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We tried to develop a dual-modal PET/MR imaging probe using a straightforward one-pot method by encapsulation with specific amphiphiles. In this study, iron oxide (IO) nanoparticles were encapsulated with three amphiphiles containing PEG, DOTA and the prostate-specific membrane antigen (PSMA)-targeting ligand in aqueous medium. The diameter of the prepared nanoparticle DOTA-IO-GUL was 11.01±1.54nm. DOTA-IO-GUL was labeled with 68 Ga in high efficiency. The DOTA-IO-GUL showed a dose-dependent binding to LNCaP (PSMA positive) cells via a competitive binding study against 125 I-labeled MIP-1072 (PSMA-targeting agent). Additionally, PET and MR imaging results showed PSMA selective uptake by only 22Rv1 (PSMA positive) but not PC-3 (PSMA negative) in dual-tumor xenograft mouse model study. MR imaging showed high resolution, and PET imaging enabled quantification and confirmation of the specificity. In conclusion, we have successfully developed the specific PSMA-targeting IO nanoparticle, DOTA-IO-GUL, as a dual-modality probe for complementary PET/MR imaging. From the Clinical Editor The combination of using Positron Emission Tomography (PET) and computed tomography (CT) in clinical practice is now the norm. With advances in technology, the next step would be to develop combined PET and Magnetic Resonance (MR) dual-imaging. In this article, the authors described their positive study on the development of a dual-modal PET/MR imaging probe using a prostate cancer model.

Radiolabeled nitroimidazole (NI) derivatives have been extensively studied for imaging hypoxia. To increase the hypoxic tissue uptake, we developed (68)Ga-labeled agents based on mono-, bis-, and trisnitroimidazole conjugates with the chelating agent 1,4,7-triazacyclononane-1,4,7-tris[methyl(2-carboxyethyl)phosphinic acid] (TRAP). All the three agents showed high radiolabeling yields (>96%) and were found to be stable up to 4h in prepared medium at room temperature and in human serum at 37°C. The trivalent agent showed a significant increase in hypoxic to normoxic uptake ratio (p

Introduction:The purpose of this study was to evaluate the predictive role of quantitative metabolic parameters using total lesion glycolysis (TLG) in 18F-2-fluoro-2-deoxyglucose-positron emission tomography/computed tomography for developing gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer (NSCLC) patients treated with first-line gefitinib.Methods:A total of 75 NSCLC patients harboring activating EGFR mutation and receiving first-line gefitinib were analyzed. Whole-body 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography scans were acquired before first-line gefitinib. The maximal standardized uptake value and TLG of all lesions were calculated. Maximal standardized uptake value and TLG were categorized using the tertile cutoff. Treatment outcomes were compared between groups.Results:Overall response rate of gefitinib was 69.4%, and median progression-free survival (PFS) of gefitinib was 11.5 months. Overall response rates were similar between low, intermediate, and high TLG groups (68.0% versus 76.0% versus 68.0%, p = 0.274). However, PFS significantly differed by TLG groups, and high TLG was associated with shorter PFS (7.2 months in high TLG; 11.9 months in intermediate TLG; and 24.2 months in low, p < 0.001). Multivariate models adjusted for disease status and response to gefitinib showed that TLG was an independent predictive factor for PFS. TLG was also significantly associated with overall survival (p = 0.005).Conclusion:TLG can predict PFS and development of gefitinib resistance in EGFR-mutant NSCLC patients treated with first-line gefitinib. Baseline metabolic tumor burdens measured with TLG before first-line gefitinib will be of great help in predicting time to acquired resistance.

Introduction A lipiodol solution of 188 Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (HTDD) has been successfully developed for liver cancer therapy; however, its preparation requires a multi-step synthesis and it is characterized by a low labeling yield. Methods We synthesized a new compound, 4-hexadecyl-4,7-diaza-1,10-decanedithioacetate (AHDD), without gem dimethyl groups to address these issues. AHDD was formulated into a kit and was labeled with 188 Re. Biodistribution study was performed using normal BALB/c mice. Results The kit was labeled with 188 Re with a high efficiency (98.8±0.2%). After extraction with lipiodol, the overall yield of 188 Re-HDD/lipiodol was as high as 90.2±2.6%. A comparative biodistribution study of 188 Re-HTDD and 188 Re-HDD was performed in normal mice after intravenous injection. The lungs were identified as the main uptake site due to capillary-blockage. 188 Re-HDD/lipiodol showed a significantly higher lung uptake than that of 188 Re-HTDD/lipiodol (p Conclusion The newly synthesized 188 Re-HDD/lipiodol showed improved radiolabeling yield and biodistribution results compared to 188 Re-HTDD/lipiodol, and may therefore be more suitable for liver cancer therapy.

