Injection Of 131I Research Articles

Investigation of the effect of 131I on blood parameters for thyroid cancer treatment

Hematopoiesis plays a significant role in mammals' life. Hematopoietic damage due to radiations of different arrays, such as ionizing and non-ionizing radiations, could lead to external infections, internal infections, and anemia. Different cancers' treatment using radioactive sources affects the blood parameters (i.e., mature cells, immature cells, and stem cells). In the present paper, the effect of intravascular injection of Iodine-131 (131I) on the blood parameters for thyroid cancer treatment has been investigated utilizing the MCNPX code and Runge-Kutta fourth-order method. The simulation results showed that the accumulated absorbed dose in adult phantom (ORNL whole body phantom) due to normalized intravascular injection of 1 mCi (mCi) of 131I was 1.97 × 10−2 Sv. Based on the accumulated absorbed dose, the blood parameters show a function of injected 131I activity, and their variation in the activity range of 15–300 mCi was calculated using the fourth-order Runge-Kutta method. It shows that injecting 131I with an activity of less than 150 mCi does not have much effect on blood parameters in the period of two to eight days. But, the injection of 131I with an activity greater than 150 mCi and up to a maximum value of 300 mCi, reduces blood parameters by a maximum of 21.21% in a period of two to eight days. Based on the smaller variation (in percent) of blood parameters due to the injection of low activity 131I (<150 mCi), it can be mentioned that thyroid cancer treatment has an insignificant effect on the blood parameters. Besides, it is recommended to integrate the MCNPX code and Runge-Kutta fourth-order method to study the effect of radiation exposure on the blood parameters.

Bone marrow mesenchymal stem cell-mediated ultrasmall gold nanoclusters and hNIS gene synergize radiotherapy for breast cancer.

The human sodium iodide symporter (hNIS) can be linked to the downstream of radiation-sensitive early growth response protein1 (Egr1) promoter, and activated by the Egr1 following 131I treatment. However, the rapid outflow of 131I restricted the radiotherapy effect. To overcome this barrier, ultrasmall gold nanoclusters (usAuNCs) were used to enhance the radiotherapy efficacy of Egr1-hNIS for its radiation sensitization. In this work, we prepared "cell bomb" BMSCs carrying both GSH@AuNCs and Egr1-hNIS. We found that the "cell bomb" can target TNBC tumor and reach a maximum 131I concentration 9 h following 131I injection. Colony formation assay revealed that 131I, 131I combined with GSH@AuNCs could independently inhibit 39.5% and 66.4% of cell growth, respectively. Moreover, in vivo131I therapy further demonstrated that the growth of triple negative breast cancer (TNBC) was controlled by BMSC-Egr1-hNIS + AuNCs group, with relative volume inhibition percentages of 56.16% (compared with the control group) and 36.20% (compared with the BMSC-Egr1-hNIS group), respectively. To summarize, we successfully prepared BMSC-Egr1-hNIS carrying GSH@AuNCs to target TNBC which could synergistically improve the efficacy of hNIS gene therapy.

A Report on Health Resource Use in Internal Radiation Therapy with 131I-MIBG

Internal radiation therapy using 3-iodobenzylguanidine (131I) injection (131I-MIBG injection) will be applied in actual clinical practice soon. However, the NHI medical technical fee for the use of 131I-MIBG injection has not yet been set. The Japanese Society of Nuclear Medicine surveyed health resource use for internal radiation therapy using 131I via questionnaires sent to medical institutions that have used 131I-MIBG injection. Results showed that the necessary cost per patient is 1,912,671 JPY, which was based on the Draft Proposal for Medical Examination Value (Ver. 7.2) of the Japanese Health Insurance Federation for Surgery. 131I-MIBG injection is supposed to be administered once to each patient and the patient is followed up for 4 months after administration. The fee per treatment is calculated to be 478,168 JPY per month. The appropriate NHI medical technical fee is thus considered to be 47,817 points per month per patient per treatment, which can be claimed up to 4 times.

