scholarly journals In vitro and in vivo studies of cytotoxic effects of FeSO4 nanoparticles

2021 ◽  
Vol 23 (1) ◽  
pp. 1-6
Author(s):  
Elahe Moeini ◽  
Mojtaba Bonyadian ◽  
Hadi Ebrahimnejad ◽  
Iraj Karimi ◽  
Nahid Askari
Keyword(s):  
Electron Microscopy ◽  
Adverse Effects ◽  
Annexin V ◽  
In Vivo Studies ◽  
Iron Particles ◽  
Chi Square ◽  
Flow Cytometric Study ◽  
Ht 29

Background and aims: Using iron as a food additive usually causes undesirable sensory changes and side effects in humans. In this study, we made iron (Fe) nanoparticles (NPs) and studied the cytotoxicity of FeSO4 bulk and NPs on HT-29 cells and different doses of these particles on rat intestine. Methods: Particle size of nanoscale was achieved by mechanical technique. Iron particles were characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The effect of iron particles with different concentrations (6.25, 3.125, and 1.57 mM/mL) on the colon cell line was performed using the MTT assay at 24, 48, and 72 hours. Apoptosis and necrosis of the cells were assessed using Annexin V-FITC staining and propidium iodide (PI) at 24 h. In an in vivo study, Taftoon bread was produced from fortified wheat flour with FeSO4 bulk and NPs, which are recommended in human diet (9, 18, and 27 mg of elemental iron/kg flour). Wistar rats were fed daily with fortified bread for 21 days and their colon and small intestine were then evaluated histopathologically. Statistical analyses were performed using SPSS 22.0 software by chi-square test. Results: The synthesized FeSO4 NPs were smaller than 100 nm, and they had more adverse effects on the viability of the HT-29 cells compared to the bulk- FeSO4 at 72 hours. Flow cytometric study showed that the early apoptosis of cells by the bulk form was more than the NPs, but at the low concentration (1.57 mM/mL), the NPs induced more necrosis than the bulk particles (P=0.063). The survival rate of cells facing all concentrations of NPs and bulk- FeSO4 decreased dose dependently (P=0.075). In vivo results revealed that there were no pathological changes in rats’ intestinal tissues. Conclusion: The bulk and NPs of iron have adverse effects on the HT-29 cells, but no histopathological changes were seen on rats’ intestinal cells.

Derivatives of Deoxypodophyllotoxin Induce Apoptosis Through Bcl-2/Bax Proteins Expression

2020 ◽  
Vol 20 ◽  
Author(s):  
Ya-Nan Li ◽  
Ni Ning ◽  
Lei Song ◽  
Yun Geng ◽  
Jun-Ting Fan ◽  
...  
Keyword(s):  
Annexin V ◽  
Mtt Method ◽  
Anthriscus Sylvestris ◽  
Anti Tumor Activity ◽  
Derivatives Of ◽  
Toxicity In Vitro ◽  
Ht 29 ◽  
Mcf 7

Background: Deoxypodophyllotoxin, isolated from theTraditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant antitumor activity with strong toxicity in vitro and in vivo. Objective: In this article, we synthesized a series of deoxypodophyllotoxin derivatives, and evaluated their antitumor effectiveness.Methods:The anti tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. Results: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29 andMG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. Conclusion: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

scholarly journals AN ANALYSIS OF COLLAGEN SECRETION BY ESTABLISHED MOUSE FIBROBLAST LINES

1964 ◽  
Vol 22 (1) ◽  
pp. 227-258 ◽  
Author(s):  
Burton Goldberg ◽  
Howard Green
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Mouse Fibroblast ◽  
In Vivo Studies ◽  
In Vitro Synthesis ◽  
Collagen Secretion ◽  
Golgi System ◽  
Alternative Theories

In vitro synthesis of collagen by established mouse fibroblast lines has been examined by electron microscopy. During rapid growth (log phase), when collagen could not be detected in the cultures, the cells lacked a well developed granular ergastoplasm and Golgi system. Upon cessation of growth (stationary phase), collagen accumulated in the cultures and the cells demonstrated highly developed granular and smooth ergastoplasm. Collagen appeared to be synthesized in the rough-surfaced endoplasmic reticulum and to be transported as a soluble protein to the cell surface by vesicular elements of the agranular ergastoplasm. Fusion of the limiting membranes of these vesicles with the cell membrane permitted the discharge of the soluble collagen into the extracellular space, where fibrils of two diameter distributions formed. The secretion of collagen is concluded to be of the merocrine type. Alternative theories of collagen secretion are discussed and the data for established lines compared with the results of other in vitro and in vivo studies of collagen fibrillogenesis.