Introduction Positron emission tomography (PET) may provide more accurate quantification of kidney function such as glomerular filtration rate (GFR) than gamma imaging. The purpose of these experiments was to prepare and evaluate Ga-68 complexes as potential PET agents for measurement of GFR. Methods We labeled EDTA, DTPA, DOTA, and NOTA with Ga-68 obtained from a Ge-68/Ga-68-generator and measured the binding to serum and red blood cells. Biodistribution study was performed in male BALB/c mice after intravenous injection together with Cr-51-EDTA as the standard for glomerular filtration rate (GFR) measurement. Animal-PET study was performed using BALB/c mice. Results All the tested chelating agents except DTPA showed quantitative labeling yields (> 99%). Among them, Ga-68-NOTA showed consistently low binding to both human and mouse RBC and serum protein. Biodistribution study showed no significant difference between Ga-68-NOTA and Cr-51-EDTA groups by one-way analysis of variance (ANOVA) (p > 0.05). Furthermore, the GFR values obtained by Ga-68-NOTA and Cr-51-EDTA were almost same (0.26 ± 0.04 and 0.25 ± 0.04 mL/min, respectively). Animal-PET study showed almost the same GFR (0.25 mL/min) with the values obtained by biodistribution study. Conclusion We proved that an easy-to-prepare agent Ga-68-NOTA is ideal for renal PET as well as for GFR measurement.

Background/aim Recently, a novel circulatory system, the primo vascular system (PVS), was found to be a potent metastatic route of cancer cells. The aim of the current work is to demonstrate that cancer cells injected into the testis migrate through the primo vessel (PV). Materials and methods NCI-H460 cells labeled with fluorescent nanoparticles (FNP) or green fluorescent protein (GFP) gene transfection were injected into testicular parenchyma in 24 rats. After 24 hours of injection, the abdominal cavity was investigated via a stereomicroscope, to detect the PVS, and the samples were analyzed histologically with 4′,6-diamidino-2-phenylindole (DAPI) and hematoxylin and eosin. Results Injected cancer cells were detected inside the PVS distributed on the abdominal organs. Some were detected inside intestinal parenchyma into which the attached primo vessels (PVs) entered. Conclusion The results supported the fact that the PVS may be a novel migration path of cancer cells, in addition to the lymphatic and hematogenous routes.

We show here, that the proapoptotic peptide, KLAKLAKKLAKLAK (KLA), which by itself does not penetrate cell membranes, can do so when fused to a protein transduction domain derived from NH2-terminus of translationally controlled tumor protein (TCTP-PTD, MIIYRDLISH). Once inside the cell, the conjugated KLA exerts its proapoptotic activity to inhibit tumor growth. We evaluated the cellular uptake of KLA fused to TCTP-PTD (hereafter called TCTP-KLA) and its effect on cancer cell viability. The IC50 of TCTP-KLA was between 7 and 10 μmol/L. We also evaluated its anti-tumor activity in vivo by injecting it into xenografts of lung carcinoma in Balb/c nude mice. Tumor growth inhibition resulting from treatment with TCTP-KLA was better than that of TAT-KLA. These results suggest that TCTP-KLA can be applied to design cancer therapeutics.

