Phosphorus kinetics in lambs experimentally infected with Trichostrongylus colubriformis with the use of 32P.

This study was conducted to evaluate the metabolism and phosphorus (P) kinetics in lambs experimentally infected with Trichostrongylus colubriformis using the isotope dilution technique and modelling. Fifteen male lambs (21.1 ±â€¯1.50 kg) of the Santa Inês hair breed of approximately six months old, distributed in the treatments infected (I, n = 8) and control (C, n = 7) were used. The infected lambs received serial infections with 5000 T. colubriformis larvae, three times per week, for 3 weeks (45 000 T. colubriformis total larvae). After 66 days of the last inoculation of infective larvae, 6.6 MBq of 32P were injected in each lamb to evaluate the P kinetics. Blood, faeces and urine samples were collected in the following seven days and the slaughter of lambs were carried out on the last day in order to collect bone and soft tissues (Liver, kidney, heart and muscle) samples. To analyse P flows, the biomathematical model with four compartments (C1 - gastrointestinal tract, C2 - plasma, C3 - bone and C4 - soft tissue) was used. Similar P intake (VI) between treatments (C and I) was verified. Lower absorption of endogenous (Vaf) and dietary P (Vaa), as well as, lower amount of endogenous P (from saliva) that reaches the gastrointestinal tract (VIT), consequently, higher excretion of dietary P (VFD) were verified in infected lambs (P < 0.1). Additionally, in infected lambs, the P bioavailability was lower compared to control lambs. With the lower absorption (VaT) of P in infected lambs, there was, consequently, lower distribution to bones and soft tissues (VeD2) and lower P deposition in the bones (VO+D). It was concluded that P metabolism of lambs infected with T. colubriformis was altered, with reduced intestinal absorption and bioavailability, increased faecal loss and reduced P flow to the bone.

Evaluating the Application of Tissue-Specific Dose Kernels Instead of Water Dose Kernels in Internal Dosimetry: A Monte Carlo Study.

PURPOSE: The aim of this work is to evaluate the application of tissue-specific dose kernels instead of water dose kernels to improve the accuracy of patient-specific dosimetry by taking tissue heterogeneities into consideration. MATERIALS AND METHODS: Tissue-specific dose point kernels (DPKs) and dose voxel kernels (DVKs) for yttrium-90 (90Y), lutetium-177 (177Lu), and phosphorus-32 (32P) are calculated using the Monte Carlo (MC) simulation code GATE (version 7). The calculated DPKs for bone, lung, adipose, breast, heart, intestine, kidney, liver, and spleen are compared with those of water. The dose distribution in normal and tumorous tissues in lung, liver, and bone of a Zubal phantom is calculated using tissue-specific DVKs instead of those of water in conventional methods. For a tumor defined in a heterogeneous region in the Zubal phantom, the absorbed dose is calculated using a proposed algorithm, taking tissue heterogeneity into account. The algorithm is validated against full MC simulations. RESULTS: The simulation results indicate that the highest differences between water and other tissue DPKs occur in bone for 90Y (12.2% ± 0.6%), 32P (18.8% ± 1.3%), and 177Lu (16.9% ± 1.3%). The second highest discrepancy corresponds to the lung for 90Y (6.3% ± 0.2%), 32P (8.9% ± 0.4%), and 177Lu (7.7% ± 0.3%). For 90Y, the mean absorbed dose in tumorous and normal tissues is calculated using tissue-specific DVKs in lung, liver, and bone. The results are compared with doses calculated considering the Zubal phantom water equivalent and the relative differences are 4.50%, 0.73%, and 12.23%, respectively. For the tumor in the heterogeneous region of the Zubal phantom that includes lung, liver, and bone, the relative difference between mean calculated dose in tumorous and normal tissues based on the proposed algorithm and the values obtained from full MC dosimetry is 5.18%. CONCLUSIONS: A novel technique is proposed considering tissue-specific dose kernels in the dose calculation algorithm. This algorithm potentially enables patient-specific dosimetry and improves estimation of the average absorbed dose of 90Y in a tumor located in lung, bone, and soft tissue interface by 6.98% compared with the conventional methods.

Phosphorylation of phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxylase (PEPC) in the flesh of fruits.

