• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.9-15
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• 2006

Purpose: Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyroid disease. Materials and Methods: Total patients were 119 cases (Men 15, $48{\pm}13$ yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was stored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. Results: ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of malignant thyroid diseases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution of NIS expression, which was not correlated with that of primary lesion. Conclusion: In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

• The Korean Journal of Nuclear Medicine
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• v.35 no.1
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• pp.69-74
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• 2001

Purpose: $^{99m}Tc$-HMPAO is a radiopharmaceutical for imaging cerebral blood flow. HMPAO (RR, SS)-4.8-diaza-3,6,6,9-tetramethylundecan-2,10- dione bisoxime) has three stereoismers such as, meso-. d-, and l-HMPAO. Techentium complexes of meso-HMPAO and d,l-HMPAO are known to have different in vivo brain uptakes. In this study, enantiomers of HMPAO (d-HMPAO and l-HMPAO) were separated from d,l-HMPAO. These enantiomers were labeled with $^{99m}Tc$ and the biodistribution studies were performed in mice. Materials and Methods: An intermediate imine product was produced from 2,3-butanedione monooxime and 2,2-dimethyl-1,3-propanediamine (54% yield) and was reduced into a mixture of three isomers (35% yield). The meso-isomer was separated from d,l-mixture by repeated fractional crystallization (11 % yield). The d- and l-enantiomers were subsequently separated by co-crystallization with optical isomers of tartaric acid (25% and 5% yield. respectively). Each enantiomeric HMPAO was labeled with $^{99m}Tc$ by reacting with $SnCI_2{\cdot}2H_2O\;and\;^{99m}Tc$-pertechnetate. Biodistribution study was performed 1 hr after tail vein injection to ICR mice. Results: Radiochemical purities of each compound were over 80%. In biodistribution study. the brain uptakes of d,l- d- and l-form were 1.34, 1.12 and 1.67% ID/g, respectively. In case of l-lsomer the brain uptake was higher (1.5 fold) than d-isomer. Conclusion: We successfully purified each enantiomeric HMPAO. In biodistribution study of stereoismers of $^{99m}Tc$-HMPAO in mice, l-HMPAO may show better brain image than d,l-HMPAO which was supplied in a commercial kit.

• The Korean Journal of Nuclear Medicine
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• v.35 no.1
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• pp.75-80
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• 2001

Purpose: There was little evidence that Tc-99m labeled ciprofloxacin (Infecton) located inside of bacteria. Antimicrobial activity of Infecton could be an indirect evidence of its location. We compared in vitro antimicrobial activities of Infecton and ciprofloxacin. Materials and methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Infecton and ciprofloxacin against three standard strains of bacteria, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were measured using modified broth macrodilution techniques and pour plate methods, respectively. Data were expressed as mean${\pm}$SE (range). Results: MICs of Infecton and ciprofloxacin were $1.12{\pm}0.20\;(0.8{\sim}1.6){\mu}g/ml\;and\;0.35{\pm}0.04\;(0.2{\sim}0.4){\mu}g/ml$ for S. aureus, $0.03{\pm}0.005\;(0.025{\sim}0.05){\mu}g/ml\;and\;0.011{\pm}0.001\;(0.006{\sim}0.012){\mu}g/ml$ for E. coil, and $0.96{\pm}0.16\;(0.8{\sim}1.6){\mu}g/ml)\;and\;0.56{\pm}0.098\;(0.4{\sim}0.8){\mu}g/ml$ for P. aeruginosa, respectively. MBCs of Infecton and ciprofloxacin were $2.56{\pm}0.39\;(1.6{\sim}3.2){\mu}g/ml\;and\;0.88{\pm}0.2\;(0.4{\sim}1.6){\mu}g/ml$ for S. aureus, $0.04{\pm}0.05\;(0.025{\pm}0.05){\mu}g/ml\;and\;0.02{\pm}0.01\;(0.025{\sim}0.05)\;{\sim}g/ml$ for E coli, and $2.24{\pm}0.39\;(1.6{\sim}3.2){\mu}g/ml\;and\;1.44{\pm}0.16\;(0.8{\sim}1.6){\mu}g/ml$ for P. aeruginosa, respectively. Conclusion: Although both MICs and UBCs of Infecton were higher than those of ciprofloxacin, all three standard bacterial strains were sensitive to Infecton. It could be an indirect evidence that Tc-99m Infecton be a specific imaging agent for bacterial infection.

