The Prediction of HER2-Targeted Treatment Response Using 64CuTetra- Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report / 한국유방암학회지

A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent 64 Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status.64 Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions. Following trastuzumab emtansine treatment, there was a significant improvement in the lesions with 64 Cu-DOTA-trastuzumab accumulation. However, the lesions that did not accumulate 64 Cu-DOTA-trastuzumab aggravated. Therefore, it was concluded that 64 CuDOTA-trastuzumab PET/CT can be used to predict the outcome of HER2-targeted treatment by evaluating HER2 expression in breast cancer patients.

Age and Tumor Size is a Prognostic Factor in Pediatric/Adolescent Differentiated Thyroid Carcinoma / 대한두경부종양학회지

Background/Objectives@#To analyze the clinical characteristics of differentiated thyroid cancer (DTC) in children and adolescents.Materials & Methods: Medical records of 31 DTC cases that were diagnosed and treated at Korea Cancer Center Hospital between 2002 and 2018 were retrospectively reviewed. @*Results@#Most cases were papillary carcinoma (n=26), with female predominance (n=25). Median age was 16.4 years (range, 11.9-18.6 years). Extrathyroidal extension was present in 24 cases. Twenty cases had tumor involvement at cervical lymph nodes and three had lung metastasis. Twenty-two patients received radioactive iodide treatment with a median cumulative dose of 300 mCi (range, 100-920 mCi). During a median follow-up of 68.2 months (range, 2.3-191.4 months), serum thyroglobulin level was elevated in 15 patients. Among them, two cases had remnant thyroid tissue, 4 had recurrence at cervical lymph nodes, and the remaining 9 did not have any detectable lesion. All were alive, and 5-year event-free survival (EFS) was 45.2±10.1%. Age £15 years, tumor size, lymph node status (N1b), and distant metastasis had negative effects on EFS. On multivariate analysis, age and tumor size had prognostic significance. @*Conclusion@#For DTC of children and adolescents (£18 years old), age ≤15 years and tumor size were prognostic factor. Therefore, patients in this age group need meticulous follow-up. Further studies are necessary to answer the potential influence of age on the incidence and behavior of DTC.

Age and Tumor Size is a Prognostic Factor in Pediatric/Adolescent Differentiated Thyroid Carcinoma / 대한두경부종양학회지

Background/Objectives@#To analyze the clinical characteristics of differentiated thyroid cancer (DTC) in children and adolescents.Materials & Methods: Medical records of 31 DTC cases that were diagnosed and treated at Korea Cancer Center Hospital between 2002 and 2018 were retrospectively reviewed. @*Results@#Most cases were papillary carcinoma (n=26), with female predominance (n=25). Median age was 16.4 years (range, 11.9-18.6 years). Extrathyroidal extension was present in 24 cases. Twenty cases had tumor involvement at cervical lymph nodes and three had lung metastasis. Twenty-two patients received radioactive iodide treatment with a median cumulative dose of 300 mCi (range, 100-920 mCi). During a median follow-up of 68.2 months (range, 2.3-191.4 months), serum thyroglobulin level was elevated in 15 patients. Among them, two cases had remnant thyroid tissue, 4 had recurrence at cervical lymph nodes, and the remaining 9 did not have any detectable lesion. All were alive, and 5-year event-free survival (EFS) was 45.2±10.1%. Age £15 years, tumor size, lymph node status (N1b), and distant metastasis had negative effects on EFS. On multivariate analysis, age and tumor size had prognostic significance. @*Conclusion@#For DTC of children and adolescents (£18 years old), age ≤15 years and tumor size were prognostic factor. Therefore, patients in this age group need meticulous follow-up. Further studies are necessary to answer the potential influence of age on the incidence and behavior of DTC.

Clinical Usefulness of ¹⁸F-FC119S Positron-Emission Tomography as an Auxiliary Diagnostic Method for Dementia: An Open-Label, Single-Dose, Evaluator-Blind Clinical Trial

Measurement of Tumor Pressure and Strategies of Imaging Tumor Pressure for Radioimmunotherapy / 대한핵의학회잡지

Tumor interstitial pressure is a fundamental feature of cancer biology. Elevation in tumor pressure affects the efficacy of cancer treatment and results in the heterogenous intratumoral distribution of drugs and macromolecules. Monoclonal antibodies (mAb) play a prominent role in cancer therapy and molecular nuclear imaging. Therapy using mAb labeled with radionuclides—also known as radioimmunotherapy (RIT)—is an effective form of cancer treatment. RIT is clinically effective for the treatment of lymphoma and other blood cancers; however, its clinical use for solid tumor was limited because their high interstitial pressure prevents mAb from penetrating into the tumor. This pressure can be decreased using anti-cancer drugs or additional external therapy. In this paper, we reviewed the intratumoral pressure using direct tumor-pressure measurement strategies, such as the wick-in-needle and pressure catheter transducer method, and indirect tumor-pressure measurement strategies via magnetic resonance.