BIX-01294-enhanced chemosensitivity in nasopharyngeal carcinoma depends on autophagy-induced pyroptosis

2020 ◽  
Vol 52 (10) ◽  
pp. 1131-1139
Author(s):  
Qian Li ◽  
Min Wang ◽  
Yan Zhang ◽  
Liuqian Wang ◽  
Wei Yu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Caspase 3 ◽  
Southern China ◽  
Annexin V ◽  
In Vivo Studies ◽  
Cell Swelling ◽  
Chemotherapeutic Drugs ◽  
Double Positive

Abstract Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Southeast Asia. Nowadays, radiotherapy is the therapy of choice for NPC patients, and chemotherapy has been found as an alternative treatment for advanced NPC patients. However, finding novel drugs and pharmacologically therapeutic targets for NPC patients is still urgent and beneficial. Our study showed that BIX-01294 (BIX) can induce autophagic vacuoles formation and conversion of LC3B-I to LC3B-II in NPC cells in both dose- and time-dependent manners. Notably, the combination of BIX and chemotherapeutic drugs significantly decreased the cell viability and increased the lactate dehydrogenase release. Meanwhile, BIX plus cis-platinum (Cis) treatment induced pyroptosis in NPC cells as featured by cell swelling and bubble blowing from the plasma membrane, the increased frequency of annexin V and propidium iodide (PI) double-positive cells, as well as the cleavage of gasdermin E (GSDME) and caspase-3. Moreover, the deficiency of GSDME completely shifted pyroptosis to apoptosis. Furthermore, the inhibition of autophagy by chloroquine and the knockout of ATG5 gene significantly blocked the BIX-induced autophagy as well as pyroptosis in both in vitro and in vivo studies. Our data demonstrated that BIX-combined chemotherapeutic drugs could induce the Bax/caspase-3/GSDME-mediated pyroptosis through the activation of autophagy to enhance the chemosensitivity in NPC.

scholarly journals Mitochondrial damage: a possible mechanism of the “topical” phase of NSAID induced injury to the rat intestine

Gut ◽  
1997 ◽  
Vol 41 (3) ◽  
pp. 344-353 ◽  
Author(s):  
S Somasundaram ◽  
S Rafi ◽  
J Hayllar ◽  
G Sigthorsson ◽  
M Jacob ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Small Intestine ◽  
Electron Transport ◽  
Oxidative Phosphorylation ◽  
In Vivo Studies ◽  
Tolerability Profile ◽  
Marker Enzyme ◽  
Subcellular Organelle

Background—The “topical” effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage.Aim—To examine the possible mechanism of the “topical” phase of damage in the small intestine.Methods—Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode.Results—The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the “topical” phase of NSAID induced damage.Conclusion—Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the “topical” phase of damage induction.

scholarly journals EPR Oximetry Sensor—Developing a TAM Derivative for In Vivo Studies

2017 ◽  
Vol 76 (1-2) ◽  
pp. 19-28 ◽  
Author(s):  
Agnieszka Boś-Liedke ◽  
Magdalena Walawender ◽  
Anna Woźniak ◽  
Dorota Flak ◽  
Jacek Gapiński ◽  
...  
Keyword(s):  
Tumor Therapy ◽  
Mri Contrast Agents ◽  
Response To Treatment ◽  
In Vivo Studies ◽  
Spectral Studies ◽  
Special Importance ◽  
Liquid Environment ◽  
Ht 29

Abstract Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.

scholarly journals In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads

2018 ◽  
Vol 9 (1) ◽  
pp. 190-199 ◽  
Author(s):  
Geet P. Asnani ◽  
Chandrakant R. Kokare
Keyword(s):  
Colon Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Colon Cancer Cell Line ◽  
Colon Cancer Cell ◽  
In Vivo Studies ◽  
Ht 29