Biodistribution of 131I in mice is influenced by circadian variations

Effects of radiation and biodistribution of radionuclides are often studied in animal models. Circadian rhythm affects many biological functions and may influence the biokinetics of radionuclides and observed responses. The aim of this study was to investigate if the time during the day of 131I injection affects the biodistribution and absorbed dose to tissues in mice. Biodistribution studies were conducted on male C57BL/6 N mice for three diurnal time-series: the animals were i.v. injected with 160 kBq 131I at 8 am, 12 pm or 4 pm. The activity concentration in organs and tissues was measured at 1 h to 7 days after administration and absorbed dose at day 7 was determined. Comparison between the three time-series showed statistically significant differences in activity concentration in all investigated tissues and organs. Administration performed at 12 pm resulted in general in higher absorbed dose to the organs than injection performed at 8 am and 4 pm. Time of day of administration affects the biodistribution of 131I in mice and consequently the absorbed dose to individual organs. These findings advocate that subsequent biodistribution studies and dosimetry calculations should consider time-point of administration as a variable that could influence the results.

Class III PI3K Vps34 Controls Thyroid Hormone Production by Regulating Thyroglobulin Iodination, Lysosomal Proteolysis, and Tissue Homeostasis.

Background: The production of thyroid hormones [triiodothyronine (T3), thyroxine (T4)] depends on the organization of the thyroid in follicles, which are lined by a monolayer of thyrocytes with strict apicobasal polarity. This polarization supports vectorial transport of thyroglobulin (Tg) for storage into, and recapture from, the colloid. It also allows selective addressing of channels, transporters, ion pumps, and enzymes to their appropriate basolateral [Na+/I- symporter (NIS), SLC26A7, and Na+/K+-ATPase] or apical membrane domain (anoctamin, SLC26A4, DUOX2, DUOXA2, and thyroperoxidase). How these actors of T3/T4 synthesis reach their final destination remains poorly understood. The PI 3-kinase isoform Vps34/PIK3C3 is now recognized as a main component in the general control of vesicular trafficking and of cell homeostasis through the regulation of endosomal trafficking and autophagy. We recently reported that conditional Vps34 inactivation in proximal tubular cells in the kidney prevents normal addressing of apical membrane proteins and causes abortive macroautophagy. Methods:Vps34 was inactivated using a Pax8-driven Cre recombinase system. The impact of Vps34 inactivation in thyrocytes was analyzed by histological, immunolocalization, and messenger RNA expression profiling. Thyroid hormone synthesis was assayed by 125I injection and plasma analysis. Results:Vps34 conditional knockout (Vps34cKO) mice were born at the expected Mendelian ratio and showed normal growth until postnatal day 14 (P14), then stopped growing and died at ∼1 month of age. We therefore analyzed thyroid Vps34cKO at P14. We found that loss of Vps34 in thyrocytes causes (i) disorganization of thyroid parenchyma, with abnormal thyrocyte and follicular shape and reduced PAS+ colloidal spaces; (ii) severe noncompensated hypothyroidism with extremely low T4 levels (0.75 ± 0.62 μg/dL) and huge thyrotropin plasma levels (19,300 ± 10,500 mU/L); (iii) impaired 125I organification at comparable uptake and frequent occurrence of follicles with luminal Tg but nondetectable T4-bearing Tg; (iv) intense signal in thyrocytes for the lysosomal membrane marker, LAMP-1, as well as Tg and the autophagy marker, p62, indicating defective lysosomal proteolysis; and (v) presence of macrophages in the colloidal space. Conclusions: We conclude that Vps34 is crucial for thyroid hormonogenesis, at least by controlling epithelial organization, Tg iodination as well as proteolytic T3/T4 excision in lysosomes.

Human sodium iodide transporter gene-mediated imaging and therapy of mouse glioma, comparison between 188Re and 131I.