In this study, we developed a combination therapy (pcDNA3/hMUC1+mANT2 shRNA) to enhance the efficiency of MUC1 DNA vaccination by combining it with mANT2 short hairpin RNA (shRNA) treatment in immunocompetent mice. mANT2 shRNA treatment alone increased the apoptosis of BMF cells (B16F1 murine melanoma cell line coexpressing an MUC1 and Fluc gene) and rendered BMF tumor cells more susceptible to lysis by MUC1-associated CD8(+) T cells. Furthermore, combined therapy enhanced MUC1 associated T-cell immune response and antitumor effects, and resulted in a higher cure rate than either treatment alone (pcDNA3/hMUC1 or mANT2 shRNA therapy alone). Human MUC1 (hMUC1)-loaded CD11c(+) cells in the draining lymph nodes of BMF-bearing mice treated with the combined treatment were found to be most effective at generating hMUC1-associated CD8(+)IFNγ(+) T cells. Furthermore, the in vitro killing activities of hMUC1-associated cytotoxic T cells (CTLs) in the combined therapy were greater than in the respective monotherapies. Cured animals treated with the combined treatment rejected a rechallenge by BMF cells, but not a rechallenge by B16F1-Fluc cells at 14 days after treatment, and showed MUC1 antigen-associated immune responses. These results suggest that combined therapy enhances antitumor activity, and that it offers an effective antitumor strategy for treating melanoma.

The imaging of hypoxia is important for therapeutic decision making in various diseases. (68)Ga is an important radionuclide for positron emission tomography (PET), and its usage is increasing, due to the development of the (68)Ge/(68)Ga-generator. In the present study, the authors synthesized two nitroimidazole derivatives by conjugating nitroimidazole and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an amide bond (4) and a thiourea bond (5). Both derivatives were labeled with (68)Ga with high labeling efficiency and were stable after labeling. The low partition coefficients (logP) of (68)Ga-4 (-4.6) and (68)Ga-5 (-4.5) demonstrated the hydrophilic natures of the derivatives, and both showed higher uptake in cancer cell lines cultured under hypoxic condition than under normoxic condition. However, (68)Ga-5 showed higher liver uptake than (68)Ga-4 in a biodistribution study due to higher lipophilicity. In an animal PET study, (68)Ga-4 showed higher standard uptake values (SUV) in tumors than (68)Ga-5 in mice xenografted with CT-26 mouse colon cancer cells.

Calculation of a specific rate constant (k) and activation energy (Ea) of 18F-labeling reaction is important to obtain objective data. However, it has never been tried, because short time heating required for the calculation of the parameters was difficult. In the present study, we could calculate the parameters using combination of coat-capture–elution method (Aerts et al.) and microfluidic processes. The Ea values obtained for Ts-naphthol in acetone, MeCN and t-BuOH were 5.83, 8.98, and 13.54 kcal/mol, respectively, and for Ms-naphthol in the same solvents were 5.81, 8.16, and 19.34 kcal/mol, respectively. Calculation of these parameters might be useful for setting up [18F]fluorination procedure and for developing new precursors.

(68)Ga PET imaging in clinical oncology represents a notable development because the availability of (68)Ga is not dependent on a cyclotron. Furthermore, labeled amino acid derivatives have been proven to be useful for the imaging many tumor types. In the present study, we synthesized β-aminoalanine, γ-aminohomoalanine, and lysine conjugates of macrocyclic bifunctional chelating agents, such as, NOTA (1a-c) and DOTA (2a-c). The compounds produced were found to be potential useful as (68)Ga-PET imaging agents. In particular, they showed high tumor uptakes in vitro and in vivo, and had high labeling yields and excellent stabilities. The co-ordination chemistry of NOTA-monoamide compound 1a was studied by multinuclear NMR. In vitro studies showed that the synthesized compounds were taken up by cancer cells more than controls ((68)Ga-NOTA and (68)Ga-DOTA). Furthermore, in vivo studies showed that they have high tumor to muscle and tumor to blood ratios, and small-animal PET imaging revealed high tumor uptakes as compared with other organs, and high bladder activities, indicating rapid renal excretion. These results might motivate the use of (68)Ga amino acid PET for tumor diagnosis.

