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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.
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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.
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BACKGROUND@#AND PURPOSE: The aim of this study was to determine the diagnostic performance and safety of a new ¹â¸F-labeled amyloid tracer, ¹â¸F-FC119S.@*METHODS@#This study prospectively recruited 105 participants, comprising 53 with Alzheimer's disease (AD) patients, 16 patients with dementia other than AD (non-AD), and 36 healthy controls (HCs). In the first screening visit, the Seoul Neuropsychological Screening Battery cognitive function test was given to the dementia group, while HC subjects completed the Korean version of the Mini Mental State Examination. Individuals underwent ¹â¸F-FC119S PET, ¹â¸F-fluorodeoxyglucose (FDG) PET, and brain MRI. The diagnostic performance of ¹â¸F-FC119S PET for AD was compared to a historical control (comprising previously reported and currently used amyloid-beta PET agents), ¹â¸F-FDG PET, and MRI. The standardized uptake value (SUV) ratio (ratio of the cerebral cortical SUV to the cerebellar SUV) was measured for each PET data set to provide semiquantitative analysis. All adverse effects during the clinical trial periods were monitored.@*RESULTS@#Visual assessments of the ¹â¸F-FC119S PET data revealed a sensitivity of 92% and a specificity of 84% in detecting AD. ¹â¸F-FC119S PET demonstrated equivalent or better diagnostic performance for AD detection than the historical control, ¹â¸F-FDG PET (sensitivity of 80.0% and specificity of 76.0%), and MRI (sensitivity of 98.0% and specificity of 50.0%). The SUV ratios differed significantly between AD patients and the other groups, at 1.44±0.17 (mean±SD) for AD, 1.24±0.09 for non-AD, and 1.21±0.08 for HC. No clinically significant adverse effects occurred during the trial periods.@*CONCLUSIONS@#¹â¸F-FC119S PET provides high sensitivity and specificity in detecting AD and therefore may be considered a useful diagnostic tool for AD.
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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.
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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.
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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.
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Anticorps monoclonaux , Biologie , Cathéters , Lymphomes , Méthodes , Radioimmunothérapie , TransducteursRésumé
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.
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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.
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Humains , Évolution de la maladie , Survie sans rechute , Études de suivi , Estimation de Kaplan-Meier , Poumon , Métastase tumorale , Pronostic , Radiographie , Glande thyroide , Tumeurs de la thyroïde , Imagerie du corps entierRésumé
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.
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Animaux , Mâle , Cyclooxygenase 2/génétique , Holmium , Facteur de transcription NF-kappa B/génétique , Lésions radiques expérimentales/métabolisme , Peau/métabolisme , Suidae , Porc miniatureRésumé
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.
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Animaux , Poumon , VeinesRésumé
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.
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Animaux , Rats , Artères , Électrocardiographie , Fluorodésoxyglucose F18 , Infarctus , Injections veineuses , Ligature , Infarctus du myocarde , Myocarde , Médecine nucléaire , Oligosaccharides , PerfusionRésumé
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.
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Humains , Carcinomes , Carcinome papillaire , Facteur IX , Études de suivi , Corée , Noeuds lymphatiques , Dossiers médicaux , Métastase tumorale , Pronostic , Récidive , Études rétrospectives , Glande thyroide , Tumeurs de la thyroïde , ThyroïdectomieRésumé
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.
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Animaux , Humains , Mâle , Rats , Absorptiométrie photonique , Densité osseuse , Membres , Membre pelvien , Os coxal , CrâneRésumé
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.
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Humains , Anticorps monoclonaux d'origine murine , Caméras à rayons gamma , Lymphomes , Lymphome malin non hodgkinien , Radioimmunothérapie , Cuisse , Charge tumorale , RituximabRésumé
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.
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Humains , Anticorps , Technique de Western , Chromatographie , Clones cellulaires , Cytométrie en flux , Fluorescéine-5-isothiocyanate , Fluorescence , Main , Lymphomes , Lysine , Masse moléculaire , Entorses et fouluresRésumé
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.
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Animaux , Souris , Autoradiographie , ADN , Fluorescence , Expression des gènes , Gènes rapporteurs , Herpès , Herpèsvirus humain de type 1 , Idoxuridine , Foie , Méthacrylates de méthyle , Imagerie moléculaire , Imagerie optique , Plasmides , Polystyrènes , ARN messager , Simplexvirus , Thymidine kinaseRésumé
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.
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Animaux , Humains , Souris , Arabinofuranosyluracile , Carcinome hépatocellulaire , Numération cellulaire , Lignée cellulaire , Gènes rapporteurs , Thérapie génétique , Herpès , Herpèsvirus humain de type 1 , Foie , Tumeurs expérimentales du foie , Méthacrylates de méthyle , Polystyrènes , Simplexvirus , Statistiques comme sujet , Uracile , UrsidaeRésumé
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.
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Accomplissement , Protocoles cliniques , Médecine nucléaire , RadiométrieRésumé
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.
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Médecine nucléaire , Radioactivité , RadiométrieRésumé
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.