Novel treatment options are urgently required for patients with glioma who are not effectively treated through standard therapy. Human sodium iodide symporter (hNIS) is a molecular target of certain tumors types. Compared with 131I, 188Re possesses a higher energy and shorter half-life; therefore, the effects of 188Re and 131I were compared in hNIS-mediated gene imaging and therapy in the present study. Recombinant human brain glioma cell line U87 was transfected with a recombinant lentiviral vector containing hNIS (U87-hNIS). U87-0 cell line transfected with blank lentivirus was prepared as a control. In vitro, the 188Re and 131I uptake of U87-hNIS cells were 21.3-times and 25.9-times that of the control groups, however the excretion rate of the two nuclides was very rapid, and the half-life was only ~4 min. Sodium perchlorate inhibited hNIS-mediated 188Re and 131I uptake to levels observed in the control groups. 188Re and 131I were able to kill U87-hNIS cells selectively, with a survival of only 21.6 and 36.2%, respectively. U87-hNIS nude mice appeared to accumulate 188Re, with a ratio of radioactivity counts between tumor and non-tumor sites of ~13.5 compared with 10.3 of 131I 1 h after radionuclide injection. In contrast with in vitro studies, U87-hNIS cells demonstrated a notable increase in 188Re retention in vivo, even 24 h after 188Re injection. U87-hNIS cells also exhibited increased 131I retention in vivo; however, as the time increased, 131I was rapidly released with the tumor no longer able to be imaged 24 h after 131I injection. Following treatment, U87-hNIS tumors experienced a volume reduction of 24.1%, whereas U87-0 cells demonstrated an increase of 28.8%. 188Re and 131I were revealed to be effective at decreasing tumor volume compared with the control. However, 188Re was significantly more potent compared with 131I (P<0.01). The present study indicated that the U87-hNIS cell line is sufficient to induce specific 188Re and 131I uptake, which may kill cells in vitro and in vivo. 188Re exhibited an increased retention time in vivo compared with 131I, which facilitates the imaging and therapy of U87-hNIS tumors.

Quantitative Measurement of the Thyroid Uptake Function of Mouse by Cerenkov Luminescence Imaging

Cerenkov luminescence imaging (CLI) has been an evolutional and alternative approach of nuclear imaging in basic research. This study aimed to measure the 131I thyroid uptake of mouse using CLI for assessment of thyroid function. Quantification of 131I thyroid uptake of mice in euthyroid, hypothyroid and hyperthyroid status was performed by CLI and γ-scintigraphy at 24 hours after injection of 131I. The 131I thyroid uptake was calculated using the equation: (thyroid counts − background counts)/(counts of injected dose of 131I) × 100%. Serum T4 concentration was determined to evaluate the thyroid function. The radioactivity of 131I was linearly correlated with the CL signals in both in vitro and in vivo measurements. CLI showed a significant decrease and increase of 131I thyroid uptake in the mice in hypo- and hyperfunctioning status, respectively, and highly correlated with that measured by γ-scintigraphy. However, the percent thyroid uptake measured by CLI were one-fifth of those measured by γ-scintigraphy due to insufficient tissue penetration of CL. These results indicate that CLI, in addition to nuclear imaging, is able to image and evaluate the 131I thyroid uptake function in mice in preclinical and research settings.

Gefitinib enhances radiotherapeutic effects of 131I–hEGF targeted to EGFR by increasing tumor uptake of hEGF in tumor xenografts

Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has been proven effective for cancer treatment. In this study, we sought to determine whether gefitinib could increase the in vivo tumor uptake of human 131I–EGF (131I–hEGF), thereby enhancing the potential of hEGF as a vehicle for EGFR-targeted radionuclide therapy. Western blot analysis was conducted to detect the effects of gefitinib on EGFR expression in human head and neck squamous carcinoma cell line UM-SCC-22B. Nude mice bearing UM-SCC-22B tumor xenografts were pretreated via i.p. injection of gefitinib or DMSO (vehicle control), followed by i.v. injection of 125I–hEGF; the animals were then subjected to ex vivo biodistribution or injection of 131I–hEGF for planar γ-imaging using SPECT, respectively. Targeted radionuclide therapy using 131I–hEGF combined with gefitinib as a vehicle targeting EGFR was also performed in UM-SCC-22B tumor xenografts. The EGFR level was unchangeable in cells pretreated with gefitinib, but after gefitinib pretreatment, the uptake of 125I–hEGF in 22B tumor xenografts increased substantially while the uptake of 125I–hEGF in normal organs was effectively unchanged. 131I–hEGF as a vehicle for EGFR-targeting therapy combined with gefitinib therefore showed strong therapeutic effects against 22B tumor xenografts tolerant to gefitinib. The uptake of hEGF to EGFR-positive tumors was enhanced significantly after gefitinib pretreatment, suggesting that 131I–hEGF is a potential vehicle for EGFR-targeting radionuclide therapy when combined with gefitinib.

Improved therapeutic outcomes of thermal ablation on rat orthotopic liver allograft sarcoma models by radioiodinated hypericin induced necrosis targeted radiotherapy.

