Potential Protective Role of Cyrtopodion Scabrum in Antioxidant Parameters in Serum and Liver of Rats with 5-FU-Induced Oxidative Damage.

Chemotherapy is the main approach for the treatment of cancer; however, it often causes unpleasant oxidative damages. Therefore, the development of an effective alternative/complementary therapy with improved tumor suppression efficiency and lower adverse effects is highly required. Recently, it has been shown that Cyrtopodion scabrum extract (CsE) is an effective and selective tumor suppressor medicine. The present study investigated the antioxidant activity of Cyrtopodion scabrum homogenate (CsH) and CsE and their effects on attenuating 5-fluorouracil (5-FU)-induced liver dysfunction in rats. A total of 60 male rats (weight: 200-220 g) were divided into six groups and treated for 14 days. The control (group I) and 5-FU (group II) groups received distilled water and 5-FU, respectively. The other four groups were orally administered with CsE, CsH, CsE+5-FU, and CsH+5-FU (groups III to VI), respectively by gavages based on a daily schedule. The 5-FU-induced oxidative damage was evaluated by changes in the weight and food and water intake during the treatment and antioxidant parameters in the liver and serum of the treated rats. The obtained data indicated that the administration of CsH and CsE significantly improved liver function and defense system of antioxidants by attenuating the levels or activities of malondialdehyde, superoxide anion, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase and decrease of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, total antioxidant capacity, glutathione, total protein, and albumin in the liver and serum, induced by 5-FU treatment. The obtained data of the current study suggested that CsH and CsE play a protective role in the imbalance elicited by 5-FU and can be used as alternative/complementary supplements with 5-FU to reduce oxidative damages which is the consequence of reactive oxygen species production in cancerous patients.

Composition and Anti-Toxicity Effects of Cichorium intybus Distillate on Serum Antioxidant Status in Carbon Tetrachloride-Treated Rats.

The role of oxidative stress in female fertility is a compelling area for research. According to traditional medicine, Cichorium intybus, known as Kasni, is believed to improve fertility. For this purpose, the effects of C. intybus distillate (CI) on blood antioxidant status were assessed in rats with carbon tetrachloride (CCl4)-induced toxicity. The rats were assigned to four experimental groups of Control, CI, CCl4, and CI+CCl410 (n=10 in each group). The level of antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT), as well as lipid peroxidation and reduced glutathione (GSH) level, were measured in serum samples. In the second part of the study, the antioxidant activity and phytochemical composition of the hydrodistillate of C. intybus aerial parts were determined by DPPH radical scavenging and gas chromatography-mass spectrometry analysis, respectively. The administration of CCl4 decreased the enzyme activities of GPx, GR, and CAT which were significantly ameliorated after CI administration. The decreased level of serum GSH following CCl4 administration was not considerably elevated in the CI+CCl4 group. Furthermore, the level of malondialdehyde in the serum of CI+CCl4 rats was decreased, compared to the CCl4 group. The main compositions of the essential oil from the C. intybus distillate were the antioxidants of Pulegone (8.10%), Piperitenone (7.68%), dihydroactinidiolide (5.0%), and carvone (4.18%). The antioxidant activity of the distillate was obtained at 75µg/l using the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) test. In general, the results of the present study demonstrated that C. intybus distillate, as a safe herbal remedy, can attenuate CCl4-induced oxidative damages via boosting the endogenous antioxidant defense system.

Use of chicken embryonated eggs for evaluating the virulence of Toxoplasma gondii.

The objective of the present study was to examine the virulence of Toxoplasma gondii RH strain tachyzoites in embryonated eggs after continuous passage in Vero cell line. The first T. gondii tachyzoites was considered low passage (no passage) and then passaged for 80 times on Vero as high passage. Groups of 9-day-old embryonated eggs with ten eggs in each group were inoculated with 102,103 and 104 of low or high-passage T. gondii tachyzoites, and any mortality was recorded. Suitable samples from different tissues (liver, heart, and brain) of the dead embryos were collected for histopathological study. In this study, the mortality in group 103 and 104 was observed, but there was no significant differences in mortality rate in T. gondii low passage and high passage. This finding exactly correspond to previous studies that were performed in mice as animal model for T. gondii RH strain. Thus on base of this study we could introduce the embryonated eggs as an appropriate animal model to evaluate the virulence of T. gondii tachyzoites.