Measurement of Tumor Pressure and Strategies of Imaging Tumor Pressure for Radioimmunotherapy / 대한핵의학회잡지

Tumor interstitial pressure is a fundamental feature of cancer biology. Elevation in tumor pressure affects the efficacy of cancer treatment and results in the heterogenous intratumoral distribution of drugs and macromolecules. Monoclonal antibodies (mAb) play a prominent role in cancer therapy and molecular nuclear imaging. Therapy using mAb labeled with radionuclides—also known as radioimmunotherapy (RIT)—is an effective form of cancer treatment. RIT is clinically effective for the treatment of lymphoma and other blood cancers; however, its clinical use for solid tumor was limited because their high interstitial pressure prevents mAb from penetrating into the tumor. This pressure can be decreased using anti-cancer drugs or additional external therapy. In this paper, we reviewed the intratumoral pressure using direct tumor-pressure measurement strategies, such as the wick-in-needle and pressure catheter transducer method, and indirect tumor-pressure measurement strategies via magnetic resonance.

The Predictive Values of Lesion Size, F-18 FDG Avidity and I-131 Avidity for the Clinical Outcome of I-131 Treatment in Patients with Metastatic Differentiated Thyroid Carcinoma Only in the Lung / 대한핵의학회잡지

PURPOSE: We aimed to evaluate the prognostic values of radiography, F-18 FDG PET, and I-131 whole body scans in patients with lung-only metastasis from differentiated thyroid carcinoma (DTC).METHODS: Between 1998 and 2013, we included 31 patients (F: 26, M: 5) with lung-only metastasis from DTC who had been treated with I-131 and underwent PET. Lung metastasis was categorized according to the size (macronodular ≥1.0 cm vs. micronodular <1.0 cm), FDG avidity (avid vs. non-avid), and I-131 avidity (avid vs. non-avid). Progression-free survival (PFS) was evaluated for each patient.RESULTS: Among 31 patients, seven (23%) had macronodular lung metastasis, 26 (84%) had FDG avid lung metastasis, and 16 (52%) had I-131 avid lung metastasis. During the median follow-up period of 9.4 y, median PFS was 6.1 y. Based on Kaplan-Meier analysis, macronodular lung metastasis (p = 0.017) and I-131 non-avid lung metastasis (p = 0.059) were significantly associated with worse outcomes, but FDG avid lung metastasis was not (p = 0.135). Patients with FDG non-avid lung metastasis did not experience disease progression during follow-up, while 11 of 26 patients (42%) experienced disease progression. Based on univariate analysis, the hazard ratio for a poor prognosis was 3.78 (p = 0.029) for macronodular lung metastasis and 3.29 (p = 0.079) for I-131 non-avid lung metastasis.CONCLUSIONS: Macronodular and I-131 non-avid lung metastasis were associated with a poor prognosis in lung-only metastasis from DTC. Although FDG avid lung metastasis may be associated with a poor prognosis, a larger-scale study is needed.

The Predictive Values of Lesion Size, F-18 FDG Avidity and I-131 Avidity for the Clinical Outcome of I-131 Treatment in Patients with Metastatic Differentiated Thyroid Carcinoma Only in the Lung / 대한핵의학회잡지