Introduction Tris(4,6-dimethoxysalicylaldimine)- N , N ′-bis(3-aminopropyl)- N , N ′-ethylenediamine (BAPEN), a tris(salicylaldimine) derivative, is a heart positron emission tomography (PET) agent when labeled with 68 Ga. However, its labeling requires complicated and time-consuming procedures. In this study, the authors formulated a new BAPEN kit for convenient 68 Ga labeling. Methods BAPEN (0.25 mg) kits were prepared by dispensing its solution in 1 M sodium acetate buffer (pH 5.5) into sterile vials and lyophilization. The prepared kits were labeled with generator-eluted 68 Ga in 0.1 N HCl. Stability in human serum was tested. Expiration date was determined by accelerated testing according to US Food and Drug Administration guidelines. A Biodistribution study was performed in normal mice after injection via tail vein. Results The prepared kits achieved radiolabeling efficiencies in excess of 95% and showed a shelf-life of 98 days at 25°C and 64.3 months at 4°C. 68 Ga-BAPEN was found to be stable in human serum at 37°C for at least 1 h. Furthermore, a biodistribution study revealed high heart uptake (10.8% ID/g, 1 h). Conclusions The authors developed a BAPEN kit for convenient labeling with 68 Ga. The 68 Ga-BAPEN showed high stability and excellent biodistribution results in normal mice, which is required for myocardial PET imaging.

FDG uptake mediated by glucose transporter type 1 (Glut-1) and tumor proliferative activity assessed by Ki-67 expression provide prognostic information in patients with non-small-cell lung cancer (NSCLC). Here, we compared the prognostic significances of FDG uptake, and of Glut-1 and Ki-67 expressions in patients with NSCLC.NSCLC patients (n=53, F:M=16:37, age 61.9+/-12.1 years) who underwent curative resection after FDG-PET were enrolled. Thirty-one patients had stage I, 15 stage II, and 7 stage III disease. Patients were treated by surgery only (n=12), surgery plus adjuvant oral chemotherapy (n=32), or surgery plus adjuvant intravenous chemo- or radio-therapy (n=9). Maximum standardized FDG uptake values (maxSUV), and the Glut-1 and Ki-67 expressions of resected tumors were analyzed for correlations and relations with tumor recurrence. The median follow-up duration was 15 months.Thirteen (24.5%) of the 53 patients experienced recurrence during a median follow-up of 8 months and significant correlations were found between maxSUV, Glut-1, and Ki-67 expressions (r=0.48-0.79, p0.001). Univariate analysis revealed that disease-free survival (DFS) was significantly correlated with maxSUV (7 versusor =7, p=0.001), % Ki-67 expression (25% versusor =25%, p=0.047), tumor size (3 cm versusor =3 cm, p=0.027), and tumor cell differentiation (well/moderate versus poor, p=0.011). However, multivariate Cox proportional analysis identified maxSUV as the only determinant of DFS (p=0.005). Patients with a maxSUV ofor =7 (n=14) had a significantly lower 1-year DFS rate (57.1%) than those with a maxSUV of7 (n=39, 89.7%).FDG uptake is more valuable than Glut-1 or Ki-67 expression in terms of predicting prognosis in patients with resected NSCLC.

FDG uptake in NSCLC is related to glucose transporter type 1 (Glut-1) expression. Here, we investigated the direct causal relationship between FDG uptake and Glut-1 expression to determine the role of Glut-1 in FDG uptake by malignant and benign lymph nodes (LNs).Fifty-five curative lung resections in 53 NSCLC patients (male:female=36:17, age=62.0+/-11.8 years) were included. Maximum standardized uptake values (maxSUVs) of LNs in preoperative whole body FDG-PET and Glut-1 immunostaining results were compared.Of 316 pathologically confirmed LNs, 12.3% (39/316) were malignant, and in malignant LNs, FDG positive LNs were no different from FDG negative LNs in terms of size (15.0+/-6.7 mm vs 10.0+/-6.1mm, p0.05), or in terms of the proportion of LNs occupied by tumor (60.0+/-28.8% vs 39.2+/-38.4%, p0.05), but had greater percentages of Glut-1 positive cells in tumors (74.1+/-31.8% vs 22.7+/-18.7%, p0.01), and Glut-1 staining intensities (3.4+/-0.9 vs 1.8+/-1.3, p0.01). FDG negative malignant LNs featured cytoplasmic Glut-1 expression and adenocarcinoma. Glut-1 staining intensities were found to be significantly correlated with the maxSUVs of malignant LNs (rho=0.516, p0.05), but the percentages of Glut-1 positive cells in tumors were not (r=0.2072, p0.05). Analysis of FDG positive benign LNs showed that maxSUV was not correlated with degree of follicular hyperplasia, or Glut-1 expression (p0.05).Intense Glut-1 immunoreactivity was found to be proportionally related to the degree of FDG uptake by malignant LNs in NSCLC. However, the finding that Glut-1 expression in lymphoid hyperplasia showed no correlation with FDG uptake in benign LNs requires further investigation.