This study determined whether phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxylase (PEPC) are phosphorylated in the flesh of a range of fruits. This was done by incubating fruit flesh with 32P[P] (where 32P[P] = 32PO43-), then PEPCK and PEPC were immunoprecipitated from extracts using specific antisera. The incorporation of 32P[P] into these enzymes was then determined by autoradiography of SDS-PAGE gels. Both enzymes were subject to phosphorylation in vivo in the flesh of grape, tomato, cherry and plum. PEPCK was also subject to phosphorylation in vivo in developing grape seeds. Proteolytic cleavage of PEPCK showed that it was phosphorylated at a site(s) located on its N-terminal extension. Potentially phosphorylation of these enzymes could contribute to the coordinate regulation of their activities in the flesh of fruits and in developing seeds.

Technical Note: Impact of cell repopulation and radionuclide uptake phase on cell survival.

PURPOSE: To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. METHODS: The instantaneous-uptake model of O'Donoghue ["The impact of tumor cell proliferation in radioimmunotherapy," Cancer 73, 974-980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). RESULTS: Surviving fractions are calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1-24 h, extrapolated initial dose-rates 0.5-1 Gy h(-1), and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy(-1). It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient. CONCLUSIONS: The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.

Isolation of Catharanthus roseus (L.) G. Don Nuclei and Measurement of Rate of Tryptophan decarboxylase Gene Transcription Using Nuclear Run-On Transcription Assay.

BACKGROUND: An accurate assessment of transcription 'rate' is often desired to describe the promoter activity. In plants, isolation of transcriptionally active nuclei and their subsequent use in nuclear run-on assays has been challenging and therefore limit an accurate measurement of gene transcription 'rate'. Catharanthus roseus has emerged as a model medicinal plant as it exhibits an unsurpassed spectrum of chemodiversity, producing over 130 alkaloids through the terpenoid indole alkaloid (TIA) pathway and therefore serves as a 'molecular hub' to understand gene expression profiles. RESULTS: The protocols presented here streamline, adapt and optimize the existing methods of nuclear run-on assay for use in C. roseus. Here, we fully describe all the steps to isolate transcriptionally active nuclei from C. roseus leaves and utilize them to perform nuclear run-on transcription assay. Nuclei isolated by this method transcribed at a level consistent with their response to external stimuli, as transcription rate of TDC gene was found to be higher in response to external stimuli i.e. when seedlings were subjected to UV-B light or to methyl jasmonate (MeJA). However, the relative transcript abundance measured parallel through qRT-PCR was found to be inconsistent with the synthesis rate indicating that some post transcriptional events might have a role in transcript stability in response to stimuli. CONCLUSIONS: Our study provides an optimized, efficient and inexpensive method of isolation of intact nuclei and nuclear 'run-on' transcription assay to carry out in-situ measurement of gene transcription rate in Catharanthus roseus. This would be valuable in investigating the transcriptional and post transcriptional response of other TIA pathway genes in C. roseus. Isolated nuclei may also provide a resource that could be used for performing the chip assay as well as serve as the source of nuclear proteins for in-vitro EMSA studies. Moreover, nascent nuclear run-on transcript could be further subjected to RNA-Seq for global nuclear run-on assay (GNRO-Seq) for genome wide in-situ measurement of transcription rate of plant genes.

Amplification of the effects of magnetization exchange by (31) P band inversion for measuring adenosine triphosphate synthesis rates in human skeletal muscle.

PURPOSE: The goal of this study was to amplify the effects of magnetization exchange between γ-adenosine triphosphate (ATP) and inorganic phosphate (Pi) for evaluation of ATP synthesis rates in human skeletal muscle. METHODS: The strategy works by simultaneously inverting the (31) P resonances of phosphocreatine (PCr) and ATP using a wide bandwidth, adiabatic inversion radiofrequency pulse followed by observing dynamic changes in intensity of the noninverted Pi signal versus the delay time between the inversion and observation pulses. This band inversion technique significantly delays recovery of γ-ATP magnetization; consequently, the exchange reaction, Pi ↔ γ-ATP, is readily detected and easily analyzed. RESULTS: The ATP synthesis rate measured from high-quality spectral data using this method was 0.073 ± 0.011 s(-1) in resting human skeletal muscle (N = 10). The T1 of Pi was 6.93 ± 1.90 s, consistent with the intrinsic T1 of Pi at this field. The apparent T1 of γ-ATP was 4.07 ± 0.32 s, about two-fold longer than its intrinsic T1 due to storage of magnetization in PCr. CONCLUSION: Band inversion provides an effective method to amplify the effects of magnetization transfer between γ-ATP and Pi. The resulting data can be easily analyzed to obtain the ATP synthesis rate using a two-site exchange model.

