage into the naso-lachrymal duct from epiphora. Therefore, we are to find the validity of the method to obtain both oblique views except for anterior views. Materials and Methods: The targets of this research are 78 patients with epiphora due to the blockage at the lachrymal duct from January 2013 to August 2013. Average age was $56.96{\pm}13.36$. By using a micropipette, we dropped 1-2 drops of $^{99m}TcO4^-$ of 3.7 MBq (0.1 mCi) with $10{\mu}L$ of each drop into the inferior conjunctival fold, then we performed dynamic check for 20 minutes with 20 frames of each minute. In case of we checked the passage from both eyes to nasal cavity immediately after the dynamic check, we obtained oblique view immediately. If we didn't see the passage in either side of the orbit, we obtained oblique views of the orbit after checking the frontal film in 40 minutes. The instrument we used was Pin-hole Collimator with Gamma Camera(Siemens Orbiter, Hoffman Estates, IL, USA). Results: Among the 78 patients with dacryoscintigraphy, 35 patients were confirmed with passage into the nasal cavity from the anterior view. Among those 35 patients, 15 patients were confirmed with passage into the nasal cavity on both eyes, and it was able to observe better passage patterns through oblique view with a result of 8 on both eyes, 2 on left eye, and 1 on right eye. 20 patients had passage in left eye or right eye, among those patients 10 patients showed clear passage compared to the anterior view. 13 patients had possible passage, and 30 patients had no proof of motion of the tracer. To sum up, 21 patients (60%) among 35 patients showed clear pattern of passage with additional oblique views compared to anterior view. People responded obtaining oblique views though 5 points scale about the utility of passage identification helps make diagnoses the passage, passage delayed, and blockage of naso-lachrymal duct by showing the well-seen portions from anterior view. Also, when classifying passage to naso-lachrymal duct and flow to the skin, oblique views has higher chance of classification in case of epiphora (anterior:$4.14{\pm}0.3$, oblique:$4.55{\pm}0.4$). Conclusion: It is considered that if you obtain oblique views of the bilateral orbits in addition to anterior view during the dacryoscintigraphy, the ability of diagnose for reading will become higher because you will be able to see the areas that you could not observe from the anterior view so that you can see if it emitted after the naso-lachrymal duct and the flow of epiphora on the skin.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.34-43
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• 2005

Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.

• The Korean Journal of Nuclear Medicine
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• v.36 no.4
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• pp.244-254
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• 2002

Purpose: This study investigated the differences between technetium-99m ethyl cysteinate dimer (Tc-99m ECD) and technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) uptake in the normal brain by means of statistical parametric mapping (SPM) analysis. Materials and Methods: We retrospectively analyzed age and sex matched 53 cases of normal brain SPECT. Thirty-two cases were obtained with Tc-99m ECD and 21 cases with Tc-99m HMPAO. There were no abnormal findings on brain MRIs. All of the SPECT images were spatially transformed to standard space, smoothed and globally normalized. The differences between the Tc-99m ECD and Tc-99m HMPAO SPECT images were statistically analyzed using statistical parametric mapping (SPM'99) software. The differences bgetween the two groups were considered significant ant a threshold of corrected P values less than 0.05. Results: SPM analysis revealed significantly different uptakes of Tc-99m ECD and Tc-99m HMPAO in the normal brains. On the Tc-99m ECD SPECT images, relatively higher uptake was observed in the frontal, parietal and occipital lobes, in the basal ganglia and thalamus, and in the superior region of the cerebellum. On the Tc-99m HMPAO SPECT images, relatively higher uptakes was observed in subcortical areas of the frontal region, temporal lobe, and posterior portion of inferior cerebellum. Conclusion: Uptake of Tc-99m ECD and Tc-99m HMPO in the normallooking brain was significantly different on SPM analysis. The selective use of Tc-99m ECD of Tc-99m HMPAO in brain SPECT imaging appears especially valuable for the interpretation of cerebral perfusion. Further investigation is necessary to determine which tracer is more accurate for diagnosing different clinical conditions.

• Applied Biological Chemistry
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• v.17 no.1
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• pp.1-30
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• 1974