Optimization of murine model for Besnoitia caprae.

It has been shown that mice, particularly the BALB/c ones, are susceptible to infection by some of the apicomplexan parasites. To compare the susceptibility of the inbred BALB/c, outbred BALB/c and C57 BL/6 to Besnoitia caprae inoculation and to determine LD50, 30 male inbred BALB/c, 30 outbred BALB/c and 30 C57 BL/6 mice were assigned into 18 groups of 5 mice. Each group was inoculated intraperitoneally with 12.5 × 10(3), 25 × 10(3), 5 × 10(4), 1 × 10(5), 2 × 10(5) tachyzoites and a control inoculum of DMEM, respectively. The inbred BALB/c was found the most susceptible strain among the experienced mice strains so the LD50 per inbred BALB/c mouse was calculated as 12.5 × 10(3.6) tachyzoites while the LD50 for the outbred BALB/c and C57 BL/6 was 25 × 10(3.4) and 5 × 10(4) tachyzoites per mouse, respectively. To investigate the impact of different routes of inoculation in the most susceptible mice strain, another seventy five male inbred BALB/c mice were inoculated with 2 × 10(5) tachyzoites of B. caprae via various inoculation routes including: subcutaneous, intramuscular, intraperitoneal, infraorbital and oral. All the mice in the oral and infraorbital groups survived for 60 days, whereas the IM group showed quicker death and more severe pathologic lesions, which was then followed by SC and IP groups. Therefore, BALB/c mouse is a proper laboratory model and IM inoculation is an ideal method in besnoitiosis induction and a candidate in treatment, prevention and testing the efficacy of vaccines for besnoitiosis.

Seroprevalence of Neospora caninum infection in free ranging chickens (Gallus domesticus).

Recently chickens are considered as an important intermediate hosts for Neospora caninum. Free range chickens expose to infection with N. caninum oocysts because they feed from the ground therefore they could be a good index of the environmental contamination. We studied N. caninum infection in free range chickens by serological. One hundred and fifty chickens purchased from five regions from Fars province and their blood were used for serological testing. Antibodies to N. caninum were found in 26 (17.33 %) of 150 serum samples by MAT. This study is the first to describe the presence of antibodies to N. caninum in chicken in Iran. These serological results indicate a widespread exposure of free range chickens to N. caninum in south of Iran.

Suspension culture of Besnoitia caprae by murine macrophage.

Besnoitia caprae is a tissue cyst-forming protozoan that infects goats and has considerable economic importance in certain regions of Asia and Africa. Murine macrophage J774 cell line was inoculated with tachyzoites of Besnoitia caprae (BC-Pars isolate) collected from mice. A significant growth of tachyzoites was observed in J774. Mice were inoculated with tachyzoites harvested from J774 cell culture. Skin samples from the mice infected with tachyzoites of BC-Pars were PCR positive. One mouse showed alopecia and skin lesions on 45 DPI. Dermal lesions started from around right eye and gradually developed more and more. After euthanasia on 60 DPI, histopathological evaluation of skins around the eye showed necrosis of the epidermis and follicular adnexa with chronic inflammatory cell infiltration. Histopathological sections of their skin showed the presence of necrosis and mononuclear cell infiltration. To the authors' knowledge, this is the first report of successful production of Besnoitia caprae tachyzoites was achieved in vitro by suspension culture technique. Another interesting finding is the report of the alopecia and skin lesions around the eye in mouse that quite similar to lesions of goats due to infection of Besnoitia caprae.

Experimental Neospora caninum infection in domestic bird's embryonated eggs.