Brain high-energy phosphates and creatine kinase synthesis rate under graded isoflurane anesthesia: An in vivo (31) P magnetization transfer study at 11.7 tesla.

PURPOSE: The creatine kinase rate of metabolic adenosine triphosphate (ATP) synthesis is an important metabolic parameter but is challenging to measure in vivo due to limited signal-to-noise ratio and long measurement time. THEORY AND METHODS: This study reports the implementation of an accelerated (31) P Four Angle Saturation Transfer (FAST) method to measure the forward creatine kinase (CK) rate of ATP synthesis. Along with a high-field scanner (11.7 Tesla) and a small sensitive surface coil, the forward CK rate in the rat brain was measured in ∼5 min. RESULTS: Under 1.2% isoflurane, the forward CK rate constant and metabolic flux were, respectively, kf , CK =0.26 ± 0.02 s(-1) and Ff,CK =70.8 ± 4.6 µmol/g/min. As a demonstration of utility and sensitivity, measurements were made under graded isoflurane. Under 2.0% isoflurane, kf , CK =0.16 ± 0.02 s(-1) and Ff,CK =410.0 ± 4.2 µmol/g/min, corresponding to a 38% and 42% reduction, respectively, relative to 1.2% isoflurane. By contrast, the ATP and phosphocreatine concentrations were unaltered. CONCLUSION: This study demonstrated the (31) P FAST measurement of creatine kinase rate of ATP synthesis in rat brain with reasonable temporal resolution. Different isoflurane levels commonly used in animal models significantly alter the CK reaction rate but not ATP and phosphocreatine concentrations.

Proposed biokinetic model for phosphorus.

This paper reviews data related to the biokinetics of phosphorus in the human body and proposes a biokinetic model for systemic phosphorus for use in updated International Commission on Radiological Protection (ICRP) guidance on occupational intake of radionuclides. Compared with the ICRP's current occupational model for systemic phosphorus (Publication 68, 1994), the proposed model provides a more realistic description of the paths of movement of phosphorus in the body and greater consistency with experimental, medical, and environmental data regarding its time-dependent distribution. For acute uptake of (32)P to blood, the proposed model yields roughly a 50% decrease in dose estimates for bone surface and red marrow and a six-fold increase in estimates for liver and kidney compared with the model of Publication 68. For acute uptake of (33)P to blood, the proposed model yields roughly a 50% increase in dose estimates for bone surface and red marrow and a seven-fold increase in estimates for liver and kidney compared with the model of Publication 68.

Root cortical aerenchyma inhibits radial nutrient transport in maize (Zea mays).

BACKGROUND AND AIMS: Formation of root cortical aerenchyma (RCA) can be induced by nutrient deficiency. In species adapted to aerobic soil conditions, this response is adaptive by reducing root maintenance requirements, thereby permitting greater soil exploration. One trade-off of RCA formation may be reduced radial transport of nutrients due to reduction in living cortical tissue. To test this hypothesis, radial nutrient transport in intact roots of maize (Zea mays) was investigated in two radiolabelling experiments employing genotypes with contrasting RCA. METHODS: In the first experiment, time-course dynamics of phosphate loading into the xylem were measured from excised nodal roots that varied in RCA formation. In the second experiment, uptake of phosphate, calcium and sulphate was measured in seminal roots of intact young plants in which variation in RCA was induced by treatments altering ethylene action or genetic differences. KEY RESULTS: In each of three paired genotype comparisons, the rate of phosphate exudation of high-RCA genotypes was significantly less than that of low-RCA genotypes. In the second experiment, radial nutrient transport of phosphate and calcium was negatively correlated with the extent of RCA for some genotypes. CONCLUSIONS: The results support the hypothesis that RCA can reduce radial transport of some nutrients in some genotypes, which could be an important trade-off of this trait.

(31) P MR spectroscopic imaging combined with (1) H MR spectroscopic imaging in the human prostate using a double tuned endorectal coil at 7T.

