Biomedical subjects

June-Key Chung

Publications and source records attributed to June-Key Chung.

At least 19 recordsLinked to original sources

PubMed2007

Characterization of surgically transposed ovaries in integrated PET/CT scan in patients with cervical cancer.

BACKGROUND: The purpose of this study was to determine the ovarian findings on integrated positron emission tomography/computed tomography scans during follow-up in cervical cancer patients with ovarian transposition. METHOD: We retrospectively reviewed the clinical data and integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography of women with ovarian transposition during radical hysterectomy for cervical cancer between December 2003 and March 2006. RESULTS: Eighty-four premenopausal women had ovarian transposition performed during the study period. Twelve positron emission tomography/computed tomography scans from 11 patients were registered for the current study and three women were diagnosed with metastasis: two in lung and one in pelvis. Two patients complained of menopausal symptoms during follow-up, and the hormonal tests were consistent with it. In the current study, an integrated positron emission tomography/computed tomography scan detected one patient with right lower abdominal mass with increased 18F-fluorodeoxyglucose uptake, which was identified as a transposed right ovary. Clinical information of ovarian transposition was helpful in interpretation of the lesion. In the patient, transposed ovary was associated with increased fluorodeoxyglucose uptake, with standard uptake values ranging from 3.7 to 5.5. Other positron emission tomography/computed tomography scans did not show abnormal uptake of 18F-fluorodeoxyglucose. CONCLUSIONS: Transposed ovary in premenopausal women may appear on integrated positron emission tomography/computed tomography scan as a mass with increased 18F-fluorodeoxyglucose uptake, which may be associated with preserved ovarian function. Clinical information regarding transposition should be noted in order not to interpret these as recurrent or metastatic lesions.

Adult↗

PubMed2006

Consideration of serum glucose levels during malignant mediastinal lymph node detection in non-small-cell lung cancer by FDG-PET.

BACKGROUND AND OBJECTIVE: Glucose and FDG compete for uptake by cancers. Here, we undertook to improve diagnostic accuracy of FDG-PET for determining mediastinal lymph node (LN) status in NSCLC by considering serum glucose level. METHODS: NSCLC patients (n = 70) who underwent curative lung resection and mediastinal LN dissection within 1 month of FDG-PET were enrolled. MaxSUV was calculated using lean body weight and used to determine a new parameter (maxSUV x serum glucose level; maxSUV-GL). Histopathologic LN results were compared with maxSUV and maxSUV-GL values. RESULTS: Of 71 LN stations whose FDG uptake could be measured, 21 were malignant and 50 benign. MaxSUV of LN had AUC of 0.729 (95% CI: 0.610-0.827) by ROC analysis with sensitivity of 47.6% (10/21), specificity of 94.0% (47/50), and a cutoff value of 3.3. Using maxSUV-GL the corresponding values were; AUC 0.825 (95% CI: 0.716-0.905) and sensitivity 76.2% (16/21), with a cutoff value of 290.4, which represented a significant improvement (P < 0.01) without compromising specificity 88.0% (44/50) (P > 0.05). The exclusion of neo-adjuvant chemotherapeutic and diabetic patients resulted in a similar improvement in diagnostic accuracy. CONCLUSION: By considering serum glucose level during FDG-PET using the new parameter maxSUV-GL, sensitivity for malignant mediastinal LN detection is improved.

Blood Glucose↗

PubMed2006

Establishment and characterization of cell lines from three human thyroid carcinomas: responses to all-trans-retinoic acid and mutations in the BRAF gene.