Residual tumor resulting in tumor recurrence after various anticancer therapies is an unmet challenge in current clinical oncology. This study aimed to investigate the hypothesis that radioiodinated hypericin (131I-Hyp) may inhibit residual tumor recurrence after microwave ablation (MWA) on rat orthotopic liver allograft sarcoma models.Thirty Sprague-Dawley (SD) rats with hepatic tumors were divided into three groups: Group A received laparotomy MWA and sequential intravenous injection (i.v.) of 131I labelled hypericin (131I-Hyp) in a time interval of 24 h; Group B received only laparotomy MWA; Group C was a blank control. Tumor inhibitory effects were monitored with in vivo magnetic resonance imaging (MRI) and these findings were compared to histopathology data before (baseline, day 0) and 1, 4, and 8 days after MWA. In addition, biodistribution of 131I-Hyp was assessed with in vivo single-photon emission computed tomography-computed tomography (SPECT-CT) imaging, in vitro autoradiography, fluorescent microscopy, and gamma counting.A fast clearance of 131I-Hyp and increasing deposit in necrotic tumors appeared over time, with a significantly higher radioactivity than other organs (0.9169 ± 1.1138 % ID/g, P < 0.01) on day 9. Tumor growth was significantly slowed down in group A compared to group B and C according to MRI images and corresponding tumor doubling time (12.13 ± 1.99, 4.09 ± 0.97, 3.36 ± 0.72 days respectively). The crescent tagerability of 131I-Hyp to necrosis was visualized consistently by autoradiography and fluorescence microscopy.In conclusion, 131I-Hyp induced necrosis targeted radiotherapy improved therapeutic outcomes of MWA on rat orthotopic liver allograft sarcoma models.

PROLACTIN BINDING SITES IN XENOPUS LAEVIS (DAUDIN) (ANURA PIPIDAE) KIDNEY: AN AUTORADIOGRAPHIC AND IMMUNOCYTOCHEMICAL STUDY

SUMMARY We have studied prolactin binding sites in Xenopus laevis (Daudin) (Anura Pipidae) kidney by autoradiography and immunocytochemistry. By the autoradiographic technique after intracardiac injection of 125I- oPRL labelling is appreciable in Xenopus laevis kidney at the level of the large vessels and capillaries, the renal corpuscle and, to a variable extent, within the lumina and epithelial cells of the proximal convoluted tubules. Compared to the autoradiographic reaction, the immunocytochemical method failed to reveal the hormone when extremely low doses of it were injected but allowed a much more exact localization of prolactin uptake by the epithelial cells of the proximal convoluted tubules. On the basis of the autoradiographs we could not ascertain wheter, or to what extent, the hormone was bound to specific renal cell PRL receptors: in fact, not only insulin and luteinizing hormone, but also unlabelled prolactin, injected as a specific competitor, failed to bring about the recognizable displa...

Radionuclide imaging and therapy mediated by hNIS gene transfection in nasopharyngeal carcinoma xenograft model