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

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 (F luc ) 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 10 h to 24 h post-injection when DNA vaccine encoding F luc (pcDNA3.1-F luc ) was injected into the bilateral posterior flanks in mice. F luc gene expressions at injection sites and unilateral posterior flank inguinal lymph node were also confirmed by RT-PCR. However, when pcDNA3.1-F luc 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 F luc gene at injection sites but not at inguinal lymph nodes were confirmed by RT-PCR. These findings suggest that optical imaging using F luc could be useful for monitoring the location, intensity and duration of gene expression of naked DNA vaccines in living animals non-invasively and repetitively.

Iodide uptake occurs across the membrane of thyroid cells via an active transporter, sodium/iodide symporter (NIS). Decreased NIS expression levels account for the reduced iodide uptake in thyroid carcinomas. We found that thyroid cancer patients with positive immunostaining for NIS responded to I-131 therapy better than did the patients with negative immunostaining. Thus, NIS gene can be used for radionuclide gene therapy. Targeted expression of functional NIS in cancer cells would enable these cells to concentrate iodide from plasma and would, therefore, offer the possibility of radioiodine therapy. We and others have shown that gene transfer of NIS into a variety of cell types confers increased radioiodine uptake up to several hundred-fold that of controls. Imaging reporter gene is useful in noninvasively determining the location, duration and magnitude of transgene expression in living animal. We could monitor not only exogenous gene expression, but also endogenous gene expression such as p53 and nuclear receptor activity such as retinoic acid receptor using cis-NIS reporter imaging gene system. This reporter gene imaging can also be used for monitoring cancer cells, stem cells and immune cells. In conclusion, the NIS has the potential to expand molecular nuclear medicine in the near future.

For homogeneous delivery of beta radiation to skin cancer, we developed a simple method for preparing (188) Re-labeled nitrocellulose paper. The homogeneity and stability of the labeled paper were investigated. Absorbed dose estimates were calculated using the Monte-Carlo method. A 74-MBq (188) Re-labeled paper with 1-cm diameter delivered 147.2 Gy up to 1-mm depth after 2-h irradiation. Animal experiments on tumor-bearing mice showed that 50 Gy is an adequate dose for treating skin cancer. Tumors disappeared 7 days after irradiation in all the groups irradiated by 50 or 100 Gy. The (188) Re-labeled paper provided a convenient, economical, effective, and non-invasive method of treating skin cancer.

Diaminedithiol (DADT) or N -monosubstituted DADT is known to form lipophilic neutral chelates with technetium. As a result, they are used for brain imaging agents. However, 99m Tc- N , N ′-dimethylDADT has been demonstrated to have a positive charge and a lower lipophilicity (log P=0.1) in this experiment. The results of a biodistribution study showed that most activity was found in the intestine after 1 hr, which is the evidence of bile excretion. Increased heart-uptake in mice suggests that this compound or its derivatives can be used as a myocardial-imaging agent.

We have designed the gene delivery carrier targeted to Molt 4 cells, human leukemia T cells, using monoclonal antibody against leukemia-specific JL1 antigen, anti-JL1 antibody, as a targeting moiety. Anti-JL1 antibody has been proven to bind to JL1 antigen and subsequently be internalized into Molt 4 cells, demonstrating that anti-JL1 antibody has the potential as a targeting ligand for leukemia-specific gene transfer. Anti-JL1 antibody was modified with the heterobifunctional crosslinker, PDPH, at carbohydrate sites and conjugated to thiolated poly- l -lysine (PLL) via disulfide bridges. The composition and antigen binding affinity of antibody–PLL conjugates were analyzed by the amino acid analysis and the flow cytometry, respectively. Antibody–PLL conjugates neutralized pSV-β-galactosidase plasmid DNA at 5:1 weight ratio and condensed into about 200–300-nm complexes. DNA/antibody–PLL complexes were effectively internalized into Molt 4 cells after 4 h incubation at 37°C and showed significantly higher in vitro transfection efficiency than DNA/PLL complexes and DNA/Lipofectin™ formulation due to the targeting effect of receptor-mediated endocytosis induced by anti-JL1 antibody.