We report the characteristics of three cell lines (designated, SNU-80, SNU-373 and SNU-790), which were established from two papillary carcinomas and one anaplastic carcinoma obtained from three Korean thyroid carcinoma patients. All cell lines grow as adherent cells. Electron microscopy characteristically showed cytoplasmic invaginations of nuclei and intranuclear cytoplasmic inclusions. SNU-80 and SNU-790 cells showed a positive reaction to anti-cytokeratin antibody, and SNU-790 cells positivity for CK-19. All lines were free of mycoplasma or bacteria and were proven unique by DNA fingerprinting analysis. The p15 and p16 genes are deleted in the SNU-790 line. Mutations of the p53 gene were found in two lines (SNU-80 and SNU-373), but no mutations in the RET or MEN1 genes were observed. Mutations of the BRAF gene were found in the SNU-80 (G468R) and the SNU-790 (V599E) cell lines, but no mutations in the K-ras gene were present. SNU-80 and SNU-790 cells showed a positive reaction to anti-cytokeratin antibody, and no evidence of the production of thyroglobulin or calcitonin was observed. The cell lines were unable to trap radioactive iodine but did not contain TSH receptor. In addition, we investigated the mRNA expression levels of Tg, TSHR, TTF-1, PAX-8, NIS, IL-6, and LIF, and of the alpha, beta and gamma retinoic acid receptors in these cell lines. IL-6 was down-regulated in all three cell lines by all-trans-retinoic acid treatment. RAR-alpha was expressed but RAR-beta was not expressed in the three cell lines, and RAR-gamma was not expressed in SNU-790. Interestingly, RAR-beta (SNU-80 and SNU-373) and RAR-gamma (SNU-790) was up-regulated by all-trans-retinoic acid treatment. We believe that these well-characterized thyroid carcinoma cell lines may be useful tools for investigations on the biological characteristics of thyroid carcinoma, particularly for investigations related to gene alterations, especially of the BRAF gene. These cell lines may also be useful for redifferentiation therapy studies on thyroid carcinoma using all-trans-retinoic acid.

Antineoplastic Agents↗

PubMed2006

Role of [18F]FDG PET/CT in the assessment of suspected recurrent ovarian cancer: correlation with clinical or histological findings.

PURPOSE: To evaluate the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) for depiction of suspected recurrent ovarian carcinoma after treatment, with use of clinical or histological findings as the reference standard. METHODS: Seventy-seven women (median age, 51 years) with ovarian carcinoma treated with primary cytoreductive surgery followed by platinum-based combination chemotherapy were included, and [18F]fluorodeoxyglucose (FDG) PET/CT was performed for suspected recurrence. In all patients, imaging findings were compared with results of histological examination after surgical exploration or clinical follow-up to determine the diagnostic accuracy of PET/CT in the evaluation of disease status. Fisher's exact test was used to measure the ability of PET/CT to predict recurrent lesions. RESULTS: Forty-five (58.4%) of the 77 patients had documented recurrence during surgical exploration or clinical follow-up, while 32 (41.6%) had no evidence of recurrent tumour. Of the 45 patients with recurrent disease, 27 (60%) were confirmed to have recurrence by surgical biopsy. A correlation was found between PET/CT and histological or clinical analyses (kappa = 0.894). The overall sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT were 93.3%, 96.9%, 94.8%, 97.7% and 91.2%, respectively. PET/CT modified the diagnostic or treatment plan in 19 (24.7%) patients, by leading to the use of previously unplanned therapeutic procedures in 11 (57.9%) patients and the avoidance of previously planned diagnostic procedures in eight (42.1%) patients. CONCLUSION: Integrated FDG PET/CT is a sensitive post-therapy surveillance modality for the detection of recurrent ovarian cancer; it aids decisions on treatment plans and may ultimately have a favourable impact on prognosis.

Adult↗

PubMed2006

Lymph node metastasis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging versus PET/CT in a rabbit model.

PURPOSE: To prospectively compare the diagnostic accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging and integrated positron emission tomography-computed tomography (PET/CT) for the depiction of lymph node metastasis in an animal model, with histologic findings as the reference standard. MATERIALS AND METHODS: This experiment was approved by the local animal care committee. VX2 carcinoma was implanted into the thighs of 11 rabbits 4 weeks before the imaging study. T2- and T2*-weighted MR examinations were performed 24 hours after USPIO administration, followed by integrated PET/CT. USPIO-enhanced MR imaging and PET/CT analysis for the evaluation of the presence of metastasis in iliac lymph nodes were performed independently by two radiologists and two nuclear medicine physicians, respectively, without histopathologic knowledge. Results were evaluated by using receiver operating characteristic (ROC) analysis, and sensitivities and specificities were compared by using a Z test. RESULTS: Metastases were histopathologically confirmed in 22 of 62 iliac lymph nodes. USPIO-enhanced MR imaging showed a significantly greater area under the ROC curve than did PET/CT (0.984 vs 0.852; P=.023). The respective sensitivity and specificity for the detection of lymph node metastasis were 91% (20 of 22) and 95% (38 of 40) for USPIO-enhanced MR imaging and 64% (14 of 22) and 98% (39 of 40) for PET/CT. In terms of sensitivity, a significant difference was found between USPIO-enhanced MR imaging and PET/CT, particularly for nodal metastasis of less than 5 mm (86% [six of seven] vs 0% [zero of seven]; P=.031), whereas the specificity of the two imaging modalities was similar (P=.226). CONCLUSION: USPIO-enhanced MR imaging results in higher diagnostic accuracy for depicting lymph node metastasis than does PET/CT.

