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

• 대한핵의학회:학술대회논문집
• /
• 2004.11a
• /
• pp.383.1-383.1
• /
• 2004

• The Korean Journal of Nuclear Medicine Technology
• /
• v.19 no.2
• /
• pp.74-80
• /
• 2015

Purpose Breast lymphoscintigraphy is an important technique to present for body surface precisely, which shows a lymph node metastasis of malignant tumors at an early stage and is performed before and after surgery in patients with breast cancer. In this study, we evaluated several methods of body outline imaging to present exact location of lesions, as well as compared respective exposure doses. Materials and Methods RANDO phantom and SYMBIA T-16 were used for obtaining imaging. A lesion and an injection site were created by inserting a point source of 0.11 MBq on the axillary sentinel lymph node and 37 MBq on the right breast, respectively. The first method for acquiring the image was used by drawing the body surface of phantom for 30 sec using $Na^{99m}TcO_4$ as a point source. The second, the image was acquired with $^{57}Co$ flood source for 30 seconds on the rear side and the left side of the phantom, the image as the third method was obtained using a syringe filled with 37 MBq of $Na^{99m}TcO_4$ in 10 ml of saline, and as the fourth, we used a photon energy and scatter energy of $^{99m}Tc$ emitting from phantom without any addition radiation exposure. Finally, the image was fused the scout image and the basal image of SPECT/CT using MATLAB$^{(R)}$ program. Anterior and lateral images were acquired for 3 min, and radiation exposure was measured by the personal exposure dosimeter. We conducted preference of 10 images from nuclear medicine doctors by the survey. Results TBR values of anterior and right image in the first to fifth method were 334.9 and 117.2 ($1^{st}$), 266.1 and 124.4 ($2^{nd}$), 117.4 and 99.6 ($3^{rd}$), 3.2 and 7.6 ($4^{th}$), and 565.6 and 141.8 ($5^{th}$). And also exposure doses of these method were 2, 2, 2, 0, and $30{\mu}Sv$, respectively. Among five methods, the fifth method showed the highest TBR value as well as exposure dose, where as the fourth method showed the lowest TBR value and exposure dose. As a result, the last method ($5^{th}$) is the best method and the fourth method is the worst method in this study. Conclusion Scout method of SPECT/CT can be useful that provides the best values of TBR and the best score of survey result. Even though personal exposure dose when patients take scout of SPECT/CT was higher than another scan, it was slight level comparison to 1 mSv as the dose limit to non-radiation workers. If the scout is possible to less than 80 kV, exposure dose can be reduced, and also useful lesion localization provided.

• Nuclear Engineering and Technology
• /
• v.55 no.8
• /
• pp.2873-2878
• /
• 2023

The purpose of this study is to perform radiation monitoring by acquiring gamma images and real-time optical images for ^99mTc vial source using charge couple device (CCD) cameras equipped with the proposed compact gamma camera. The compact gamma camera measures 86×65×78.5 mm³ and weighs 934 g. It is equipped with a metal 3D printed diverging collimator manufactured in a 45 field of view (FOV) to detect the location of the source. The circuit's system uses system-on-chip (SoC) and field-programmable-gate-array (FPGA) to establish a good connection between hardware and software. In detection modules, the photodetector (multi-pixel photon counters) is tiled at 8×8 to expand the activation area and improve sensitivity. The gadolinium aluminium gallium garnet (GAGG) measuring 0.5×0.5×3.5 mm³ was arranged in 38×38 arrays. Intrinsic and extrinsic performance tests such as energy spectrum, uniformity, and system sensitivity for other radioisotopes, and sensitivity evaluation at edges within FOV were conducted. The compact gamma camera can be mounted on unmanned equipment such as drones and robots that require miniaturization and light weight, so a wide range of applications in various fields are possible.