PURPOSE@#We aimed to evaluate the prognostic values of radiography, F-18 FDG PET, and I-131 whole body scans in patients with lung-only metastasis from differentiated thyroid carcinoma (DTC).@*METHODS@#Between 1998 and 2013, we included 31 patients (F: 26, M: 5) with lung-only metastasis from DTC who had been treated with I-131 and underwent PET. Lung metastasis was categorized according to the size (macronodular ≥1.0 cm vs. micronodular <1.0 cm), FDG avidity (avid vs. non-avid), and I-131 avidity (avid vs. non-avid). Progression-free survival (PFS) was evaluated for each patient.@*RESULTS@#Among 31 patients, seven (23%) had macronodular lung metastasis, 26 (84%) had FDG avid lung metastasis, and 16 (52%) had I-131 avid lung metastasis. During the median follow-up period of 9.4 y, median PFS was 6.1 y. Based on Kaplan-Meier analysis, macronodular lung metastasis (p = 0.017) and I-131 non-avid lung metastasis (p = 0.059) were significantly associated with worse outcomes, but FDG avid lung metastasis was not (p = 0.135). Patients with FDG non-avid lung metastasis did not experience disease progression during follow-up, while 11 of 26 patients (42%) experienced disease progression. Based on univariate analysis, the hazard ratio for a poor prognosis was 3.78 (p = 0.029) for macronodular lung metastasis and 3.29 (p = 0.079) for I-131 non-avid lung metastasis.@*CONCLUSIONS@#Macronodular and I-131 non-avid lung metastasis were associated with a poor prognosis in lung-only metastasis from DTC. Although FDG avid lung metastasis may be associated with a poor prognosis, a larger-scale study is needed.

beta-irradiation (166Ho patch)-induced skin injury in mini-pigs: effects on NF-kappaB and COX-2 expression in the skin

In the present study, the detrimental effect of beta-emission on pig skin was evaluated. Skin injury was modeled in mini-pigs by exposing the animals to 50 and 100 Gy of beta-emission delivered by 166Ho patches. Clinicopathological and immunohistochemical changes in exposed skin were monitored for 18 weeks after beta-irradiation. Radiation induced desquamation at 2~4 weeks and gradual repair of this damage was evident 6 weeks after irradiation. Changes in basal cell density and skin depth corresponded to clinically relevant changes. Skin thickness began to decrease 1 week after irradiation, and the skin was thinnest 4 weeks after irradiation. Skin thickness increased transiently during recovery from irradiation-induced skin injury, which was evident 6~8 weeks after irradiation. Epidermal expression of nuclear factor-kappa B (NF-kappaB) differed significantly between the untreated and irradiated areas. One week after irradiation, cyclooxygenase-2 (COX-2) expression was mostly limited to the basal cell layer and scattered among these cells. High levels of COX-2 expression were detected throughout the full depth of the skin 4 weeks after irradiation. These findings suggest that NF-kappaB and COX-2 play roles in epidermal cell regeneration following beta-irradiation of mini-pig skin.

Quantitative Assessment Technology of Small Animal Myocardial Infarction PET Image Using Gaussian Mixture Model / 의학물리

Nuclear medicine images (SPECT, PET) were widely used tool for assessment of myocardial viability and perfusion. However it had difficult to define accurate myocardial infarct region. The purpose of this study was to investigate methodological approach for automatic measurement of rat myocardial infarct size using polar map with adaptive threshold. Rat myocardial infarction model was induced by ligation of the left circumflex artery. PET images were obtained after intravenous injection of 37 MBq 18F-FDG. After 60 min uptake, each animal was scanned for 20 min with ECG gating. PET data were reconstructed using ordered subset expectation maximization (OSEM) 2D. To automatically make the myocardial contour and generate polar map, we used QGS software (Cedars-Sinai Medical Center). The reference infarct size was defined by infarction area percentage of the total left myocardium using TTC staining. We used three threshold methods (predefined threshold, Otsu and Multi Gaussian mixture model; MGMM). Predefined threshold method was commonly used in other studies. We applied threshold value form 10% to 90% in step of 10%. Otsu algorithm calculated threshold with the maximum between class variance. MGMM method estimated the distribution of image intensity using multiple Gaussian mixture models (MGMM2, em leader MGMM5) and calculated adaptive threshold. The infarct size in polar map was calculated as the percentage of lower threshold area in polar map from the total polar map area. The measured infarct size using different threshold methods was evaluated by comparison with reference infarct size. The mean difference between with polar map defect size by predefined thresholds (20%, 30%, and 40%) and reference infarct size were 7.04+/-3.44%, 3.87+/-2.09% and 2.15+/-2.07%, respectively. Otsu verse reference infarct size was 3.56+/-4.16%. MGMM methods verse reference infarct size was 2.29+/-1.94%. The predefined threshold (30%) showed the smallest mean difference with reference infarct size. However, MGMM was more accurate than predefined threshold in under 10% reference infarct size case (MGMM: 0.006%, predefined threshold: 0.59%). In this study, we was to evaluate myocardial infarct size in polar map using multiple Gaussian mixture model. MGMM method was provide adaptive threshold in each subject and will be a useful for automatic measurement of infarct size.