Animals↗

PubMed2006

Clinical impact of integrated PET/CT on the management of suspected cervical cancer recurrence.

OBJECTIVES: To assess the value and clinical impact of integrated PET/CT using (18)F-FDG in the diagnosis and management of women with suspected cervical cancer recurrence. METHODS: Fifty-two patients with cervical cancer with suspected recurrence because of clinical, cytological, biochemical and radiological findings were retrospectively evaluated. A final diagnosis of recurrence was confirmed by histologic tissue biopsy or by further clinical or radiological evidence. The clinical impact of information provided by PET/CT on patient management was assessed on the basis of clinical follow-up data concerning further diagnostic or therapeutic approach. RESULTS: Twenty-eight of 32 positive PET/CT scans (87.5%) were proven to have recurrent disease. Seventeen of 20 negative PET/CT scans (85.0%) had no evidence of disease. The sensitivity, specificity, and accuracy of PET/CT for detecting recurrence were 90.3%, 81.0%, and 86.5% respectively. PET/CT changed the management of 12 patients (23.1%) by changing treatment plan (5 patients), by initiating unplanned treatment strategy (4 patients), or by obviating the need for planned diagnostic procedures (3 patients). Median duration after performing PET/CT and last follow-up was 12 (range: 6-27) months, and the 2-year disease-free survival rate of patients with negative PET/CT scan for recurrence was significantly better than that of patients with positive PET/CT (85.0% vs. 10.9%, P=0002). CONCLUSIONS: In patients with a suspected recurrence of cervical cancer, integrated PET/CT using (18)F-FDG provides good anatomic and functional localization of suspicious lesions, and the better diagnostic interpretation has an impact not only on clinical management and treatment planning of patients, but also on disease-free survival.

Adult↗

PubMed2006

Development of acetylated HDD kit for preparation of 188Re-HDD/lipiodol.

A lipiodol solution of (188)Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol ((188)Re-HDD/lipiodol) is in clinical study for liver cancer therapy. However, formulation of it is difficult due to highly active and unstable sulfhydryl groups. We produced new kits using diacetylated HDD (AHDD), in which sulfhydryl groups are protected. We found that AHDD kit can replace HDD kit due to an increased stability for formulation, the better radiolabeling efficiency (78%) and the equivalent biodistribution pattern in mice.

Acetylation↗

PubMed2006

High fluorodeoxyglucose uptake on positron emission tomography in patients with advanced non-small cell lung cancer on platinum-based combination chemotherapy.

PURPOSE: To evaluate response and survival for platinum-based combination chemotherapy in chemonaive patients with non-small cell lung cancer (NSCLC) according to pretreatment standardized uptake values (SUV) by fluorodeoxyglucose positron emission tomography. EXPERIMENTAL DESIGN: Patients with advanced NSCLC who had not previously received chemotherapy were eligible. Response rates and survivals were analyzed according to maximal SUVs [low ( 7.5), where 7.5 was the median value] before the first cycle of chemotherapy. RESULTS: Eighty-five consecutive patients were included in the retrospective study. Patients with high SUV tumors exhibited significantly higher response rates (34.1% for low SUVs versus 61.0% for high SUVs; P = 0.013). Other factors, including sex, age, histology, performance status, number of involved organs, regimens used, and disease stage, did not affect response. However, high SUVs were related with a shorter response duration (279 days for low SUVs versus 141 days for high SUVs; P = 0.003) and time to progression (282 days for low SUVs versus 169 days for high SUVs; P = 0.015). Overall survival was unaffected by maximal SUVs (623 days for low SUVs versus 464 days for high SUVs; P = 0.431). CONCLUSIONS: Patients having NSCLC with high maximal SUVs showed a better response to platinum-based combination chemotherapy but had a shorter time to progression. Tumor glucose metabolism, as determined by SUVs on fluorodeoxyglucose positron emission tomography, was found to discriminate NSCLC subsets with different clinical and biological features.