• The Korean Journal of Nuclear Medicine
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• v.34 no.1
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• pp.82-93
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• 2000

Purpose: We characterized the signals obtained from the components of a small gamma camera using Nal(Tl)-position sensitive photomultiplier tube (PSPMT) and optimized the parameters employed in the modules of the system. Materials and Methods: The small gamma camera system consists of a Nal(Tl) crystal ($60{\times}60{\times}6mm^3$) coupled with a Hamamatsu R3941 PSPMT, a resister chain circuit, preamplifiers, nuclear instrument modules (NIMs), an analog to digital converter and a personal computer for control and display. The PSPMT was read out using a resistive charge division circuit which multiplexes the 34 cross wire anode channels into 4 signals (X+, X-, Y+, Y -). Those signals were individually amplified by four preamplifiers and then, shaped and amplified by amplifiers. The signals were discriminated and digitized via triggering signal and used to localize the position of an event by applying the Anger logic. The gamma camera control and image display was performed by a program implemented using a graphic software. Results: The characteristics of signal and the parameters employed in each module of the system were presented. The intrinsic sensitivity of the system was approximately $8{\times}10^3$ counts/sec/${\mu}Ci$. The intrinsic energy resolution of the system was 18% FWHM at 140 keV. The spatial resolution obtained using a line-slit mask and $^{99m}Tc$ point source were, respectively, 2.2 and 2.3 mm FWHM in X and Y directions. Breast phantom containing $2{\sim}7mm$ diameter spheres was successfully imaged with a parallel hole collimator. The image displayed accurate size and activity distribution over the imaging field of view Conclusion: We proposed a simple method for development of a small gamma camera and presented the characteristics of the signals from the system and the optimized parameters used in the modules of the small gamma camera.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.16-22
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• 2006

Purpose: Malignant Mixed Mullerian Tumor (MMMT) of the uterine corpus is one of the very uncommon and the most lethal tumors in the uterus. The aim of this study was to evaluate the role of FDG PET in detecting distant metastasis and residual and/or recurrent disease. Methods: Ten patients who underwent FDG PET for detecting distant metastasis and recurrence were included. focal FDG accumulation was regarded as abnormal. We also reviewed serum CA 125 levels, anatomical images, and histopathoiogical examination. Results: Three patients of 10 FDG PET showed abnormal FDG uptake. One had high serum CA 125 levels and high fractions of carcinomatous element on histopathologic examination. FDG PET showed metastatic lesions in unexpected locations, which could not be detected by anatomical images. Another had normal serum CA 125 levels with high sarcomatous element and CT could only detect a few lesions. The other had high serum CA 125 levels and also had high carcinomatous element. Seven patients who had no abnormal uptake on FDG PET had no clinical evidence of recurrence during the follow up period ($51.7{\pm}12.2$ months). The mean disease free intervals of these 7 patients were $36.4{\pm}6.0$ months. Two patients with abnormal findings had never become disease-free condition during the follow up period ($6.0{\pm}4.2$ months. Conclusion: FDG PET could be a useful modality for unexpected distant metastasis and follow up tool in patients with MMMT.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.201-208
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• 2007

Purpose: We investigated whether the diagnostic performance of SPECT scintimammography (SMM) can be improved by adding computer-aided diagnosis (CAD) of ultrasonography (US). Materials and methods: We reviewed breast SPECT SMM images and corresponding US images from 40 patients with breast masses (21 malignant and 19 benign tumors). The quantitative data of SPECT SMM were obtained as the uptake ratio of lesion to contralateral normal breast. The morphologic features of the breast lesions on US were extracted and quantitated using the automated CAD software program. The diagnostic performance of SPECT SMM and CAD of US alone was determined using receiver operating characteristic (ROC) curve analysis. The best discriminating parameter (D-value) combining SPECT SMM and the CAD of US was created. The sensitivity, specificity and accuracy of combined two diagnostic modalities were compared to those of a single one. Results: Both SPECT SMM and CAD of US showed a relatively good diagnostic performance (area under curve = 0.846 and 0.831, respectively). Combining the results of SPECT SMM and CAD of US resulted in improved diagnostic performance (area under curve =0.860), but there was no statistical differerence in sensitivity, specificity and accuracy between the combined method and a single modality. Conclusion: It seems that combining the results of SPECT SMM and CAD of breast US do not significantly improve the diagnostic performance for diagnosis of breast cancer, compared with that of SPECT SMM alone. However, SPECT SMM and CAD of US may complement each other in differential diagnosis of breast cancer.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.209-217
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• 2007