To date, there are no reports regarding comparison between different bird species in Neospora. caninum infection. In the present study 70 embryonated eggs from quail, partridge, broiler and egg laying chickens were divided into 7 groups equally. Six groups in each species were inoculated with different dilutions (10, 10(2), 10(3), 10(4), 10(5), and 10(6)) of tachyzoites/embryonated egg in the chorioallantoic membrane and the seventh group was considered as control. The mortality rates and clinical signs were studied. All the egg laying chickens and some of the broiler chickens and quails showed neurologic signs like. The results revealed that the mortality rate was dose dependent in broiler chicken embryonated eggs. But mortality rate was dose independent in egg laying chickens and quail. Partridge revealed 100 % mortality rate in all doses. The LD50 in broiler chicken embryonated was 10(2.3). In conclusion, LD50 in the broiler chickens is the lowest between different animal models which shows that the broiler chicken embryonated egg is the best animal model for experimental inducing of neosporosis. Partridge is the most susceptible bird to N. caninum infection. These results reinforce that there is genetic susceptibility to N. caninum in chickens like mice and provide new insights to reach an inexpensive and available animal model for N. caninum infection.

First isolation and establishment of in vitro culture of Theileria lestoquardi from a naturally infected cow.

Theileria infected cell line was isolated from the prescapular lymph node of an adult crossbred cow. Molecular study confirmed this cell line of bovine lymphocyte has been transformed by the Theileria lestoquardi. This strain of T. lestoquardi designated Ka-6 and sheep were inoculated with this strain didn't show any clinical signs of theileriosis which shows the significance of this cell line to develop a tissue-culture vaccine against malignant ovine theileriosis. Contrary to accepted belief that the T. lestoquardi not capable of causing disease in cattle, the present study describes the first isolation and establishment of in vitro culture of T. lestoquardi-infected cell line from a naturally infected cow with typical singes of acute theileriosis.

Suspension culture of Neospora caninum by Theileria annulata-infected cell line.

There are some limiting aspects of scaling up the Neospora caninum tachyzoites in continuous cell lines, particularly as related to the absence of surface attachment. In this study, suspension cell culture of Theileria annulata-infected lymphoblastoid (TIL) was used as a host cell for the continous production of N. caninum tachyzoites. The numbers of free tachyzoites in the medium supernatant were showed regularly increased up to the day 6 post-cultivation. Transmission electron microscopy demonstrated that N. caninum tachyzoites invaded the TIL cells and multiplied intracellularly. This showed that the tachyzoites were successfully proliferated in TIL cells and were released in complete Dulbecco's modified Eagle's medium. This is a successful report of in vitro cultivation of N. caninum tachyzoites achieved by using suspension host cell culture.

Evaluation of Cross Immunity and Histopathological Findings in Experimentally Infected BALB/c Mice with Neospora caninum and Besnoitia caprae.

BACKGROUND: Caprine besnoitiosis is an economically important disease of goats. Neospora caninum, another coccidian parasite of worldwide distribution, infects several animal species and is a major cause of abortion in cattle. Combined infections of N. caninum and Besnoitia caprae can occur in geographical areas endemic for both species of parasite in goats. This experiment was conducted to investigate the possible cross-immunity between these two infections in experimentally infected BALB/c mice. METHODS: Forty BALB/c mice were divided into four equal groups. The mice of Groups 1 and 4 were inoculated with 1×10(6) live virulent tachyzoites of N. caninum (NC-1), while animals of Groups 2 and 3 were inoculated with sterile tissue culture medium. Each mouse in Groups 1 and 2 was challenged 28 days later with 1×10(6) live virulent bradyzoites of B. Caprae (BC-1). RESULTS: Following the challenge, the mice in Groups 1 and 2 showed 100% morbidity and 100% mortality within 9 days post infection, while all the animals of Groups 3 and 4 remained alive. The dead animals were necropsied. The survivors (mice in Group 3 and 4) were euthanized 9 days after inoculation and the gross and histopathological lesions in different organs were investigated. CONCLUSION: Immunization and challenge experiments with lethal dose of B. caprae in the highly susceptible BALB/c mice showed no cross-protection between N. caninum and B. caprae.

Probiotic inhibits the cytopathic effect induced by Escherichia coli O157:H7 in Vero cell line model.