Aged↗

PubMed2006

An improved method of 18F peptide labeling: hydrazone formation with HYNIC-conjugated c(RGDyK).

Radiolabeled alpha(v)beta(3)-integrin antagonists are increasingly investigated as a means of imaging angiogenesis. Several methods of labeling alpha(v)beta(3)-integrin binding peptide with (18)F have been reported recently. In the present study, we devised a straightforward means for labeling Arg-Gly-Asp (RGD) peptide with (18)F via hydrazone formation between c(RGDyK)-hydrazinonicotinic acid (HYNIC) (3) and 4-[(18)F]-fluorobenzaldehyde ([(18)F]4). The resulting reaction mixture was purified by HPLC to give 4'-[(18)F]-fluorobenzylidenehydrazone-6-nicotinamide-c(RGDyK) ([(18)F]5). The conjugation efficiency of 3 and 4 to form [(18)F]5 was 95.2%, and the radiochemical purity of [(18)F]5 after purification was >99%. The specific activity of [(18)F]5 estimated by radio-HPLC was 20.5 GBq/mumol (end of synthesis). Competitive binding assay of c(RGDyK) (1) and 5 was performed using [(125)I]iodo-c(RGDyK) as a radioligand, and K(i) values were found to be 2.8 and 21.7 nM, respectively. For the biodistribution study, the angiogenic mouse model was established by inducing unilateral ischemia on the left hindlimbs of ICR mice after femoral artery ablation. Seven days after inducing ischemia, [(18)F]5 was administered to the mice through the tail vein. Ischemic muscle uptake of [(18)F]5 was significantly higher than that of normal muscle (P<.01). Specific uptake was confirmed by coinjection of 1 with [(18)F]5. Here, we successfully labeled RGD peptide with (18)F via hydrazone formation between 3 and 4, resulting to [(18)F]5. [(18)F]5 was found to have high affinity for alpha(v)beta(3)-integrin and to accumulate specifically in ischemic hindlimb muscle of mice. We suggest that (18)F labeling via formation of hydrazone between HYNIC peptide and [(18)F]4 is a useful method for labeling c(RGDyK), which can be applied for imaging angiogenesis.

Animals↗

PubMed2006

The neural correlates of cross-modal interaction in speech perception during a semantic decision task on sentences: a PET study.

Speech perception in face-to-face conversation involves processing of speech sounds (auditory) and speech-associated mouth/lip movements (visual) from a speaker. Using PET where no scanner noise was present, brain regions involved in speech cue processing were investigated with the normal hearing subjects with no previous lip-reading training (N = 17) carrying out a semantic plausibility decision on spoken sentences delivered in a movie file. Multimodality was ensured at the sensory level in all four conditions. Sensory-specific speech cue of one sensory modality, i.e., auditory speech (A condition) or mouth movement (V condition), was delivered with a control stimulus of the other modality whereas speech cues of both sensory modalities (AV condition) were delivered during bimodal condition. In comparison to the control condition, extensive activations in the superior temporal regions were observed bilaterally during the A condition but these activations were reduced in extent and left lateralized during the AV condition. Polymodal region such as left posterior superior temporal sulcus (pSTS) involved in cross-modal interaction/integration of audiovisual speech was found to be activated during the A and more so during the AV conditions but not during the V condition. Activations were observed in Broca's (BA 44), medial frontal (BA 8), and anterior ventrolateral prefrontal (BA 47) regions in the left during the V condition, where lip-reading performance was less successful. Results indicated that the speech-associated lip movements (visual speech cue) rendered suppression on the activity in the right auditory temporal regions. Overadditivity (AV > A + V) observed in the right postcentral region during the bimodal condition relative to the sum of unimodal speech conditions was also associated with reduced activity during the V condition. These findings suggested that visual speech cue could exert an inhibitory modulatory effect on the brain activities in the right hemisphere during the cross-modal interaction of audiovisual speech perception.

Adult↗

PubMed2006

Intercellular adhesion molecule-1 is upregulated in ischemic muscle, which mediates trafficking of endothelial progenitor cells.