Purpose: Multidrug resistance (MDR) of the cancer cells related to mdr1 gene expression can be effectively treated by selective short hairpin RNA for mdr1 gene (shMDR). Sodium/iodide symporter (NIS) gene is well known to have both reporter and therapeutic gene characteristics. We have co-transfected both shMDR and NIS gene into colon cancer cells (HCT15 cell) expressing MDR and Tc-99m sestamibi and I-125 uptake were measured. In addition, cytotoxic effects of doxorubicin and I-131 therapy were also assessed after transfection. Material and Methods: At first, shMDR was transfected with liposome reagent into human embryonic kidney cells (HEK293) and HCT cells. shMDR transfection was confirmed by RT-PCR and western blot analysis. Adenovirus expressing NIS (Ad-NIS) gene and shMDR (Ad-shMDR) were co-transfected with Ad-NIS into HCT15 cells. Forty-eight hours after infection, inhibition of P-gycoprotein (Pgp) function by shMDR was analyzed by a change of Tc-99m sestamibi uptake and doxorubicin cytotoxicity, and functional activity of induced NIS gene expression was assessed with I-125 uptake assay. Results: In HEK293 cells transfected with shMDR, mdr1 mRNA and Pgp protein expressions were down regulated. HCT15 cells infected with 20 MOI of Ad-NIS was higher NIS protein expression than control cells. After transfection of 300 MOI of Ad-shMDR either with or without 10 MOI of Ad-NIS, uptake of Tc-99m sestamibi increased up to 1.5-fold than control cells. HCT15 cells infected with 10 MOI of Ad-NIS showed approximately 25-fold higher I-125 uptake than control cells. Cotransfection of Ad-shMDR and Ad-NIS resulted in enhanced cytotoxic by doxorubicin in HCT15 cells. I-131 treatment on HCT15 cells infected with 20 MOI of Ad-NIS revealed increased cytotoxic effect. Conclusion: Suppression of mdr1 gene expression, retention of Tc-99m sestamibi, enhanced doxorubicin cytotoxicity and increases in I-125 uptake were achieved in MDR expressing cancer cell by co-transfection of shMDR and NIS gene. Dual therapy with doxorubicin and radioiodine after cotransfection shMDR and NIS gene can be used to overcome MDR.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.6
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• pp.435-443
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• 2008

Purpose: Gated myocardial perfusion SPECT provides not only myocardial perfusion status but also various functional parameters of left ventricle. We compared left ventricular ejection fraction, end-diastolic volume, LV mass by cardiac SPECT using Quantitative Gated SPECT (QGS), 4D-MSPECT software and standard 2D-echocardiography. Materials and Methods: One hundred fourteen patients (male 51, female 63; 29-85 years old, mean $61.3\;{\pm}\;13.3$ years old) with normal perfusion status on Tc-99m tetrofosmin gated myocardial perfusion SPECT were analyzed retrospectively. Ejection fraction (LVEF), End-diastolic volume (LVED), LV mass (LVM) were calculated using QGS, 4D-MSPECT, and LVEF, LVM using 2D-echocardiography. Statistical analysis including Bland-Altman plot was performed using $MedCalc^{(R)}$ (MedCalc software, Mariakerke, Belgium). Results: The correlation of LVEF between methods was good: 0.95/0.96 (stress/rest) between QGS and 4D-MSPECT, 0.79 between QGS and echocardiography, 0.79 between 4D-MSPECT and echocardiography (p<0.001). Using Bland-Altman plot, the 95% confidence interval of agreement between QGS and 4D-MSPECT ranged from -12.7% to 7.3% / from -12.2% to 6.5% (stress/rest). The agreement between QGS and echocardiography, 4D-MSPECT and echocardiography ranged from -17.4% to 24.0%, and -14.8% to 27.0% respectively. The correlation of LVM between methods was also good: 0.95 between QGS and 4D-MSPECT, 0.76 between QGS and echocardiography, 0.73 between 4D-MSPECT and echocardiography (p<0.001). The 95% confidence interval of agreement between QGS and 4D-MSPECT ranged from -33.8g to 14.1g (stress/rest), The 95% confidence interval of agreement between QGS and echocardiography, 4D-MSPECT and echocardiography ranged from -148.7 g to 21.8. g, and -142.8 g to 35.5 g, respectively. Conclusion: There was a good correlation for LVEF, LVEO, LVM among methods (QGS, 4D-MSPECT, echocardiography), but the variance between methods was big. Therefore, the functional parameters by each method cannot be used interchangeably.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.6
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• pp.464-468
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• 2008

