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.

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

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.

Intracavitary Radiation Therapy for Recurrent Cystic Brain Tumors with Holmium-166-Chico : A Pilot Study

OBJECTIVE: Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. METHODS: Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. RESULTS: There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. CONCLUSION: Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

A Case of Transient Memory Impairment after Acute Left Focal Lateral Putamen ICH with Old Caudate Nucleus Infarction

Transient memory impairment can be occurred by many causes. One of them is acute focal brain lesion in strategic site. Caudate nucleus and medial basal ganglia (globus pallidus) are lesion of strategic site. They play its role in cognitive processing. But lateral basal ganglia (putamen) is known as a structure involving movement, not cognitive function. We report a interesting case of transient memory dysfunction with acute focal putamen ICH with old caudate nucleus infarction.

Charles Bonnet Syndrome Following Bilateral Occipital Infarction

No abstract available.

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.

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.

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.

Production of the Recombinant Single Chain Anti-B Cell Lymphoma Antibody and Evaluation of Immunoreactivity / 핵의학분자영상

PURPOSE: Recombinant ScFv lym-1 was produced, using pET vector system for large scale production. METHODS: ScFv lym-1 gene inserted pET-22b (+) vector, was expressed in E.coli BL-21 strain. ScFv lym-1 antibody extracted from periplasm, was purified with His-Taq column. To evaluated immunoreactivity with Raji cell, ScFv lym-1 was labeled with I-125 and I-125 ScFv lym-1 was purified with desalting column. Raji cell was injected into the C57BR/cdJ SCID mice. Gamma camera imaging were taken time point at 1, 8, 24, and 48 hr with 8 mm pinhole collimator. RESULTS: An active scFv lym-1 could be produced in E.coli with soluble from using pET vector system. Immunoreactivity and affinity constant of IgG lym-1 were 54% and 1.83 x 10(9) M(-1), respectively, and those of scFv lym-1 were 53.7% and 1.46 x 10(9) M(-1), respectively. Biodistribution of I-125 scFv lym-1 antibody showed faster clearance in blood, spleen, kidney and than I-125 IgG lym-1 antibody. Gamma camera image of I-125 scFv lym-1 antibody showed faster clearance and tumor targeting liver than I-125 IgG lym-1 antibody. CONCLUSIONS: In vitro properties of scFv lym-1 were similar to those of IgG lym-1. ScFv lym-1 showed faster blood clearance than IgG lym-1. These results suggest that scFv lym-1 antibody can be useful for tumor imaging agent.

Synthesis and Preliminary Evaluation of 9-(4-18FFluoro-3-hydroxymethylbutyl) Guanine (18FFHBG) in HSV1-tk Gene Transduced Hepatoma Cell / 핵의학분자영상

PURPOSE: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. MATERIALS AND METHODS: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with K[18F]/K2.2.2. in acetonitrile using N2-monomethoxytrityl-9-[4-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of [18F]FHBG were performed, and was analyzed correlation between [18F]FHBG uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. RESULTS: [18F]FHBG was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiochemical yield was about 20-25% (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 GBq/micro mol. Specific accumulation of [18F]FHBG was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked [18F]FHBG was retained inside of cells. The uptake of [18F]FHBG was showed a highly significant linear correlation (R2=0.995) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. CONCLUSION: [18F]FHBG appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

The Role of F-18 Fluorodeoxyglucose Positron Emission Tomography in Patients with Malignant Mixed Mullerian Tumors of the Uterus / 핵의학분자영상

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 histopathological 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+/-12.2 months). The mean disease free intervals of these 7 patients were 36.4+/-6.0 months. Two patients with abnormal findings had never become disease-free condition during the follow up period (6.0+/-4.2 months. CONCLUSION: FDG PET could be a useful modality for unexpected distant metastasis and follow up tool in patients with MMMT.