AbstractThe aim of this study was to formulate a novel dual crosslinked hydrogel bead using Portulaca mucilage for colon-targeted delivery of 5-fluorouracil (5-FU) and evaluate its safety, specificity and efficacy. The ionotropic gelation technique was employed to prepare the hydrogel beads of Portulaca mucilage. For this, the mucilage was initially crosslinked with alginate and calcium ions. Epichlorohydrin was employed as a crosslinker in the second crosslinking step. The formulation was subjected to in vitro and in vivo studies to evaluate morphology, size, cytotoxicity, and organ distribution. Human HT-29 colon cancer cell-line was used for in vitro assays and in vivo studies were performed in Wistar rats to assess the usefulness and effectiveness of the formulation for colon cancer therapy. Microsphere sizes ranged from 930 to 977μm and possessed a high level of drug encapsulation efficiency (ca. 78% w/w). Compared with 5-FU solution (Tmax = 1.2 h, mean resident time: MRT = 3.3h) the dual crosslinked Portulaca microspheres exhibited sustained drug release after oral administration to rats (Tmax = 16h, MRT = 14h). The relative bioavailability of 5-FU solution and the microspheres were 100 and 93.6% respectively. Tissue distribution studies indicated high concentration of 5-FU in colon. In-vitro anticancer assay demonstrated IC50 value of 11.50 μg/ml against HT-29 colon cancer cell line. The epichlorohydrin cross-linked Portulaca microspheres prepared in this study provided sustained release of 5-FU up to 16h in the colonic region and enhanced the antitumor activity of the neoplastic drug. The formulation is hence an ideal carrier system for colon-targeted drug delivery.

The SET Oncogene, a Potent PP2A Inhibitor, Is Elevated in CLL and Antagonism of SET Induces Apoptosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 802-802
Author(s):  
Dale J. Christensen ◽  
Karen M. Bond ◽  
Alicia D. Volkheimer ◽  
Jessica Oddo ◽  
Youwei Chen ◽  
...  
Keyword(s):  
B Cells ◽  
Western Blotting ◽  
Colorimetric Assay ◽  
Annexin V ◽  
In Vivo Studies ◽  
Community Control ◽  
Pp2a Activity ◽  
Mimetic Peptides

Abstract Abstract 802 Background and Significance: Even though we have treatments for CLL, it remains an incurable leukemia. We need new and better treatments for this disease. The Akt kinase is usually constitutively activated (phosphorylated) in CLL, and it acts to maintain CLL cell viability. The tumor suppressor protein phosphatase 2A is important in deactivation of Akt, the mitogen activated protein kinases (MAPK) p38, JNK, ERK, and NFkB (through IkK). We developed apoE-mimetic peptides that potently decrease phosphorylation of Akt and MAPKs, decrease TNF and nitric oxide synthase expression, and display anti-inflammatory activity in vitro and in vivo by antagonism of SET, a potent physiological inhibitor of PP2A. Others have reported that PP2A activity is reduced and that SET is overexpressed in cells of chronic myelocytic leukemia patients. Increased SET expression with consequent decreased PP2A activity leads to dysregulated kinase signaling. We show here that SET is also overexpressed in CLL cells, and that SET antagonist apoE-mimetic peptides kill CLL cells. Methods: Patients were from the Duke University and V.A. Medical Centers, and normal controls were from the community. Control normal PBMC were isolated by ficoll-Hypaque centrifugation, and CD19+ CLL or normal B cells were purified using negative selection with antibodies. We determined cytotoxicity using the MTS colorimetric assay. ApoE-mimetic peptides were prepared by chemical synthesis. Western blotting was used with anti-SET and anti-beta-actin antibodies. Apoptosis assays were performed with the annexin-V:propidium iodide staining method. Results: Samples from 17 CLL patients and 5 normal volunteers were examined by Western blotting. SET protein levels were 6.2-fold higher in CLL cells than in normal B cells. The apoE-mimetic COG compounds are peptides of 17 to 34 amino acids derived from the ligand-binding region of the apolipoprotein E holoprotein, and they act by binding to SET and preventing the inhibition of PP2A. This results in a net increase in PP2A activity in CLL cells. We have examined 11 COG peptides. Each of the 11 peptides displayed some cytotoxicity for CLL cells in vitro, irrespective of the patients' stages and other good or bad prognostic findings. 12 of 17 CLL patients were Rai stage 0 at presentation, and 5 were stage 1 or 2. They had been followed 4.2 yr (median; range 1.0 – 24.1 yr). 2 of 16 were CD38 positive, and 6 of 15 were Zap-70 positive. Of 15 analyzed, 6 had unmutated IgVH gene. 11 of 17 patients had not been treated. Peptide COG449 was the most potent, while a control peptide with an inverted apoE sequence had no activity. COG449 induced cell death in a dose-dependent fashion in all patients' samples, with a mean ED50 of 80 nM. The ED50 of COG449 for normal B cells was very high (> 10,000 nM). Annexin-V staining indicated that apoptosis was induced at concentrations in good agreement with the ED50 for cytotoxicity of the compounds tested. In vivo studies in normal mice using COG449 show no toxicity even at doses of 100 mg/kg when delivered by subcutaneous injection. Conclusions: We demonstrated SET overexpression in CLL cells and that apoE-mimetic peptides bind SET to de-inhibit PP2A. This results in apoptosis and death of CLL cells in vitro with high efficacy and potency (low nanomolar ED50s). CLL cells are killed preferentially compared to normal PBMC and B cells. Preliminary studies show that the peptide is nontoxic in normal mice. Trials in CLL patients will help determine the efficacy in vivo. Disclosures: Christensen: Cognosci Inc.: Employment. Oddo:Cognosci Inc.: Employment. Vitek:Cognosci Inc.: Employment, Equity Ownership.