PURPOSE: Improved diagnostic sensitivity could be obtained in cancer detection and staging when individual compounds of the choline pool can be detected. Therefore, a novel coil design is proposed, providing the ability to acquire both (1) H and (31) P magnetic resonance spectroscopic imaging (MRSI) in patients with prostate cancer. METHODS: A two-element (1) H/(31) P endorectal coil was designed by adjusting a commercially available 3T endorectal coil. The two-element coil setup was interfaced as a transceiver to a whole body 7T MR scanner. Simulations and phantom measurements were performed to compare the efficiency of the coil. (1) H MRSI and (31) P MRSI were acquired in vivo in prostate cancer patients. RESULTS: The efficiency of the (1) H/(31) P coil is comparable to the dual channel (1) H coil previously published. Individually distinguishable phospholipid metabolites in the in vivo (31) P spectra were: phosphoethanolamine, phosphocholine, phosphate, glycerophosphoethanolamine, glycerophosphocholine, phosphocreatine, and adenosine triposphate. (1) H MRSI was performed within the same scan session, visualizing choline, polyamines, creatine, and citrate. CONCLUSION: (1) H MRSI and (31) P MRSI can be acquired in the human prostate at 7T within the same scan session using an endorectal coil matched and tuned for (1) H (quadrature) and (31) P (linear) without the need of cable traps and with negligible efficiency losses in the (1) H and (31) P channel.

Preliminary study of the biodegradation and the correlation between in vitro and in vivo release of (32)P-chromic phosphate-poly(L-lactide) seeds.

OBJECTIVE: To investigate the drug release kinetic of (32)P-chromic phosphate-poly(L-lactide) ((32)P-CP-PLLA). METHODS: (32)P-CP-PLLA were placed into physiological saline and H22 solid tumor mass, respectively. The weight loss rate and radioactivity release rate were evaluated. The release of the microparticles was evaluated using fitting curves. The correlation of the release of the microparticles between physiological saline and H22 solid tumor mass was analyzed. RESULTS: Close correlation was noted in the release of the microparticles between physiological saline and H22 solid tumor mass. The Weibull equation showed the best fitting of (32)P-CP-PLLA in physiological saline. CONCLUSIONS: The Weibull equation could be used for the predictive release of microparticles in vitro. The parameters obtained from the drug release kinetics could be used to estimate the dose of radiopharmaceuticals within the tumors and the surrounding tissues.

Unsupervised analysis of small animal dynamic Cerenkov luminescence imaging.

Clustering analysis (CA) and principal component analysis (PCA) were applied to dynamic Cerenkov luminescence images (dCLI). In order to investigate the performances of the proposed approaches, two distinct dynamic data sets obtained by injecting mice with (32)P-ATP and (18)F-FDG were acquired using the IVIS 200 optical imager. The k-means clustering algorithm has been applied to dCLI and was implemented using interactive data language 8.1. We show that cluster analysis allows us to obtain good agreement between the clustered and the corresponding emission regions like the bladder, the liver, and the tumor. We also show a good correspondence between the time activity curves of the different regions obtained by using CA and manual region of interest analysis on dCLIT and PCA images. We conclude that CA provides an automatic unsupervised method for the analysis of preclinical dynamic Cerenkov luminescence image data.

A facile, viable approach toward the preparation of 32p patches for the treatment of skin cancer.

A facile, viable, "green" two-step, inexpensive technique was developed for the preparation of (32)P patch for the treatment of skin cancer. This technique consists of impregnation of H(3)(32)PO(4) solution into an inert solid carrier followed by immobilization into a nonleachable matrix by lamination. The morphology of the impregnated paper was evaluated by scanning electron microscope and energy-dispersive spectral analyses. Radioactive patches containing up to ∼37 MBq/cm(2) of (32)P could be prepared. Distribution of (32)P on sources was uniform and release of (32)P from the sealed source in water and saline was found to be well within the permissible levels of 185 Bq. Custom-shaped (32)P-patches after quality assurance were supplied to AIIMS, New Delhi, for clinical evaluation. (32)P-impregnated paper protected by a laminated film holds promise for treatment of superficial cancers.

A review and model assessment of (32)P and (33)P uptake to biota in freshwater systems.

Bioaccumulation of key short-lived radionuclides such as (131)I and (32,33)P may be over-estimated since concentration ratios (CRs) are often based on values for the corresponding stable isotope which do not account for radioactive decay during uptake via the food chain. This study presents estimates for bioaccumulation of radioactive phosphorus which account for both radioactive decay and varying ambient levels of stable P in the environment. Recommended interim CR values for radioactive forms of P as a function of bioavailable stable phosphorus in the water body are presented. Values of CR are presented for three different trophic levels of the aquatic food chain; foodstuffs from all three trophic levels may potentially be consumed by humans. It is concluded that current recommended values of the CR are likely to be significantly over-estimated for radioactive phosphorus in many freshwater systems, particularly lowland rivers. Further research is recommended to field-validate these models and assess their uncertainty. The relative importance of food-chain uptake and direct uptake from water are also assessed from a review of the literature. It can be concluded that food-chain uptake is the dominant accumulation pathway in fish and hence accumulation factors for radioactive phosphorus in farmed fish are likely to be significantly lower than those for wild fish.