Objective To explore the feasibility of 131I radiotherapy mediated by hNIS gene trans- fection in nasopharyngeal carcinoma （NPC）. Methods NPC xenograft models were established with CNE- 2-hNIS cells （experimental group） and CNE-2 cells （control group）. Radioactivity of different organs of nude mice was counted at 0.5, 1,2, 6 and 24 h after intraperitoneal injection of 125I using a gamma counter. 99TcmO4 imaging was also performed in nude mice. Changes in the xenograft tumor volume were ob- served after 131I treatment in the experimental group and control group. Cell apoptosis was detected after 131I treatment by the terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling （TUNEL） method and caspase 3 and Ki67 expressions measured with immunohistochemistry of the tumor tissue. Statis- tical analysis was performed using SPSS 13.0 software, and the mean values between groups were compared using t test. Results CNE-2-hNIS and CNE-2 NPC xenografts were established successfully in nude mice. Biodistribution of 125I in tumor-bearing nude mice showed enhanced tumor uptake of 125I in the experimental group, with peak uptake at 1 h （ （20.28 ±0.15）% ）. The biological half-life of ^125I in the tumors transfect- ed with hNIS was about 1.56 h. Imaging studies showed that the tumors in the experimental group accumu- lated 99TcmO4- with a peak at 1.5 -2 h, whereas the control tumors were not visualized. The mean volume of the experimental xenograft tumors was （0.44 ± 0.04） cm3 before in I treatment and increased to （0.97± 0.08） cm3 after 1311 treatment. However, the volume of the control xenografts was （0.45± 0.06） cm3 before 131I treatment and （2.98 ±0.16） cm3 after 131I treatment. The tumor volume of the experimental group was significantly smaller compared with that of the control group after ~311 treatment （ t = 19.46, P 〈 0.01 ）. A higher apoptotic index and caspase 3 positive rate as well as lower Ki67 proliferation index were observed in the experimental group after 131I treatment （（0.66 ± 0.07）%, （0.56 ± 0.14）%, （0.22± 0.10）%, respectively） compared with those before ^131I treatment （ （0.08±0.06） %, （0. 13 ± 0.04） % and （0.65±0.11 ） %, t = 10.89, 5.12, 5.01, respectively, all P 〈 0.05）. Conclusions The transfected hNIS gene may mediate uptake of 125I, 131I and 99Tcm 04 in NPC xenografts and thus provides potential for radionuclide imaging and radiotherapy for NPC. 131i may effectively inhibit proliferation and induce apoptosis of NPC xen- ografts transfected with the hNIS gene. Key words: Nasopharyngeal neoplasms ; Neoplasm transplantation ; Transfection ; Sodium/iodide symporter; Radionuclide imaging; Brachtherapy; Mice, nude

Influence of water level on oil–water separation by residence time distribution curves investigations

The separation of crude oil and water mixtures is an important process in the oil and chemical industries. This work studied the flow behavior of crude oil and water in a pilot scale oil–water separator. This gravity separator (diameter of 1.2 m and length of 5.2 m) was operated by Drood oil of the Iranian Offshore Oil Company (IOOC) located in Kharg Island (Iran). The residence time distribution (RTD) curves were acquired in this separator by radioactive tracer ( 131I) injection. Experimental results showed that the separator operational performance increased with the water level in the vessel. Perfect mixing tanks-in-series (with a dead zone) have been used to describe the liquid behavior, and the experimental results were in good agreement with this model. Increasing the water level in the vessel from 0.5 m to 0.9 m increases the number of mixing tanks-in-series of both organic and aqueous phases, from 9.0 to 9.1 and from 8 to 8.3, respectively. The dead volume of the organic phase path decreased with water level, but this trend was reversed for the aqueous phase path. Less than 3% of the volume of the separator is active. The separator’s optimum efficiency occurred when the water level in the separator was about 0.7 m.

Thyroid hormone receptor α1–β1 expression in epididymal epithelium from euthyroid and hypothyroid rats

The objectives of the present work were to assess whether epithelial cells from the different segments of epididymis express TR alpha 1-beta 1 isoforms, to depict its subcellular immunolocalization and to evaluate changes in their expression in rats experimentally submitted to a hypothyroid state by injection of 131I. In euthyroid and hypothyroid groups, TR protein was expressed in epididymal epithelial cells, mainly in the cytoplasmic compartment while only a few one showed a staining in the nucleus as well. A similar TR immunostaining pattern was detected in the different segments of the epididymis. In hypothyroid rats, the number of TR-immunoreactive epithelial cells as well as the intensity of the cytoplasmic staining significantly increased in all sections analyzed. In consonance to the immunocytochemical analysis, the expression of TR alpha 1-beta 1 isoforms, assessed by Western blot revealed significantly higher levels of TR in cytosol compared to the nuclear fractions. Furthermore, TR expression of both alpha 1 and beta 1 isoforms and their mRNA levels were increased by the hypothyroid state. The immuno-electron-microscopy showed specific reaction for TR in principal cells associated with eucromatin, cytosolic matrix and mitochondria. The differences in expression levels assessed in control and thyroidectomized rats ascertain a specific function of TH on this organ.