560 Alpha-tocopheryloxyacetic acid induces apoptosis of murine rhabdomyosarcoma in vitro while modulating innate and adaptive immune responses in vivo

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A594-A594
Author(s):  
Fernanda Szewc ◽  
Longzhen Song ◽  
Sean Rinella ◽  
Christopher Dubay ◽  
Emmanuel Akporiaye ◽  
...  
Keyword(s):  
Gene Expression ◽  
Flow Cytometry ◽  
T Cells ◽  
Tumor Growth ◽  
Live Cell Imaging ◽  
Control Diet ◽  
Annexin V ◽  
In Vivo Studies

BackgroundRelapsed pediatric sarcomas have a poor prognosis with no available curative options. Alpha-Tocopheryloxyacetic acid (a-TEA) is a redox-silent analog of alpha-tocopherol that induces apoptotic and immunogenic cell death of tumor cells at doses that are not harmful to healthy normal cells. In a first-in-human clinical trial, a-TEA was well tolerated in adults with advanced solid tumors (NCT02192346), but has not yet been studied in pediatric sarcoma. We used a murine model of rhabdomyosarcoma (M3-9-M RMS) to assess the in vitro and in vivo anti-tumor effects of a-TEA.MethodsIn vitro studies were performed on the M3-9-M RMS cell line to measure a-TEA-mediated apoptosis using flow cytometry (Annexin V+/7AAD+ cells) and live cell imaging (Annexin V+ cells). In vivo studies involved orthotopic implantation of luciferase+ M3-9-M tumor cells into syngeneic C57BL/6 recipients. Once tumors were palpable, mice were randomized to a control diet or a-TEA-supplemented chow for 21 days and evaluated for bioluminescence, tumor growth and overall survival. Gene expression of tumor-infiltrating and splenic T cells were analyzed by bulk RNA-Seq and flow cytometry respectively.ResultsM3-9-M RMS treatment with 2.5–100 uM a-TEA induced apoptosis in a dose-dependent manner within 24 hours (p < 0.05) as measured by flow cytometry and live cell imaging. In-vivo studies with the M3-9-M RMS mouse model showed that recipients of a-TEA chow had 30–40% reduced tumor growth (p<0.01) and bioluminescence (p<0.05), leading to prolonged survival (> 4 weeks) compared to recipients of matched control chow (p<0.05). Spleen cells isolated from a-TEA-fed tumor-bearing mice demonstrated increased levels of IFN??+ cells, CD4+ T-cells, Ki-67 proliferation, and decrease in splenic CD11b+ arginase-1+ (p<0.01) and PD-L1+ cells (p<0.05) compared to their counterparts on the control diet. Gene set enrichment analyses of excised RMS tumors after a-TEA treatment revealed increased gene expression of CD24, EP300, CXCR4, and c-Jun as compared to tumors from mice fed control chow.ConclusionsThese data indicate that a-TEA mediates apoptosis of RMS in vitro and suppresses in vivo tumor growth, leading to prolonged survival likely via enhanced activation of adaptive immunity through CD4+ T cells and suppression of innate immunity through regulation of myeloid cell subsets. Furthermore, a-TEA may have direct effects on tumor cell proliferation through EP300 and c-Jun as well as indirect effects on tumor growth by regulation of immune cell recruitment through CD24 and CXCR4 gene expression. Administration of a-TEA as a potential salvage treatment for RMS is warranted.AcknowledgementsThe study was supported by NIH TL1 TR002375 (FS), St. Baldrick’s Stand up to Cancer (SU2C) Pediatric Dream Team Translational Research Grant SU2C-AACR-DT-27-17, NIH/NCI R01 CA215461, American Cancer Society Research Scholar Grant RSG- 18-104-01-LIB, and the Midwest Athletes Against Childhood Cancer (MACC) Fund (CMC). SU2C is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. The contents of this article do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.Ethics ApprovalThe University of Wisconsin-Madison Animal Care and Use Committee approved all protocols (M005915).