AIMS: The effectiveness of four strains of Bifidobacteria against enterohemorrhagic Escherichia coli O157:H7 infection was studied using a Vero cell model. METHODS AND RESULTS: E. coli O157 was inoculated on the Vero cell line before and after treatment with probiotic. The cytopathic effect (CPE) was evaluated during 24 h of incubation. The results indicated that Shiga toxin activity was inhibited by the probiotic. To prevent a Stx2 CPE, the probiotic needs one log more than the Stx1. CONCLUSION: The Vero cell assay, in particular, is a good model to evaluate the effect of Bifidobacteria inhibiting bacterial attachment because of soluble substances and the competitive aspect and could be used in a variety of foods like milk and yoghurt to protect pathogen bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Probiotics could control pathogenic bacteria and Vero cell introduce as a model for evaluation of probiotics against pathogen bacteria.

Seroprevalence of Neospora spp. in horses in South of Iran.

Neospora caninum, an apicomplexan protozoan parasite, is recognized as a major cause of abortion in cattle. However, limited information is presently available on the seroprevalence of Neospora antibodies in horses worldwide. The aim of the present study is to determine serological prevalence of Neospora infection in horses in Iran. Blood samples were obtained from 200 horses and tested for serum antibodies against Neospora spp. by the Neospora modified direct agglutination test (N-MAT). Antibodies were found in 64 (32%) horses being tested with titers of 1:80. This is the first serological survey for Neospora antibodies performed on horses in Iran.

Seroprevalence of Neospora spp. in horses in South of Iran

Neospora caninum, an apicomplexan protozoan parasite, is recognized as a major cause of abortion in cattle. However, limited information is presently available on the seroprevalence of Neospora antibodies in horses worldwide. The aim of the present study is to determine serological prevalence of Neospora infection in horses in Iran. Blood samples were obtained from 200 horses and tested for serum antibodies against Neospora spp. by the Neospora modified direct agglutination test (N-MAT). Antibodies were found in 64 (32%) horses being tested with titers of 1:80. This is the first serological survey for Neospora antibodies performed on horses in Iran.

Contamination of sheep carcasses with verocytotoxin producing Escherchia coli during slaughtering.

Verocytotoxin producing Escherchia coli (VTEC) infection has been associated with diarrhoea. Sheep, like other ruminants, appear to have VTEC in their feces and are regarded as natural reservoirs of these pathogens. As contaminated sheep products can serve as a risk factor, their role as a food safety threat should be considered. The carcasses of sheep during slaughtering were examined for the presence of VTEC, which were isolated from 19 (9.5%) of 200 animals. Most of the 19 VTEC isolates (73.68%) contained Shiga toxin 1 and 2 genes. Eight (4%) carcasses of sheep were contaminated by E. coli O157:H7. The monthly prevalence of VTEC in sheep was obtained and ranged from 0.2% to 9.5% and was at its highest level in spring and late summer, which is in parallel to the seasonal variation in reported cases of O157 VTEC infections in humans. This study showed that VTEC are widely distributed in southern Iranian sheep.

Experimental infection of embryonated eggs of chicken with Besnoitia caprae.

Knowledge on parasites of the genus Besnoitia, especially Besnoitia caprae, is sparse. Besnoitia caprae, an obligate intracellular protozoan parasite belonging to the phylum Apicomplexa, is the causative agent of caprine besnoitiosis. This experiment was conducted to determine the infectivity of the bradyzoites and the resultant histopathological lesions after inoculation of B. caprae bradyzoites in the embryonated egg. Eight groups, each having six embryonated eggs, were assigned in this experiment. Seven groups were inoculated with different doses of B. caprae bradyzoite inoculums (1x10(3), 1x10(4), 1x10(5), 1x10(6), 5x10(6), 1x10(7) and 2x10(7)) via the allantoic cavity route. The 8th group was considered as control. The embryos inoculated with higher doses showed mortality between 14 and 21 days of incubation (5-12 days post-infection). Those embryos that received lower doses were hatched on day 21 of incubation; however, they presented loss of feathers and paralysis and showed hyperemia in the skin of the feet regions. Histopathological sections of the skin revealed the presence of hemorrhages, hyperemia and inflammatory responses. Some of the chickens were euthanized after 50 days postinfection (DPI) and histopathological examination of their tissues revealed haemorrhages and coagulative necrosis with the presence of mononuclear cells infiltration in the liver and heart with interstitial pneumonia. It seems that the embryonated eggs could be a useful model to study the parasite's biology.

Blood-brain barrier and neuronal membrane transport of 6-[18F]fluoro-L-DOPA.