Purpose: Effective half life of I-131 ($T_{eff}$) in patients with differentiated thyroid cancer treated by I-131 is must-know value for dose calculation and determination of release time from isolation room. There has been no report about $T_{eff}$ in Koreans. Thus, author tried to measure dose rate without radiation exposure to faculty members and calculated $T_{eff}$. Methods: Probe of radiation survey meter was fixed at the wall of isolation room, and body of survey meter was placed outside the room. With this simple arrangement, author could measure radiation frequently without radiation exposure to faculty members in 68 patient (F=55, M=13, age=$47{\pm}13.7$) treated by I-131 ($3.7{\sim}7.4\;GBq$) for differentiated thyroid cancer from Jan 2006 to Dec 2006. From this data, $T_{eff}$, 48 hr retention rate, and the time necessary to whole body retention of I-131 become less than 1.1 GBq were calculated. Serum creatinine levels were measured before and after thyroid hormone withdrawal. Results: $T_{eff}$ was $15.4{\pm}4.3\;hr$ ($9.4{\sim}32.5\;hr$). There was a loose correlation between $T_{eff}$ and serum creatinine concentration (r=0.45). 48hr retention was $4.9{\pm}4.2%$ ($1{\sim}23%$). Time necessary to whole body retention of I-131 become less than 1.1 GBq was calculated as $47.1{\pm}13.2\;hr$ for 9.25 GBq, $42.1{\pm}11.9\;hr$ for 7.4 GBq, $35.7{\pm}10.0\;hr$ for 5.55 GBq, and $26.7{\pm}7.5\;hr$ for 3.7 GBq dose of I-131. Conclusion: Author successfully measured radiation dose rates in isolated patients treated by high dose of I-131 without radiation exposure to the faculty members with simple arrangement of survey meter probe. Using those data, $T_{eff}$ and some other indices were calculated.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.6
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• pp.444-450
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• 2008

Purpose: The aim of this study was to evaluate the usefulness of whole body positron emission tomography (PET) using $^{18}F-fluorodeoxyglucose$ ($^{18}F-FDG$) for cancer screening in asymptomatic subjects. Materials and Methods: The subjects were 1,762 men and 259 women who voluntarily underwent $^{18}F-FDG$ PET for cancer screening as a part of a routine health examination. Final diagnosis was decided by other diagnostic studies, pathological results or clinical follow-up for 1 year. Results: Of 2,021 subjects, 40 (2.0%) were finally proved to have cancer. Abnormal focal $^{18}F-FDG$ uptake suggesting malignancy was found in 102 subjects (5.0%). Among them, 21 subjects (1.0%) were proved to have cancer. Other tests in the routine health examination could not find 9 of 21 cancers (42.9%) detected by PET. The sensitivity, specificity, positive predictive value, and negative predictive value of PET for cancer screening were 52.5%, 95.9%, 20.6%, and 99.0%, respectively. Pathologies of cancers missed on PET were adenocarcinoma (n = 9; 3 colon cancers, 3 prostate cancers, 2 stomach cancers, and 1 rectal cancer), differentiated thyroid carcinoma (n = 6), bronchioalveolar cell carcinoma (n = 2), urinary bladder cancer (n = 1), and melanoma (n = 1). More than half of cancers which were not detected by PET were smaller than 1 cm in diameter. Conclusion: $^{18}F-FDG$ PET might be useful for cancer screening in asymptomatic subjects due to its high specificity and negative predictive value and playa supplementary role to the conventional health check-up, but it could not replace due to limited sensitivity for urological cancers, small-sized tumors and some hypometaboic cancers.