BACKGROUND: Trafficking of transplanted endothelial progenitor cells (EPCs) to an ischemic organ is a critical step in neovascularization. This study was performed to elucidate the molecular mechanism of EPC trafficking in terms of adhesion molecules. METHODS AND RESULTS: Using murine hindlimb ischemia model, we examined expressions of E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in ischemic muscle by immunofluorescence. ICAM-1 was overexpressed in ischemic muscle compared with nonischemic muscle, whereas expressions of E-selectin, VCAM-1, and PECAM-1 did not show that much difference. ICAM-1 was also upregulated by hypoxia in murine endothelial cells (ECs) as assessed by immunoblot and flow cytometry. EPCs were attached to ECs specifically through ICAM-1/beta-2 integrin interaction in vitro. When EPCs were labeled with fluorescent dye or radioisotope (Tc-99m-HMPAO) and systemically administrated in vivo, EPCs preferentially homed to ischemic muscle. By blocking ICAM-1, EPCs entrapment to ischemic limb in vivo was significantly reduced and neovascularization induced by EPC transplantation was attenuated. CONCLUSIONS: ICAM-1 is upregulated by ischemia, and this is closely associated with EPCs entrapment to ischemic limb. Our findings suggest that ICAM-1 expression might be important in regulating the process of neovascularization through its ability to recruit EPCs.

Animals↗

PubMed2006

In vivo monitoring of DNA vaccine gene expression using firefly luciferase as a naked DNA.

The administration of naked DNA into animals is increasing as a research tool to develop DNA vaccine. To monitor the distribution and duration of gene expression of a DNA vaccine in living organisms, we used the naked DNA encoding firefly luciferase (Fluc) as an imaging reporter gene, and evaluated in vivo bioluminescent images in a murine model. We observed bioluminescence at the injection site and at inguinal lymph node from 10h to 24h post-injection when DNA vaccine encoding Fluc (pcDNA3.1-Fluc) was injected into the bilateral posterior flanks in mice. Fluc gene expressions at injection sites and unilateral posterior flank inguinal lymph node were also confirmed by RT-PCR. However, when pcDNA3.1-Fluc was injected into the mid-dorsum bioluminescent signals were observed at the injection site for up to 14 days post-injection, but no bioluminescent signals were detected in inguinal lymph nodes. Concurrent mRNA expressions of Fluc gene at injection sites but not at inguinal lymph nodes were confirmed by RT-PCR. These findings suggest that optical imaging using Fluc could be useful for monitoring the location, intensity and duration of gene expression of naked DNA vaccines in living animals non-invasively and repetitively.

Animals↗

PubMed2006

In vivo imaging of adenovirus transduction and enhanced therapeutic efficacy of combination therapy with conditionally replicating adenovirus and adenovirus-p27.

Gene therapy is hampered by poor gene transfer to the tumor mass. We previously proposed a combination adenoviral gene therapy containing a conditionally replicating adenovirus (CRAD) expressing mutant E1 (delta24RGD) and a replication-defective E1-deleted adenovirus to enhance the efficiency of gene transfer. Mutant E1 expressed by delta24RGD enables the replication of replication-defective adenoviruses in tumors when cancer cells are co-infected with both viruses. In this study, gene transfer rates in xenografts tumors were monitored by bioluminescence in cells infected with the replication-defective adenovirus-luciferase (ad-luc). Tumor masses treated with CRAD + ad-luc showed dramatically stronger and more prolonged luciferase expression than ad-luc-treated tumors and this expression spread through the entire tumor mass without significant systemic spread. Transduction with CRAD + replication-defective adenovirus-p27 increased the expression of p27 by 24-fold versus transduction with ad-p27 alone. Treatment of a lung cancer cell line and of established lung cancer xenografts with CRAD + adenovirus-p27 also induced stronger growth suppression than treatment with either virus alone. These findings confirm the selective replication of E1-deleted adenovirus containing a therapeutic gene due to the presence of mutant E1 produced by delta24RGD in tumors. Moreover, this replication increased the therapeutic gene transfer rate and enhanced its antitumor effects.

Adenoviridae↗

PubMed2006

The clinical impact of 18F-FDG PET in papillary thyroid carcinoma with a negative 131I whole body scan: a single-center study of 108 patients.