• The Korean Journal of Nuclear Medicine
• /
• v.39 no.1
• /
• pp.34-43
• /
• 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
• /
• v.38 no.1
• /
• pp.85-98
• /
• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• Bulletin of the Korean Chemical Society
• /
• v.27 no.2
• /
• pp.243-250
• /
• 2006

Three novel potential metal ion chelating units have been synthesized and characterized: 5-hexylcarbamoyl-3,4-dihydroxythiophene-2-carboxylic acid methyl ester (5), 3-benzyloxy-4-hydroxythiophene-2,5-dicarboxylic acid bis-hexylamide (6), and 3,4-dihydroxythiophene-2,5-dicarboxylic acid bis-hexylamide (7). The crystal structure of 6 was obtained and suggests the presence of three distinct intramolecular hydrogen bonds, namely $[N_{amide}-H{\cdot}{\cdot}{\cdot}O]$ $[O-H{\cdot}{\cdot}{\cdot}O_{amide}]$ and $[N_{amide}-H{\cdot}{\cdot}{\cdot}S]$. Boron chelation with 5, 6 and 7 through the use of $BF_3, \;B(OH)_3 \;or \;B(OMe)_3$ was probed by $^1H$, $^{11}B$, and $^{13}C$ NMR spectroscopy. Technetium (I) chelation with 5, 6 and 7 was also studied via HPLC elutions using $[^{99m}Tc(CO)_3(OH_2)_3]^+$.

• Proceedings of the Korean Nuclear Society Conference
• /
• 2004.10a
• /
• pp.1257-1258
• /
• 2004

• Proceedings of the Korean Nuclear Society Conference
• /
• 2004.10a
• /
• pp.1261-1262
• /
• 2004

• The Korean Journal of Nuclear Medicine Technology
• /
• v.15 no.2
• /
• pp.76-82
• /
• 2011

Purpose: Lymphoscintigraphy is absolutely being used standard examination in lymphatic diagnosis, evaluation after treatment, and it is useful for lymphedema to plan therapy. In case of lymphoscintigraphy of lower-extremity lymphedema, it had an effect on results if patients had not pose same position on the examination of 1 min, 1 hour and 2 hours after injection. So we'll study the methods to improve confidence with minimized quantitative analysis errors by influence factors. Materials and Methods: Being used the Infinia of GE Co. we injected $^{99m}Tc$-phytate 37 MBq (1.0 mCi) 4 sylinges into 40 people's feet hypodermically from June to August 2010 in Samsung Medical Center. After we acquired images of fixed and unfixed condition, we confirmed the count values change by attenuation of soft tissue and bone according to different feet position. And we estimated 5 times increasing 2 cm of distance between $^{99m}Tc$ point source and detector each time to check counts difference according to distance change by different feet position. Finally, we compared 1 and 6 min lymphoscintigraphy images with same position to check the effect of quantitative analysis results owing to difference of amounts of movement of the $^{99m}Tc$-phytate in the lymphatic duct. Results: Percentage difference regarding error values showed minimum 2.7% and maximum 25.8% when comparing fixed and unfixed feet position of lymphoscintigraphy examination at 1 min after injection. And count values according to distance were 173,661 (2 cm), 172,095 (4 cm), 170,996 (6 cm), 167,677 (8 cm), 169,208 counts (10 cm) which distance was increased interval of 2 cm and basal value was mean 176,587 counts, and percentage difference values were not over 2.5% such as 1.27, 1.79, 2.04, 2.42, 2.35%. Also, Assessment results about amounts of movement in lymphatic duct within 6 min until scanning after injection showed minimum 0.15%, and maximum 2.3% which were amounts of movement. We can recognize that error values represent over 20% due to only attenuation of soft tissue and bone except for distance difference (2.42%) and amounts of movement in lymphatic duct (2.3%). Conclusion: It was show that if same patients posed different feet position on the examination of 1 min, 1 hour and 2 hours after injection in the lymphoscintigraphy which is evaluating lymphatic flow of patients with lymphedema and analyzing amount of intake by lymphatic system, maximum error value represented 25.8% due to attenuation of soft tissue and bone, and PASW (Predictive Analytics Software) showed that fixed and unfixed feet position was different each other. And difference of distance between detector and feet and change of count values by difference of examination beginning time after injection influence on quantitative analysis results partially. Therefore, we'll make an effort to fix feet position and make the most of fixing board in lymphoscintigraphy with quantitative analysis.