Estimation of Internal Motion for Quantitative Improvement of Lung Tumor in Small Animal / 의학물리

The purpose of this study was to estimate internal motion using molecular sieve for quantitative improvement of lung tumor and to localize lung tumor in the small animal PET image by evaluated data. Internal motion has been demonstrated in small animal lung region by molecular sieve contained radioactive substance. Molecular sieve for internal lung motion target was contained approximately 37 kBq Cu-64. The small animal PET images were obtained from Siemens Inveon scanner using external trigger system (BioVet). SD-Rat PET images were obtained at 60 min post injection of FDG 37 MBq/0.2 mL via tail vein for 20 min. Each line of response in the list-mode data was converted to sinogram gated frames (2~16 bin) by trigger signal obtained from BioVet. The sinogram data was reconstructed using OSEM 2D with 4 iterations. PET images were evaluated with count, SNR, FWHM from ROI drawn in the target region for quantitative tumor analysis. The size of molecular sieve motion target was 1.59x2.50 mm. The reference motion target FWHM of vertical and horizontal was 2.91 mm and 1.43 mm, respectively. The vertical FWHM of static, 4 bin and 8 bin was 3.90 mm, 3.74 mm, and 3.16 mm, respectively. The horizontal FWHM of static, 4 bin and 8 bin was 2.21 mm, 2.06 mm, and 1.60 mm, respectively. Count of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.10, 4.83, 5.59, 5.38, and 5.31, respectively. The SNR of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.18, 4.05, 4.22, 3.89, and 3.58, respectively. The FWHM were improved in accordance with gate number increase. The count and SNR were not proportionately improve with gate number, but shown the highest value in specific bin number. We measured the optimal gate number what minimize the SNR loss and gain improved count when imaging lung tumor in small animal. The internal motion estimation provide localized tumor image and will be a useful method for organ motion prediction modeling without external motion monitoring system.

The Clinical Importance of Minimal Extrathyroid Extension on Tumor Recurrence in Patients with Papillary Thyroid Carcinoma

BACKGROUND: We wanted to evaluate whether a minimal extrathyroid extension (METE) is associated with the clinicopathological parameters that are indicative of a poor prognosis, including lymph node metastasis, distant metastasis at the time of the initial diagnosis and tumor recurrence, in patients with papillary thyroid carcinoma (PTC), and especially in the patients with papillary thyroid microcarcinoma (PTMC). METHODS: We retrospectively evaluated the medical records of patients with PTC and who had undergone total thyroidectomy with/without subsequent 131I remnant ablation at the Korea Cancer Center Hospital from January 1998 through December 2005. A total of 557 patients with PTC were enrolled in the study. We excluded 13 patients with an unknown status of extension and 29 patients with massive ETE. RESULTS: Of the 515 patients, 401 were found to have a METE. We analyzed the 464 patients who were without distant metastasis at the time of the initial diagnosis and who had a follow-up duration of more than 6 months. METE was not significantly associated with tumor recurrence during the follow-up period (median follow-up period: 122 months, range: 6-142 months): 8% vs. 15% of the patients with and without METE had tumor recurrence, respectively (P = 0.069 by the log-rank test). We analyzed the effect of tumor size in the patients with METE. Size was not significantly associated with tumor recurrence (P = 0.374 by the log-rank test). CONCLUSION: These findings suggest that METE might not be a prognostic factor to predict tumor recurrence in patients with PTC, including PTMC.

Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression with Radiolabeled 5-(2-iodovinyl)-2'-deoxyuridine (IVDU) in Liver by Hydrodynamic-based Procedure / 핵의학분자영상