OBJECTIVE: To assess whether FDG PET could localize the recurrent or metastatic lesions in papillary thyroid cancer patients with negative radioiodine scan. METHODS: Whole body PET was performed after injecting 370-555 MBq of 18F-FDG in 108 patients, who were suspected of having recurrence or metastasis and whose 131I whole body scans were negative. Recurrence or metastasis occurred in 63 patients by pathology or clinical assessment, whereas 45 patients remained in remission. RESULTS: FDG PET revealed recurrence or metastases in 59 patients (sensitivity 93.7%), whereas thyroglobulin (Tg) levels were elevated in 41 (sensitivity 65.1%). In 35 of 45 patients in remission, FDG PET was negative (specificity 77.8%). When patients positive for antithyroglobulin antibody were excluded, the sensitivity and specificity of serum Tg became 84.8% and 46.9%, respectively. Compared to Tg measurement, FDG PET detected more metastatic lesions in cervical lymph nodes. Of 40 patients with a negative radioiodine scan showing diffuse hepatic uptake, metastases occurred in 23 patients and remission in 17. FDG PET showed 100% sensitivity and 76.5% specificity in the detection of recurrence in these 40 patients. CONCLUSION: FDG PET is useful for localizing recurrent or metastatic lesions in 131I scan-negative thyroid cancer patients. In particular, it is superior to serum Tg measurement for identifying metastases to cervical lymph nodes. We recommend its use in cases of negative radioiodine scan with diffuse hepatic uptake.

Adult↗

PubMed2006

Synthesis and evaluation of benzothiophene derivatives as ligands for imaging beta-amyloid plaques in Alzheimer's disease.

The imaging of the distribution of beta-amyloid (Abeta) plaques in the brain is becoming an important diagnostic modality in Alzheimer's disease (AD). Here, we synthesized novel benzothiophene derivatives and labeled them with (18)F for the potential diagnostic imaging of AD patients using positron emission tomography. The K(i) values of benzothiophene derivatives were evaluated by competitive binding assay using 2-(3'-[(125)I]iodo-4'-N-methylaminophenyl)benzothiazole as a radioligand and Abeta(1-40) or Abeta(1-42) aggregates as receptors. All synthesized benzothiophene derivatives showed high binding affinities (K(i)=0.28-6.50 nM) to both Abeta(1-40) and Abeta(1-42) aggregates. Binding affinities were increased by O-alkylation or N-alkylation of 2-(4'-hydroxyphenyl)benzothiophene or 2-(4'-aminophenyl)benzothiophene. Biodistribution studies of 2-(4'-O-(2''-[(18)F]fluoroethyl)hydroxyphenyl)benzothiophene ([(18)F]) and 2-(4'-O-(3''-[(18)F]fluoropropyl)hydroxyphenyl)benzothiophene ([(18)F]) in normal mice were performed after intravenous injection through the tail vein. In biodistribution data, [(18)F] and [(18)F] showed high initial brain uptakes at 2 min (5.2+/-0.4% and 3.3+/-0.2% ID/g, respectively), and brain activities washed out to 2.0+/-0.2% and 0.5+/-0.1% ID/g at 4 h, respectively. In conclusion, benzothiophene derivatives showed excellent binding affinities for Abeta aggregates and high initial brain uptakes in normal mice.

Alzheimer Disease↗

PubMed2006

Effect of all-trans retinoic acid on sodium/iodide symporter expression, radioiodine uptake and gene expression profiles in a human anaplastic thyroid carcinoma cell line.

The plasma membrane glycoprotein sodium/iodide symporter (NIS) is crucial for thyroid hormone biosynthesis and mediates the iodide uptake of thyrocytes. It has been shown that retinoic acid (RA) alters NIS gene expression in thyroid carcinoma lines and stimulates their iodide uptake. Here, we generated an ARO human thyroidal cancer cell line that expresses the NIS gene (ARO-NIS) and found that its baseline 125I uptake was threefold higher than that of its parental ARO cells. However, a 1-microM all-trans retinoic acid (tRA) treatment significantly increased this 125I uptake up to approximately approximately 6.5-fold on Day 3. tRA also elevated NIS mRNA expression in ARO-NIS cells, with peaks of expression being observed on Day 3. To investigate the underlying genomic mechanisms involved in these tRA-induced phenotypic changes, we subjected tRA-treated and untreated ARO-NIS cells to cDNA microarray analysis. Of 1152, genes spotted onto the microarray membrane, 18 were up-regulated (z ratio>2.0) and 33 were down-regulated (z ratio<-2.0) in ARO-NIS cells after 3 days of tRA treatment. More specifically, tRA increased the expression of BCL3, CSRP3, v-fos, and CDK5 genes and decreased the expression of the FGF12 and IGFBP6 genes. Thus, tRA treatment of human anaplastic thyroid carcinoma cells stably expressing the NIS gene significantly elevates their NIS-mediated radioiodine uptake and alters the expression of many genes involved in cell growth and cellular differentiation. Therefore, tRA treatment and NIS gene transfection are potential tools for the diagnosis and treatment of thyroid cancer.