scholarly journals ORAL DELIVERY OF SILVER NANOPARTICLES – A REVIEW

2021 ◽  
pp. 9-14
Author(s):  
VEDAMURTHY JOSHI ◽  
FIRDOS SULTHANA ◽  
DINESHA RAMADAS
Keyword(s):  
Silver Nanoparticles ◽  
Gastrointestinal Tract ◽  
Adverse Effects ◽  
Drug Absorption ◽  
Oral Delivery ◽  
English Language ◽  
In Vivo Studies ◽  
Recent Trends

Silver nanoparticles (NP) offer many applications in the science and technology. Oral delivery of such tiny particles results in enhanced drug absorption, reduction in dose, and minimize adverse effects. This review focuses on the mainly on the effects in the gastrointestinal tract along with its in vitro and in vivo studies carried on the silver NP. In this review, we compiled some of the extensive research in the field of silver NP, highlighting some of the most recent trends in the area. Search was carried in English language using Science direct, PubMed, and Google scholar search engines. The effects of silver NP on gastrointestinal tract such as absorption, distribution, metabolism, and elimination were compiled in this review. In addition, selected in vitro and in vivo studies related to the same are discussed. The accumulation of silver NP leading to Arginia condition also emphasized in the study. Silver NP and herbal silver NP in oral delivery can be exploited for the further safer and effective treatment.

scholarly journals Evaluation of 2′-Deoxy-2′-Flouro-5-Methyl-1-β-d-Arabinofuranosyluracil as a Potential Gene Imaging Agent for HSV-tk Expression In Vivo

2002 ◽  
Vol 1 (2) ◽  
pp. 153535002002021
Author(s):  
Mian M. Alauddin ◽  
Atranik Shahinian ◽  
Erlinda M. Gordon ◽  
Peter S. Conti
Keyword(s):  
Emission Tomography ◽  
In Vivo Studies ◽  
In Vitro Experiments ◽  
Tumor Uptake ◽  
Wild Type ◽  
Positron Emission ◽  
Additional Tumor ◽  
Ht 29

2′-Deoxy-2′-flouro-5-methyl-1-β-d-arabinofuranosyluracil (FMAU) has been evaluated in HT-29 cells as a potential positron emission tomography (PET) radiotracer for imaging HSV-tk gene expression in vivo. In vitro experiments demonstrate that the accumulation of [14C]-FMAU in HSV-tk-expressing cells is 2.4-fold ( p < .02), 4.0-fold ( p < .001), and 5.3-fold ( p < .001) higher than the wild-type cells at 1, 3, and 5 hr, respectively. In vivo studies revealed that the tumor uptake in HSV-tk-expressing cells was 2.3-fold ( p < .001), 3.0-fold ( p < .001), and 5.5-fold ( p < .001) higher than the control cells at 1, 2, and 5 hr, respectively. FMAU was found to be more sensitive compared to our earlier studies using 9-[(3-18F-fluoro-1-hydroxy-2-propoxy)methyl]-guanine ([18F]-FHPG) and 9-(4-[18F]-fluoro-3-hydroxy-methylbutyl)guanine ([18F]-FHBG) in the same cell lines, although, the specificity was less than FHBG. These results suggest that while FMAU labeled with PET isotopes may be useful for imaging HSV-tk-expressing tumors in vivo, multitracer studies across additional tumor models are necessary in order to identify an optimal PET radiotracer.

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