PURPOSE: Hydrodynamic-based procedure is a simple and effective gene delivery method to lead a high gene expression in liver tissue. Non-invasive imaging reporter gene system has been used widely with herpes simplex virus type 1 thymidine kinase (HSV1-tk) and its various substrates. In the present study, we investigated to image the expression of HSV1-tk gene with 5-(2-iodovinyl)-2'-deoxyuridine (IVDU) in mouse liver by the hydrodynamicbased procedure. MATERIALS AND METHODS: HSV1-tk or enhanced green fluorescence protein (EGFP) encoded plasmid DNA was transferred into the mouse liver by hydrodynaminc injection. At 24 h post-injection, RT-PCR, biodistribution, fluorescence imaging, nuclear imaging and digital wholebody autoradiography (DWBA) were performed to confirm transferred gene expression. RESULTS: In RT-PCR assay using mRNA from the mouse liver, specific bands of HSV1-tk and EGFP gene were observed in HSV1-tk and EGFP expressing plasmid injected mouse, respectively. Higher uptake of radiolabeled IVDU was exhibited in liver of HSV1-tk gene transferred mouse by biodistribution study. In fluorescence imaging, the liver showed specific fluorescence signal in EGFP gene transferred mouse. Gamma-camera image and DWBA results showed that radiolabeled IVDU was accumulated in the liver of HSV1-tk gene transferred mouse. CONCLUSION: In this study, hydrodynamic-based procedure was effective in liver-specific gene delivery and it could be quantified with molecular imaging methods. Therefore, co-expression of HSV1-tk reporter gene and target gene by hydrodynamic-based procedure is expected to be a useful method for the evaluation of the target gene expression level with radiolabeled IVDU.

Production and Evaluation of Immunoreactivity of Poly Lysine-Tagged Single Chain Fragment Variable (ScFv) Lym-1 Antibody for Direct Conjugation to Fluorescence Dye / 핵의학분자영상

PURPOSE: Small size of recombinant scFv antibody has many advantages such as rapid blood clearances and improved targeting antibodies to tumor region. On the other hand owing to small size, number of amino group is insufficient in conjugation with chelator and fluorescence labeling. This study is to introduce poly lysine tag to the C-terminal end of scFv lym-1 sequence for fluorescence chelator conjugation. MATERIALS AND METHODS: Poly lysine scFv lym-1 gene, cloned into pET-22b (+) vector, was expressed in E. coli BL21 (DE3) strain. Antibody purification was performed with Ni-NTA column and then size exclusion column chromatography. Expression and purification levels of poly lysine tagged scFv lym-1 antibody were confirmed by western blot analysis. I-124, I-125, I-131 and Tc-99m were used for radiolabeling of purified poly lysine scFv lym-1. Flow cytometry analysis of FITC conjugated poly lysine scFv lym-1 was performed for confirmation of immunoreactivity of human Burkitt`s lymphoma cells. RESULTS: Poly lysine scFv lym-1 antibody was purified through two steps and identified as molecular weight of 48 KDa. Radiolabeling yields of I-124, I-125, I-131 and Tc-99m into poly lysine scFv lym-1 were >99%, >99%, >95% and >99%, respectively. Flow cytometry analysis of poly lysine scFv and scFv lym-1 was showed similar immunoreactivity to human Burkitt`s lymphoma cells. CONCLUSION: Poly lysine tag was useful for the sufficient number of amino groups to scFv lym-1 antibody for chelator conjugation with minimizing loss of immunoreactivity.

mage-Based Assessment and Clinical Significance of Absorbed Radiation Dose to Tumor in Repeated High-Dose (131)I Anti-CD20 Monoclonal Antibody (Rituximab) Radioimmunotherapy for Non-Hodgkin's Lymphoma / 핵의학분자영상

PURPOSE: We assessed the absorbed dose to the tumor (Dosetumor) by using pretreatment FDG-PET and whole-body (WB) planar images in repeated radioimmunotherapy (RIT) with 131I rituximab for NHL. MATERIALS AND METHODS: Patients with NHL (n=4) were administered a therapeutic dose of (131)I rituximab. Serial WB planar images after RIT were acquired and overlaid to the coronal maximum intensity projection (MIP) PET image before RIT. On registered MIP PET and WB planar images, 2D-ROIs were drawn on the region of tumor (n=7) and left medial thigh as background, and Dosetumor was calculated. The correlation between Dosetumor and the CT-based tumor volume change after RIT was analyzed. The differences of Dosetumor and the tumor volume change according to the number of RIT were also assessed. RESULTS: The values of absorbed dose were 397.7+/-646.2cGy (53.0~2853.0cGy). The values of CT-based tumor volume were 11.3+/-9.1 cc (2.9~34.2cc), and the % changes of tumor volume before and after RIT were -29.8+/-44.3% (-100.0%~+42.5%), respectively. Dosetumor and the tumor volume change did not show the linear relationship (p>0.05). Dosetumor and the tumor volume change did not correlate with the number of repeated administration (p>0.05). CONCLUSION: We could determine the position and contour of viable tumor by MIP PET image. And, registration of PET and gamma camera images was possible to estimate the quantitative values of absorbed dose to tumor.