Maternal leptin treatment during lactation programs the thyroid function of adult rats

Recently, we showed that both maternal malnutrition during lactation and leptin treatment during the neonatal period program thyroid function. In this study we evaluate whether maternal leptin treatment during lactation programs thyroid function of the offspring in the adulthood. The dams were divided into 2 groups: Lep-daily sc single injected with 8 μg/100 g of body weight with recombinant rat leptin during the last 3 days of lactation and control group (C) that received the same volume of saline. The 180 day-old animals received a single i.p. injection of 125I (2.22 × 10 4 Bq) and they were killed 2 h after the injection. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) and leptin concentrations were measured by radioimmunoassay. The milk of leptin-treated mothers on the last day of treatment had higher leptin ( p < 0.05) concentration. The pups of the leptin-treated mothers had at 21 days an unchanged T3, T4 and leptin serum concentrations with higher TSH ( p < 0.05). The offspring of Lep mothers had at 180 days a higher T3 ( p < 0.05) with normal thyroid 125I uptake, T4 and TSH serum concentrations compared to the controls. So, the mother's hyperleptinaemia during lactation programs to a higher T3 serum concentration on the offspring, probably by a higher leptin transfer through the milk.

Using anti-VEGF McAb and magnetic nanoparticles as double-targeting vector for the radioimmunotherapy of liver cancer

To study the biodistribution of a new radioimmunoconjugate— 131I–anti-VEGF monoclonal antibody (Sc-7269)–Dextran Magnetic Nanoparticles (DMN) in nude mice bearing human liver cancer where an external magnetic field was focused on, and to evaluate its therapeutic effects and safety. Tumor Growth Delay (TGD) and tumor inhibition rate were observed as antitumor effect. Peripheral white blood cells counts and the loss of body weight were tested as an indicator of systemic toxicity. The results suggests that the radioimmunotherapy of intratumoral injection of 131I–Sc-7269–DMN may be safe and efficient for the treatment of liver cancer. Furthermore, the radioimmunotherapy using DMN as a ‘carrier system’ may be a highly potential approach in the treatment of other kind of tumors.

Leptin treatment during lactation increases transfer of iodine through the milk

We have previously shown that protein restriction during lactation is associated with changes in iodine secretion into the milk and that a pup's serum leptin concentration was increased at the end of lactation. So, here we evaluate whether leptin treatment during lactation affects iodine transfer through the milk to the pups. Lactating rats were divided into two groups: the leptin (Lep) group, single injected with recombinant rat leptin (8 μg/100g of body weight, daily for 3 consecutive days), and the control (C) group that received the same volume of saline. We studied iodine transfer to the pups through the milk on Days 4, 12 and 21 of lactation. In those days, the dams were separated from their pups for 4 h. Then, the mothers received an injection of 131I (2.22×10 4 Bq ip) and the pups were allowed to nurse for 2 h. The animals were sacrificed 2 h later. Leptin, total serum T3 and total serum T4 concentrations were higher ( P<.05) in pups of Lep mothers only on Day 4, suggesting a higher transfer of leptin through the milk at this period, probably with a direct stimulatory effect on thyroid hormone secretion. In other periods, however, even without a detectable increase in a pup's serum leptin concentration, maternal leptin administration increased the pup's thyroid iodine uptake (Day 12, 39%; Day 21, 34%), probably caused by a higher transfer of iodine through the milk, since they had a higher gastric content of 131I on Days 12 (31%) and 21 (128%).

Adenovirus biodistribution and noninvasive imaging of gene expression in vivo by positron emission tomography using human sodium/iodide symporter as reporter gene.

Amongst the various methods that can be developed for noninvasive monitoring of gene expression in vivo, the use of positron emission tomography (PET) appears to be the most promising both for preclinical and clinical studies. Various genes have been described as potential PET reporters, but there is a need to develop new approaches that exploit transgenes with both therapeutic and imaging potential. The Na/I symporter (NIS) gene is expressed mainly in the thyroid and is responsible for iodide accumulation in this organ. The NIS gene has been used in gene therapy experimentation. Ectopic expression of this gene in various type of malignant cells has led to radiosensitization and in some cases tumor regression in xenograft models in nude mice, highlighting the therapeutic potential of this approach. In the present study, we demonstrate the potential of the human NIS gene (hNIS) as a reporter gene. Expression of hNIS, after plasmid transfection or adenoviral gene delivery, can be monitored in vitro on incubation with (125)I. Iodide uptake in the transduced cells can be directly correlated with the levels of gene expression in vitro. Ectopic expression of the NIS gene in vivo can be monitored in biodistribution studies on intravenous injection of (125)I. Adenovirus delivery induces gene expression essentially in the liver, adrenal glands, lungs, pancreas, and spleen. Expression of hNIS in tumor xenograft models can also be detected when the virus is injected intratumorally. Finally, hNIS expression was monitored by PET after intravenous injection of (124)I, demonstrating the potential of this approach for noninvasive imaging.