Present study was undertaken to elucidate the relationship between uptake of nutrients and photosynthetic activities, and the translocation of several mineral nutrients in rice plants which were grown under different cultural conditions, utilizing radioactive tracer technique. Particular emphasis was placed on the analysis of patterns of nutrient uptake, the relationship between nutritional conditions and yield components. For this, rice plants grown on either low or high yielding fields at different growth stage were subjected to this study. The results are summarized as follows; 1. Varietal difference was observed in the uptake of potassium and phosphorus. Kusabue and Jinheung had good capacity but Paldal had rather poor capacity for the uptake of the both nutrients. 2. For rice plants, a high positive correlation was found between the oxidation of alpha plaus-naphthylamine by root and uptake of phosphorus. 3. Carbon assimilation rate repended on rice varieties. It was high in Noindo, Gutaenajuok #3 Suweon #82 and Jinheung but low in Taegujo, Kwanok, Yugu #132 etc. 4. Heavy application of nitrogen increased carbon assimilation in rice plants but this also depressed translocation of certain carbohydrates to ears. 5. Carbon assimilation wan greatly hampered in rice plants deficient in magnesium, phosphorus or potassium. 6. Total dry matter after ear formation stage, was much higher in rice plants grown in high yielding fields than those grown in low yielding fields. 7. Leaf area index(LAI) reached maximum at heading stage and decreased thereafter in high yielding fields. But in low yielding fields, it reached maximum before heading and sharply decreased thereafter due to early senescence of lower leaves. 8. In general, light transmission ratio (LTR) of leaves was higher in the early growth stage and lower in later stages. Higher ratio of LTR to leaf area index, was found in the rice grown in high yielding fields than those in low yielding fields. 9. Net photosynthetic activity decreased with the increase in leaf area index but was higher in high yielding fields than in low yielding fields. 10. After the ear formation stage, nitrogen, potassium and silicon as weil as $K_2O/N$ in straw were higher in high yielding fields than those in low yielding fields. 11. Nitrogen, phosphorus, potassium and magnesium taken up by rice plants in low yielding fields before heading stage were readily translocated to ears than those in high yielding fields. This suggests greater redistribution of nutrients in straw occurs due to lower uptake, in later growth stages, by rice plants grown in low yielding fields and hence results in early senescence due to nutrient deprivation. 12. In the high yielding fields nitrogen uptake by rice was slow but continuous throughout the life of the plants resulting in a large uptake even after heading. But, in low yielding fields the uptake was fast before heading and slow after heading. 13. A high positive correlation was found between the contents of nitrogen and potassium in the straw at heading stage and grain yield. Positive correlation was also found to hold between the contents of potassium, silicon, $K_2O/N$, $SiO_2/N$ in the straw at harvesting stage, and grain yield. 14. Carbon assimilation was greately hampered in rice plants deficient in magensium, phosphorus or potassium. 15. Uptake of nitrogen, phosphorus, potassium, silicon and manganese by rice was considerably higher in high yielding fields and reached maximum at ear formation stage. 16. In rice, a high positive correlation was discovered between total uptake of nitrogen, phosphorus, potassium, calcium, magnesium, silicon, manganese at harvesting stage and grain yield. 17. In rice, a high positive correlation was found between the total uptake of nitrogen, phosphorus, potassium, calcium, magnesium, silicon at harvesting stage, and number of spikelets per $3.3\;m^2$. In addition, a correlation was found between the total uptake of nitrogen and potassium and number of panicles per hill.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.30-41
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• 2007

Purpose: Bone metastasis in breast cancer patients are usually assessed by conventional Tc-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with $^{18}F-2-deoxyglucose$ (FDG-PET) can offer superior spatial resolution and improved specificity. FDG-PET/CT can offer more information to assess bone metastasis than PET alone, by giving a anatomical information of non-enhanced CT image. We attempted to evaluate the usefulness of FDG-PET/CT for detecting bone metastasis in breast cancer and to compare FDG-PET/CT results with bone scan findings. Materials and Methods: The study group comprised 157 women patients (range: $28{\sim}78$ years old, $mean{\pm}SD=49.5{\pm}8.5$) with biopsy-proven breast cancer who underwent bone scan and FDG-PET/CT within 1 week interval. The final diagnosis of bone metastasis was established by histopathological findings, radiological correlation, or clinical follow-up. Bone scan was acquired over 4 hours after administration of 740 MBq Tc-99m MDP. Bone scan image was interpreted as normal, low, intermediate or high probability for osseous metastasis. FDG PET/CT was performed after 6 hours fasting. 370 MBq F-18 FDG was administered intravenously 1 hour before imaging. PET data was obtained by 3D mode and CT data, used as transmission correction database, was acquired during shallow respiration. PET images were evaluated by visual interpretation, and quantification of FDG accumulation in bone lesion was performed by maximal SUV(SUVmax) and relative SUV(SUVrel). Results: Six patients(4.4%) showed metastatic bone lesions. Four(66.6%) of 6 patients with osseous metastasis was detected by bone scan and all 6 patients(100%) were detected by PET/CT. A total of 135 bone lesions found on either FDG-PET or bone scan were consist of 108 osseous metastatic lesion and 27 benign bone lesions. Osseous metastatic lesion had higher SUVmax and SUVrel compared to benign bone lesion($4.79{\pm}3.32$ vs $1.45{\pm}0.44$, p=0.000, $3.08{\pm}2.85$ vs $0.30{\pm}0.43$, p=0.000). Among 108 osseous metastatic lesions, 76 lesions showed as abnormal uptake on bone scan, and 76 lesions also showed as increased FDG uptake on PET/CT scan. There was good agreement between FDG uptake and abnormal bone scan finding (Kendall tau-b : 0.689, p=0.000). Lesion showed increased bone tracer uptake had higher SUVmax and SUVrel compared to lesion showed no abnormal bone scan finding ($6.03{\pm}3.12$ vs $1.09{\pm}1.49$, p=0.000, $4.76{\pm}3.31$ vs $1.29{\pm}0.92$, p=0.000). The order of frequency of osseous metastatic site was vertebra, pelvis, rib, skull, sternum, scapula, femur, clavicle, and humerus. Metastatic lesion on skull had highest SUVmax and metastatic lesion on rib had highest SUVrel. Osteosclerotic metastatic lesion had lowest SUVmax and SUVrel. Conclusion: These results suggest that FDG-PET/CT is more sensitive to detect breast cancer patients with osseous metastasis. CT scan must be reviewed cautiously skeleton with bone window, because osteosclerotic metastatic lesion did not showed abnormal FDG accumulation frequently.