Utiliy of Breast Sentinel Lymph Node Biopsy Using the Day-Before or the Same-Day Subareolar Injection of (99m)Tc-Tin Colloid / 한국유방암학회지

PURPOSE: The aims of this study were to examine the feasibility of sentinel lymph node (SLN) biopsy using the day-before-surgery or the same-day subareolar injection of (99m)Tc-Tin colloid, and to evaluate the accuracy of performing intraoperative multiple frozen section diagnosis of the SLN for breast cancer. METHODS: From Jul. 2003 to Feb. 2004, a total of 81 women with clinically node negative breast cancer underwent SLN biopsy and this was followed by axillary lymph node dissection at the Korea Cancer Center Hospital. 2-2.5mCi of (99m)Tc-Tin colloid was injected intradermally in the outer upper edge of the areola on the day before or the same day of surgery, and lymphoscintigraphy was then obtained. The time interval between the injection of tracer and SLN biopsy varied from 1 hour to 20 hours. Intraoperatively, the status of the SLNs was examined by multiple frozen section diagnosis and all the SLNs were subjected to serial sectioning for Hematoxylin-eosin staining and immunohistochemical staining for cytokeratin. After removal of the SLNs, standard level I and II axillary dissection was performed in all patients. RESULTS: In 26 patients (32.1%), the SLNs were positive for tumor cells among these 26 patients. 16 patients (61.5%) results showed that the SLNs were the only metastatic nodes. Two cases of false negative findings were identified. The sensitivity and specificity were 92.9% and 100% respectively. In the second half of this study, no false-negative cases were found in 41 consecutive patients. CONCLUSION: The results of SLN biopsy using the day-before-surgery or same-day subareolar injection of (99m)Tc-Tin colloid were excellent for identification of the SLNs. This technique does not interfere with effective treatment in the operating room because the time interval between the injection and surgery did not affect the results of SLN biopsy. Intraoperative multiple frozen section diagnosis of SLNs was readily available, and this was highly accurate for assessing the status of SLNs

A Study on Preparation of 3'-18FFluoro-3'-deoxythymidine and Its Biodistribution in 9L Glioma Bearing Rats / 핵의학분자영상

PURPOSE: Several radioisotope-labeled thymidine derivatives such as [11C]thymidine was developed to demonstrate cell proliferation in tumor. But it is difficult to track metabolism with [11C]thymidine due to rapid in vivo degradation and its short physical half-life. 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) was reported to have the longer half life of fluorine-18 and the lack of metabolic degradation in vivo. Here, we described the synthesis of the 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) and compared with [18F]FET and [18F]FDG in cultured 9L cell and obtained the biodistribution and PET image in 9L tumor bearing rats. MATERIAL AND METHOD: For the synthesis of [18F]FLT, 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-beta-D-threopentofuranosyl)thymine was used as a FLT precursor, on which the tert-butyloxycarbonyl group was introduced to protect N3-position and nitrobenzenesulfonyl group. Radiolabeling of nosyl substitued precursor with 18F was performed in acetonitrile at 120 degrees C and deproteced with 0.5 N HCl. The cell uptake was measured in cultured 9L glioma cell. The biodistribution was evaluated in 9L tumor bearing rats after intravenous injection at 10 min, 30 min, 60 min and 120 min and obtained PET image 60 minutes after injection. RESULTS: The radiochemical yield was about 20-30% and radiochemical purity was more than 95% after HPLC purification. Cellular uptake of [18F]FLT was increased as time elapsed. At 120 min post-injection, the ratios of tumor/blood, tumor/muscle and tumor/brain were 1.61+/-0.34, 1.70+/-0.30 and 9.33+/-2.22, respectively. The 9L tumor was well visualized at 60 min post injection in PET image. CONCLUSION: The uptake of [18F]FLT in tumor was higher than in normal brain and PET image of [18F]FLT was acceptable. These results suggest the possibility of [18F]FLT as an imaging agent for brain tumor.