In vitro and in vivo characteristics of a human colon cancer cell line, SNU-C5N, expressing sodium-iodide symporter

Rat NIS (rNIS) genes were transfected into a human colon cancer cell line (SNU-C5) by lipofection. The transfected cells (SNU-C5N) exhibited an increase 125I uptake to a level 10 times higher than the untransfected SNU-C5 cells. The addition of 300 μM DIDS, an anion channel blocker, to the culture media led to a 2.35 times increase of 125I uptake in the cells. For the first 10 minutes, up to 70% of the cellular radioactivity was released into the medium. In the biodistribution study using SNU-C5N-xenografted mice, the %ID/g of the SNU-C5N tumors at 1, 3, 6, and 12 h after the 125I injection were 4.43%, 1.09%, 1.05%, and 0.05%, respectively, which were significantly higher than those for the SNU-C5 tumors ( P<0.05). In tumor imaging, the SNU-C5N-xenografted tumor was clearly visible. In this study, NIS lipofection is efficient for triggering significant iodide uptake by a nonthyroidal tumor. However, for an increased therapeutic effect, the key issue is iodide retention in the target tissue.

The effect of AVP-V2 receptor stimulation on local GFR in the rat kidney.

The effect of AVP-V2 receptor agonist desmopressin, dDAVP, its non-peptide antagonist OPC-31260 and vehicle infusion on glomerular filtration rate (GFR) in the outer, middle and inner cortex was studied in both hydropenic and water diuretic Inactin anaesthetized female Sprague-Dawley rats using the aprotinin method. Two subsequent GFR measurements were carried out in the same kidney by injection of 125I- and 131I-labelled aprotinin before and after i.v. infusion of dDAVP, OPC-31260 or the vehicle. Acute infusion of dDAVP in hydropenic rats increased total GFR by 14% relative to vehicle infusion, whereas in water diuretic rats it had no effect relative to vehicle. No significant changes in arterial pressure (Pa) or renal blood flow (RBF) were recorded. Infusion of OPC-31260 reduced total GFR by 11% compared with vehicle. These results are consistent with the findings that a presensitization of the vasculature by high plasma levels of AVP is necessary for the renal vascular effects mediated by the V2 or V2-like receptors to occur. The ratio between inner and outer cortex GFR remained unchanged from control to experimental condition as follows: dDAVP infusion in hydropenic rats, 0.504 vs. 0.494 in control; vehicle infusion in hydropenic rats, 0. 393 vs. 0.392; OPC-31260 infusion in hydropenic rats, 0.517 vs. 0. 523; dDAVP in water diuretic rats, 0.547 vs. 0.543; vehicle in water diuretic rats, 0.413 vs. 0.417. Thus no significant difference in the GFR response was observed between superficial and deep cortical layers of the rat kidney.

The influence of low doses 131I-induced maternal hypothyroidism on the development of rat embryos

The aim of our research was to create and verify a model for studying the effects of a low dose of 131I and 131I-induced maternal hypothyroidism on the development of the embryo's thyroid gland and brain. The given dose (150 microCi) corresponds to the absorbed dose of 0.5 Gy. This dose is similar to that dose received by large numbers of the population of the C.I.S. regions polluted by radioactive isotopes of iodine as a result of the Chernobyl accident in 1985. Thirty-five female Wistar rats and their 168 newborn pups were used for observation. The females were divided into a control group and four experimental groups (each distinguished by the time of 131I injection: group I - no less than 12 days before mating; groups II, III and IV - on 5th, 10th and 16th days of gestation, respectively). In all the experimental female groups the incorporate dose of 131I led to hypothyroidism accompanied by a 43% reduction in the thyroxin level and by a nearly 8-fold increase in the TSH level. However, the influence of maternal hypothyroidism on the development of the thyroid gland and brain of embryos depends on the time when 131I took effect. There is a reduction in the weight of the newborns' brain and thyroid gland, total body mass. The hormonal status of the newborns' thyroid gland also changes. The proposed model will allow us to study many aspects of induced changes in the brain and thyroid gland of the embryos which develop under conditions of maternal hypothyroidism resulting from a low dose of 131I, administered at the critical times of development.