Carcinoma↗

PubMed2006

Evaluation of transcriptional activity of the oestrogen receptor with sodium iodide symporter as an imaging reporter gene.

BACKGROUND: Oestrogen receptors are ligand-dependent transcription factors whose activity is modulated either by oestrogens or by an alternative signalling pathway. Oestrogen receptors interact via a specific DNA-binding domain, the oestrogen responsive element (ERE), in the promoter region of sensitive genes. This binding leads to an initiation of gene expression and hormonal effects. OBJECTIVE: To determine the transcriptional activity of the oestrogen receptor, we developed a molecular imaging system using sodium iodide symporter (NIS) as a reporter gene. METHODS: The NIS reporter gene was placed under the control of an artificial ERE derived from pERE-TA-SEAP and named as pERE-NIS. pERE-NIS was transferred to MCF-7, human breast cancer cells, which highly expressed oestrogen receptor-alpha with lipofectamine. Stably expressing cells were generated by selection with G418 for 14 days. After treatment of 17beta-oestradiol and tamoxifen with serial doses, the (125)I uptake was measured for the determination of NIS expression. The inhibition of NIS activity was performed with 50 micromol x l(-1) potassium perchlorate. RESULTS: The MCF7/pERE-NIS treated with 17beta-oestradiol accumulated (125)I up to 70-80% higher than did non-treated cells. NIS expression was increased according to increasing doses of 17beta-oestradiol. MCF7/pERE-NIS treated with tamoxifen also accumulated (125)I up to 50% higher than did non-treated cells. Potassium perchlorate completely inhibited (125)I uptake. When MDA-MB231 cells, the oestrogen receptor-negative breast cancer cells, were transfected with pERE-NIS, (125)I uptake of MDA-MB-231/pERE-NIS did not increase. CONCLUSION: This pERE-NIS reporter system is sufficiently sensitive for monitoring transcriptional activity of the oestrogen receptor. Therefore, cis-enhancer reporter systems with ERE will be applicable to the development of a novel selective oestrogen receptor modulator with low toxicity and high efficacy.

Breast Neoplasms↗

PubMed2006

Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction.

UNLABELLED: Adult stem cell therapy is expected to improve left ventricular function in patients with myocardial infarction. Because of the low risk of arrhythmia and the maximal concentration at the target tissue, intracoronary infusion of stem cells is preferred. The aim of this study was to investigate the homing and tissue distribution of intracoronary injected peripheral hematopoietic stem cells labeled with 18F-FDG. METHODS: Seventeen patients with myocardial infarction were included as the intracoronary injection group (14 males, 3 females; age, 58 +/- 12 y). Three patients underwent intravenous stem cell injection as the intravenous injection group (3 males, 0 females; age, 50 +/- 20 y). After mobilization with granulocyte colony-stimulating factor (G-CSF), peripheral stem cells were collected by means of apheresis. 18F-FDG labeling of stem cells was performed for 40 min with gentle intermittent mixing at 37 degrees C. The mean labeling efficiency was 72% (range, 46%-95%), and 44.4-175 MBq (1.2-5 mCi) of 18F-FDG-labeled stem cells were injected via an intracoronary catheter after stenting in infarct-related arteries. PET/CT images were obtained with a 3-dimensional acquisition mode 2 h after intracoronary infusion. RESULTS: Two hours after intracoronary infusion, 1.5% (range, 0.2%-3.3%) of injected stem cells accumulated at the infarcted myocardium. Outside of the myocardium, spleen, liver, bladder, and bone marrow showed a high stem cell accumulation. The delayed image of a patient up to 20 h showed a prolonged residence of stem cells at the myocardium. Intravenous injection of stem cells showed a high initial lung uptake with no myocardial activity. CONCLUSION: We have shown that 18F-FDG-labeled stem cell PET could be used to assess the tissue distribution and to measure the amount of stem cells at a target tissue. 18F-FDG-labeled stem cell PET can be used to measure and optimize the amount of stem cells injected.

Adult↗