Absorbed dose profiles for (32)P, (90)Y, (188)Re, (177)Lu, (153)Sm and (169)Er: radionuclides used in radiosynoviortheses treatment.

The main objective of this paper was to obtain the absorbed dose profiles for radionuclides of frequent or potential use in radiosynoviortheses. These profiles reveal the absorbed dose per activity of injected radionuclide (Gy/h*MBq) in the synovial membrane and the articular cartilage. The researched radionuclides were (32)P, (90)Y, (188)Re, (177)Lu, (153)Sm and (169)Er. The therapeutic range of each radionuclides in synovial tissue were also calculated. This range determines the synovial thickness that can be sufficiently irradiated and thus successfully treated. The S values for the synovial membrane and articular cartilage were calculated using as a model a cylinder with the source uniformly distributed in its volume. The synovial membrane was simulated varying the radius of the cylinder (from 0.5cm to 9cm) and its height (from 0.01cm to 0.04cm). The area in the base of the cylinder represents different sizes of the synovial surface (small, medium and large joints). The height of the cylinder represents different stages of the progression of the rheumatoid arthritis. The same model was used to simulate the articular cartilage but, the source was uniformly distributed into a cylindrical slab (0.01cm height and 1cm of radius. The results obtained allow the estimation of the dose that will be delivered to the synovial membrane and the articular cartilage for different joint sizes and different stages of progression of the rheumatoid arthritis (RA).

Bioevaluation of 32P patch designed for the treatment of skin diseases.

OBJECTIVE: The objective of this study was to design and evaluate a 32P patch for the treatment of skin diseases. MATERIALS AND METHODS: The patch was prepared from chromic phosphate 32P and silicone. Bioelimination and biodistribution in healthy and treated animals, and the therapeutic efficacy of two treatment schemes (single dose and fractionated dose) in an animal model of skin cancer were studied. RESULTS: Based on the bioelimination and biodistribution studies, no leakage of 32P from the patch was observed. The treated tumors reduced their mean diameter compared to controls. The single-dose therapeutic scheme showed a higher number of complete and partial remissions compared to the fractionated scheme. These results were confirmed by histopathological analysis of the samples. CONCLUSION: The 32P patch was designed and produced according to specifications for the treatment of superficial lesions of the skin. Although the 32P patch is an open source, it behaves like a sealed one for use in brachytherapy treatments.

Evaluation of the biological transfer of 32P, 137Cs and 65Zn by fish in the Yenisei River.

The biological transfer of three radionuclides ((32)P, (137)Cs, (65)Zn) by fish in the Yenisei River (Central Siberia, Russia) was evaluated using a radioecological model. The modelling is based on the general ECOMOD methodology, where radionuclide behavior in an aquatic organism is linked with the processes of growth and metabolism, also with the concentrations of stable analogous elements in the organism, its food and the environment. The model was applied to explain the peculiarities of (32)P, (137)Cs and (65)Zn accumulation in different ecological groups of fish, including non-migratory and migratory fish, non-predatory and predatory fish species. The highest activity concentrations in non-migratory fish from the Yenisei River were found for (32)P. The accumulation of (32)P by fish was shown to depend on the fish size (age, weight); however, it did not depend on the trophic status of fish. The modelling approach was developed to evaluate the biological transfer of radionuclides by the migratory fish, which spend the most part of life in the Yenisei delta, inlet or bay, and go upstream the Yenisei River for spawning. The results of the ECOMOD model calculations are in good agreement with available measurement data.

Interference of three weed extracts on uptake of nutrient in three different varieties of paddy through radio tracer techniques.