Radiolabeled lipiodol has been used for targeting liver cancer. We developed a lipiodol solution of (188)Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol) and investigated its feasibility for the treatment of liver cancer. The lipiodol solution of (188)Re-TDD was well-retained in the lipiodol phase in vitro. After injection through the tail veins of mice, high lung-uptake was investigated which is evidence of embolizing activity. We also found high accumulation in hepatoma after injection through the hepatic arteries of hepatoma-bearing rats. In conclusion, the lipiodol solution of (188)Re-TDD is a promising agent for liver cancer therapy.

The pattern and intensity of F-18-FDG uptake in the gastrointestinal (GI) tract are variable and can often cause confusion. The purpose of this study was to evaluate the relationship between GI tract symptoms and GI uptake of F-18-FDG. We evaluated whole-body FDG-PET of 314 persons (M:F = 147:167; 13-83 years) in whom pathologic GI tract disorders had not been observed. Uptake score and pattern were evaluated visually. Symptoms were grouped as follows: diarrhea, constipation, and neither diarrhea nor constipation. Among symptom groups, there was no statistically significant difference in FDG uptake score. But intense FDG uptake with focal pattern, which can cause confusion, was observed more frequently in the descending colon of patients with constipation than in those with diarrhea or without GI symptoms. When focal intense FDG uptake is observed in the abdomino-pelvic area, stricter attention to GI symptoms would improve the specificity of whole-body FDG-PET.

The purpose of this study was to compare whole-body fluorine-18-fluorodeoxyglucose positron emission tomography (F-18 FDG-PET) with conventional imaging modalities (CI: CT/MRI) in the detection of recurrent head and neck cancer. Whole-body F-18 FDG-PET was performed in 45 patients (recurrence = 39; no recurrence = 16) with previous head and neck cancer. We compared detectability by the period from initial cancer treatment and treatment modalities. Thirty were PET-positive and 15 were PET-negative. The sensitivity, specificity, and accuracy of PET were 97%, 88%, and 93%, respectively (corresponding figures of CI were 73%, 85%, and 77%). In 18 patients who underwent PET less than 3 months after the completion of cancer treatment, the sensitivity, specificity, and accuracy were 100%, 86%, and 94%, while for CI, the corresponding figures were 67%, 71%, and 69%. In 18 patients who had undergone surgery, PET results were 14 true positive and 4 were true negative; significantly higher detectability than CI. Among the patients who were evaluated for more than 6 months or treated by radiotherapy without surgery, diagnostic accuracy was almost the same. Whole body F-18 FDG-PET was a valuable tool in the evaluation of post-therapeutic recurrence of head and neck cancer.

Objective. We report the establishment and characterization of three new cell lines derived from uterine malignant mixed mullerian tumor (MMMT). Methods. Three uterine MMMT cell lines from primary tumors of Korean patients were cultured and the involved cell morphology, growth properties, DNA profiles, immunohistochemical properties, tumor-associated antigen secretion, and genetic alterations of related oncogenes and tumor suppressor genes were studied as well. Results. Three MMMT cell lines were successfully established including one homologous tumor SNU-539 and two heterologous tumors SNU-685 and SNU-1077. All lines showed substrate adherence and high viability and were proven by DNA fingerprinting analysis to be unique. Contamination by mycoplasma and bacteria was excluded. SNU-539 and SNU-1077 cells stained positively for both epithelial and mesenchymal antigens, while SNU-685 cells only stained positively for mesenchymal antigens. The level of secretion of tumor-associated antigens, CA125 and CEA, was shown to be undetectable in all three lines. One missense mutation from AAC to GAC at codon 239 of exon 7 in the p53 gene was identified in SNU-539. Conclusions. These newly established and characterized permanent uterine MMMT cell lines might be regarded as valuable resources for a multitude of in vitro investigations, which should be used for clarifying the obscure histogenetic origin and understanding the biological behavior of this aggressive tumor.