Bone Mineral Density Measurement of Rats Using Dual-energy X-ray Absorptiometry: Precision of In Vivo Measurements for Various Skeletal Sites with or without Repositioning / 핵의학분자영상

PURPOSE: Bone mineral density (BMD) measurements need to be precise enough to be capable of detecting small changes in bone mass of rats. Using a regular dual-energy X-ray absorptiometry (DXA), we measured many BMD of various skeletal sites in rats to examine precision of DXA in relation to the repositioning on the bones of rats. MATERIALS AND METHODS: Using DXA and small animal software, scans were performed 4 times in all 12 male rats without repositioning (Group 1a). Another four scans for 6 of 12 rats were done with repositioning between scans (Group 2). Customized regions of interest (ROIs), encapsulate the right hind limb, L1-4, skull and pelvic bones were drawn at each measurement. The precision of the measurements was evaluated by measuring the coefficient of variation (CV) of four measurements of BMD at each skeletal site of all rats with or without repositioning. Significance of differences between group 1b (six rats out of group 1a, which were come under group 2) and group2 were evaluated with Wilcoxon Signed Rank Sum Test. RESULTS: CVs obtained at different skeletal sites of all measurements in Group 1b and 2. It was 3.51+/-1.20, 2.62+/-1.20 for the hindlimb (p=0.173), 3.83+/-2.02, 4.59+/-2.02 for L1-4 (p=0.600), 3.73+/-1.87, 1.53+/-0.89 for skull (p=0.046), and 2.92+/-0.60, 1.45+/-0.60 for pelvic bones (p=0.075). CONCLUSION: Our study demonstrates that the DXA technique has the precision necessary when used to assess BMD for various skeletal sites in rats regardless of repositioning.

Medical Application of Radiation Internal Dosimetry / 핵의학분자영상

Medical internal radiation dosimetry (MIRD) is an important part of nuclear medicine research field using therapeutic radioisotope. There have been many researches using MIRD for the development of new therapeutic approaches including radiopharmaceutical, clinical protocol, and imaging techniques. Recently, radionuclide therapy has been re-focused as new solution of intractable diseases, through to the advances of previous achievements. In this article, the basic concepts of radiation and internal radiation dosimetry are summarized to help understanding MIRD and its application to clinical application.

Small Animal PET Imaging with 124IFIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model / 핵의학분자영상

PURPOSE: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the develoopement of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-beta-D-arabino-furanosyl-5-[124/125I]iodo- uracil ([124/125I]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. MATERIAL AND METHODS: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [125I]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [124I]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. RESULTS: Specific accumulation of [125I]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [125I]FIAU uptake was linearly correlated (R2=0.964, p=0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [125I]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small aninal PET, [124I]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. CONCLUSION: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.

Imaging of Lung Metastasis Tumor Mouse Model using 18FFDG Small Animal PET and CT / 핵의학분자영상

PURPOSE: The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using [18F]FDG small animal PET and clinical CT. MATERIALS AND METHODS: The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at 30 degrees C. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq [18F]FDG and compared pattern of [18F]FDG uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, [18F]FDG image was obtained and fused with anatomical clinical CT image. RESULTS: Average blood glucose concentration in normal mice were 128.0+/-23.87 and 86.0+/-21.65 mg/dL in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was 8.6+/-0.48 and 12.1+/-0.63 in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, [18F]FDG image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in [18F]FDG small animal PET image was confirmed by fusion image using clinical CT. CONCLUSION: Tumor imaging in small animal lung region with [18F]FDG small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during [18F]FDG uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.

Internal Radiation Dosimetry using Nuclear Medicine Imaging in Radionuclide Therapy / 핵의학분자영상

Radionuclide therapy has been an important field in nuclear medicine. In radionuclide therapy, relevant evaluation of internally absorbed dose is essential for the achievement of efficient and sufficient treatment of incurable disease, and can be accomplish by means of accurate measurement of radioactivity in body and its changes with time. Recently, the advances of nuclear medicine imaging and multi?modality imaging processing techniques can provide chance of more accurate and easier measurement of the measures commented above, in cooperation of conventional imaging?based approaches. In this review, basic concept for internal dosimetry using nuclear medicine imaging is summarized with several check points which should be considered in real practice.