Interference of three dominant weed extracts viz., Ageratum conyzoides L., Melilotus indica All. and Parthenium hysterophorus L. were examined on seed germination, seedling growth, and nutrient uptake (32P and 65Zn) in three different varieties (PD-10, PD-12 and PB) of paddy (Oryza sativa L.). Among the three different varieties irrespective of weed extracts, PD-10 and PD-12 were resistant and PB was susceptible in terms of seed germination, radicle length and plumule dry weight; and PD-12 and PB were resistant and susceptible, respectively, in terms of plumule length and total seedling dry weight. A. conyzoides caused maximum reduction in seed germination and M. indica in seedling growth in different varieties of paddy. The weed extracts interfered in uptake of both 32P and 65Zn and there was a gradual decrease in uptake of both nutrients with increasing concentration of extracts in both root and shoot. The uptake of 32P and 65Zn was more inhibitory with the extracts of A. conyzoides and M. indica, respectively in different varieties. The inhibition in seed germination, seedling growth and nutrient uptake may be due to the presence of phenolics and other secondary metabolities. The phenolics such as gallic, vanillic, protocatechuic and p-hydroxybenzoic acids were identified from these weed extracts.

Evidence that 99mTc-(V)-DMSA uptake is mediated by NaPi cotransporter type III in tumour cell lines.

In vivo studies have demonstrated that pentavalent technetium-99m dimercaptosuccinic acid [(99m)Tc-(V)-DMSA] may be a useful tumour imaging agent. Several studies have suggested that (99m)Tc-(V)-DMSA uptake may be related to the structural similarity between the (99m)Tc-(V)-DMSA core and the PO(4)(3-) anion. As phosphate ions enter cells via NaPi cotransporters, we investigated whether (99m)Tc-(V)-DMSA uptake is mediated by NaPi cotransporters. (99m)Tc-(V)-DMSA and phosphate uptake kinetics were compared in three cancer cell lines (MCF-7, G152 and MG-63) under several conditions (with and without sodium and NaPi cotransporter inhibitor and at different pH). Determination of molecular NaPi cotransporter mRNA expression was performed by reverse-transcriptase polymerase chain reaction (Rt-PCR) assay. Results obtained in the presence of NaPi inhibitor, in sodium-free medium and at alkaline pH showed that (99m)Tc-(V)-DMSA accumulation is linked to NaPi cotransporter functionality. MCF-7 and G152 exhibited the same tracer uptake, whereas MG-63 showed the highest phosphate accumulation and the lowest (99m)Tc-(V)-DMSA uptake. These results were in accordance with mRNA NaPi expression, i.e. all cell lines expressed NaPi type III but MG-63 also co-expressed NaPi type I. The total level of NaPi cotransporter was highly correlated with phosphate accumulation, while the level of type III was related to (99m)Tc-(V)-DMSA uptake. We have demonstrated that (99m)Tc-(V)-DMSA uptake is specifically mediated by NaPi type III in cancer cells.

Feasibility study and dosimetric assessment of radiolabeled drugs injected to the coronary arterial wall to prevent restenosis.

PURPOSE: Intramural delivery of a P-32 radiolabeled oligonucleotide (ODN) using an infiltrating catheter has been proposed recently to potentially reduce restenosis in coronary arteries and tested on a limited number of human subjects. However, because of the low efficiency of drug retention (approximately 2-5%) after the initial washout period from this technique, the dose levels to nontarget organs may be significant and thus may require a detailed investigation. The radiation dose distributions resulting from this technique is investigated using the MIRD formalism and Monte Carlo calculations. MATERIALS AND METHODS: The total activity of the P-32 ODN to be injected during treatment to deliver a therapeutic dose of approximately 30 Gy to the arterial wall is estimated taking into account the drug delivery efficacy of the infiltrating device (approximately 2-5% typical). Using pharmacokinetic data for P-32 ODN, we estimate the dose to healthy organs resulting from the systemic fraction that is released into the circulatory system during washout (>95% typical). Variabilities in the biological parameters are also identified as important sources of error in the prescribed dose. RESULTS: A limitation to this technique is the poor accuracy in delivering the prescribed dose due to variability in the amount of drug delivered. Dose to organs is also an important limitation. For example, our calculation indicate that approximately 37 MBq (1 mCi) of P-32 labeled ODN are needed to deliver 30 Gy to the arterial wall assuming a delivery efficiency of 2-5% and a 24-h residence time. This may result in doses of approximately 1 Gy to the spleen and 0.2-0.4 Gy to the liver, kidneys and lungs (95% confidence interval). CONCLUSION: This novel therapy suffers from serious limitations. It is doubtful that a therapeutic dose can be delivered accurately, safely and effectively to the arterial wall because of the poor delivery efficacy and extreme variability found in drug delivery experiments. Also, dose levels to healthy organs appears to be too high to recommend the use of this technique in human experiments.