JL1 is a novel thymocyte-differentiated antigen strictly confined to stage II immature cortical thymocytes. It is expressed in several types of leukemias and lymphomas. Murine anti-JL1 monoclonal antibody labeled with 131I and 99mTc showed 60–70% of immunoreactivity and 1.4–1.9 × 109 L/mol of affinity constant. The incubation of the radiolabeled antibody with Molt-4 cells showed no evidence of modulation or shedding. Localization indices increased from day 3 to day 5 in SCID mice bearing Molt-4 cells.

We evaluated the monoclonal antibody CEA-79.4 against carcinoembryonic antigen as an immunoscintigraphic agent for assessing the state of the bone marrow. Western blotting of human granulocyte extracts with the antibody could confirm that the binding was with the epitope of NCA-95. Immunocytochemical staining of bone marrow aspirates revealed specific uptake of this antibody by granulopoietic cells. The affinity constant was 2-9 x 10(9) L/mol. Immunoscintigraphy using 99mTc-labeled CEA-79.4 in a normal volunteer revealed high uptake in the bone marrow as compared to other organs.

and TE2A-Bn-NCS) have different structural features, it is interesting to compare both in terms of in vivo stability and targeting affinity to αvβ3 integrin. In this study we have explored PCB-TE2A and TE2A-Bn-NCS as bifunctional chelating agents by conjugating them with c(RGDyK) peptide, a well validated αvβ3 ligand. Both peptide-conjugates were radiolabeled with Cu and injected into nude mice bearing U87MG xenografts to check their in vivo behavior by biodistribution and PET imaging studies.

Objective The aim of this study was to compare magnetic resonance imaging (MRI) with positron emission tomography/computed tomography (PET/CT) in the preoperative detection of lymph node metastases in patients with uterine cervical cancer. Study Design This retrospective study reviewed patients with cervical cancer who had undergone both preoperative MRI and PET/CT before radical surgery, including lymphadenectomy between 2004–2008. Results Eighty-three patients were identified, of whom 28 (33.7%) had pelvic lymph node metastasis. The sensitivity, specificity, and accuracy for detecting lymph node metastasis were 64.3%, 69.1%, and 67.5% for MRI, and 28.6%, 83.6%, and 65.1% for PET/CT, respectively. The area under the receiver operating characteristics for the MRI and PET/CT were 0.667 and 0.561, respectively ( P = .013). MRI showed significantly higher sensitivity for detecting metastatic lymph nodes than PET/CT ( P = .006). Conclusion MRI was more sensitive than PET/CT for detecting metastatic lymph node in patients with cervical cancer.

A probabilistic atlas of the human brain (Statistical Probabilistic Anatomical Maps: SPAM) was developed by the international consortium for brain mapping (ICBM). It is a good frame for calculating volume of interest (VOI) in many fields of brain images. After calculating the counts in VOI using the product of probability of SPAM images and counts in FDG images, asymmetric indices (AI) were calculated and used for finding epileptogenic zones in mesial temporal lobe epilepsy (mTLE). FDG PET images from 18 surgically confirmed mTLE patients and 22 age-matched controls were spatially normalized to the average brain MRI template of ICBM. Counts from normalized PET images were multiplied with the probability of 12 VOIs from SPAM images in both temporal lobes. Finally AI were calculated on each pair of VOIs, and compared with visual assessment. If AI of mTLE patients were not within 2.9 standard deviation from those of normal control group (P0.008; Bonferroni correction for P0.05), epileptogenic zones were considered to be found successfully. The counts of VOIs in the normal control group were symmetric (AI4.3%, paired t test P0.05) except for those of the inferior temporal gyrus (P0.001). By AIs in six pairs of VOIs, PET in mTLE had deficit on one side (P0.05). Lateralization was correct in only 14/18 of patients by AI, but 17/18 were consistent with visual inspection. In three patients with normal AI, PET images were symmetric on visual inspection. The asymmetric indices obtained by taking the product of the statistical probability anatomical map and FDG PET, correlated well with visual assessment in mTLE patients. SPAM is useful for the quantification of VOIs in functional images.