The transport of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) across the blood-brain barrier (BBB) and neuronal membranes was compared with that of L-3,4-dihydroxyphenylalanine (L-DOPA) in rats. The carotid injection method was used as a direct measurement of [18F]FDOPA, 1-[14C]-L-DOPA, and 3-[14C]-L-DOPA transport across the BBB, while isolated nerve terminals were used to examine neuronal membrane transport of [3H]-L-DOPA. [18F]FDOPA appeared to use the same large neutral amino acid carrier for BBB transport as L-DOPA and L-phenylalanine. In addition, carbidopa [L-alpha-hydrazino-alpha-methyl-beta-(3,4-dihydroxyphenyl)propionic acid] was found not to have direct interference with the transport carrier on the BBB, but indirectly inhibited aromatic L-amino acid decarboxylase (AAAD) activity in brain endothelium by depletion of pyridoxal phosphate, a necessary cofactor of the enzyme. In striatal and cortical synaptosomes, [3H]-L-DOPA uptake was inhibited by non-radioactive L-DOPA, FDOPA, and 6-fluoro-L-meta-tyrosine (6-FMT). The inhibition was significantly greater in terminals isolated from the striatum than in those from the cerebral cortex. FDOPA, 6-FMT, and L-DOPA equally inhibited the neuronal transport of [3H]-L-DOPA. This suggests that FDOPA and 6-FMT compete with L-DOPA at similar transport sites at the neuronal membrane.

Quantitative imaging of gene induction in living animals.

Methods to repeatedly, non-invasively, and quantitatively image gene expression in living animals are rapidly emerging and should fundamentally change studies of gene expression in vivo. We previously developed assays utilizing positron emission tomography (PET) to image reporter gene expression. In this paper we: (1) describe a new bi-directional, tetracycline-inducible system that can be used to pharmacologically induce target gene expression and to quantitatively image induced expression by using a PET reporter gene; (2) demonstrate the potential of this system in transient and stable cell transfection assays; and (3) demonstrate the ability to repetitively and quantitatively image tetracycline and tetracycline analog induction of gene expression in living animals. We utilize the dopamine type-2 receptor (D(2)R) and the mutant herpes-simplex virus type 1 thymidine kinase (HSV1-sr39tk) reporter genes to validate this system. We utilize microPET technology to show that quantitative tomographic imaging of gene induction is possible. We find a high correlation (r(2) = 0.98) between 'target' and reporter gene expression. This work establishes a new technique for imaging time-dependent variation of gene expression both from vectors with inducible promoters and in transgenic animals in which pharmacologic induction of gene expression must be monitored. These techniques may be applied both in gene therapy and for the study of gene expression in transgenic animals.

Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression.

UNLABELLED: 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) has been used as a reporter probe to image expression of herpes simplex virus type-1 thymidine kinase (HSV1-tk) reporter gene in living animals. Our aim was to study the kinetics, biodistribution, stability, dosimetry, and safety of [(18)F]FHBG in healthy human volunteers, preparatory to imaging patients undergoing HSV1-tk gene therapy. METHODS: [(18)F]FHBG was synthesized with a specific activity of 37,000--444,000 GBq/mmol and a radiochemical purity > 99%. Ten healthy volunteers consented to participate in the study. A transmission scan was obtained before bolus injection of 70.3--229.4 MBq [(18)F]FHBG into a hand vein, followed by dynamic PET imaging with 4 consecutive emission scans. Warmed hand-vein blood was withdrawn at various times after injection for blood time--activity measurements. Electrocardiography, blood pressure, and blood and urine pharmacologic parameters were measured before and after injection of the [(18)F]FHBG tracer (n = 5). The stability of [(18)F]FHBG in the urine was analyzed. Attenuation-corrected images were reconstructed using the ordered-subsets expectation maximization algorithm. Image region-of-interest time-activity data were used with the MIRD program to estimate absorbed radiation dosages. RESULTS: [(18)F]FHBG had rapid blood clearance; only 8.42% +/- 4.76% (mean +/- SD) of the peak blood activity remained at approximately 30 min. The average ratio of plasma activity to whole-blood activity during the study was 0.91 +/- 0.04. Penetration of [(18)F]FHBG across the blood-brain barrier was not observed. The primary routes of clearance were renal and hepatobiliary. High activities were observed in the bladder, gut, liver, and kidneys, but <0.0002% of the injected dose per gram was observed in other tissues. In the urine, 83% of activity 180 min after injection was stable [(18)F]FHBG. Blood and urine pharmacologic parameters did not change significantly after injection of the [(18)F]FHBG tracer. The bladder absorbed the highest radiation dose. CONCLUSION: [(18)F]FHBG has the desirable in vivo characteristics of stability, rapid blood clearance, low background signal, biosafety, and acceptable radiation dosimetry in humans. This study forms the foundation for using [(18)F]FHBG in applications to monitor HSV1-tk reporter gene expression.

Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors.

Biodistribution, magnitude and duration of a therapeutic transgene's expression may be assessed by linking it to the expression of a positron emission tomography (PET) reporter gene (PRG) and then imaging the PRG's expression by a PET reporter probe (PRP) in living animals. We validate the simple approach of co-administering two distinct but otherwise identical adenoviruses, one expressing a therapeutic transgene and the other expressing the PRG, to track the therapeutic gene's expression. Two PET reporter genes, a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) and dopamine-2 receptor (D(2)R), each regulated by the same cytomegalovirus (CMV) promoter, have been inserted into separate adenoviral vectors (Ad). We demonstrate that cells co-infected with equivalent titers of Ad-CMV-HSV1-sr39tk and Ad-CMV-D(2)R express both reporter genes with good correlation (r(2) = 0.93). Similarly, a high correlation (r(2) = 0.97) was observed between the expression of both PRGs in the livers of mice co-infected via tail-vein injection with equivalent titers of these two adenoviruses. Finally, microPET imaging of HSV1-sr39tk and D(2)R expression with 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl) guanine ([(18)F]FHBG) and 3-(2-[(18)F]fluoroethyl)spiperone ([(18)F]FESP), utilizing several adenovirus-mediated delivery routes, illustrates the feasibility of evaluating relative levels of transgene expression in living animals, using this approach.

8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET.

UNLABELLED: We have synthesized and evaluated 8-[18F]fluoropenciclovir (FPCV) and compared it with 8-[18F]fluoroganciclovir (FGCV) for monitoring the expression of herpes simplex virus type 1 thymidine kinase (HSV1 -tk) reporter gene in cell culture and in vivo. METHODS: C6 rat glioma cells stably transfected with HSV1-tk (C6-stb-tk+) and control C6 cells were evaluated for their ability to accumulate FGCV versus FPCV. For in vivo studies, 15 mice were injected by tail vein with increasing levels of an adenoviral vector carrying HSV1-tk. Forty-eight hours later the mice were injected with FPCV and killed 3 h later. The percentage injected dose per gram (%ID/g) liver was then determined. Two additional mice were studied by microPET and autoradiography using FPCV to image adenoviral-mediated hepatic HSV1-tk reporter gene expression. A tumor-bearing mouse (C6 control and C6-stb-tk+) was imaged with FDG, FGCV, and FPCV. Two mice carrying tumors expressing two different reporter genes, HSV1-tk and dopamine type 2 receptor (D2R), were also imaged by microPET using FPCV (day 1) and 3-(2'-[18F]fluoroethyl)spiperone (FESP) (day 2). RESULTS: FPCV shows a significantly greater accumulation in C6-stb-tk+ cells than does FGCV (P < 0.05). Over identical ranges of adenoviral administration, mouse liver shows a higher %ID/g liver for FPCV (0%-9%) compared with our previously reported results with FGCV (0%-3%). In C6 control and C6-stb-tk+ tumor-bearing mice, FPCV has a greater accumulation than does FGCV for equal levels of HSV1-tk gene expression. In mice carrying tumors expressing either HSV1-tk or D2R reporter genes, there is a corresponding retention of FPCV and FESP, respectively. CONCLUSION: These results indicate that FPCV is a better reporter probe than is FGCV for imaging lower levels of HSV1 -tk gene expression in vivo. The results also reveal the ability to monitor the expression of two distinct reporter genes in the same animal using reporter probes specific for each gene.