Suppressive effect of Yokukansan on glutamate released from canine keratinocytes.

Background: Canine atopic dermatitis (CAD) is caused by skin barrier dysfunction due to allergen exposure. Excessive glutamate release in the skin is associated with delayed skin barrier function recovery and epidermal thickening and lichenification. Treatment with Yokukansan (YKS), a traditional Japanese medicine, reduces dermatitis severity and scratching behavior in NC/Nga mice by decreasing epidermal glutamate levels. However, the association between canine keratinocytes and glutamate and the mechanism by which YKS inhibits glutamate release from keratinocytes remains unknown. Aim: We aimed to investigate glutamate release from canine progenitor epidermal keratinocytes (CPEKs) and the inhibitory effect of YKS on this release. We also explored the underlying mechanism of YKS to enable its application in CAD treatment. Methods: Glutamate produced from CPEKs in the medium at 24 hours was measured. The measurement conditions varied in terms of cell density and YKS concentration. CPEKs were treated with a glutamate receptor antagonist (MK-801), a glutamate transporter antagonist (THA), and a glutamate dehydrogenase inhibitor (epigallocatechin gallate; EGCG), and the inhibitory effect of YKS, YKS + THA, MK-801, and EGCG on this release was determined. MK-801 and glutamate dehydrogenase inhibitor were tested alone, and THA was tested in combination with YKS. Finally, glutamine incorporated into CPEKs at 24 hours was measured using radioisotope labeling. Results: CPEKs released glutamate in a cell density-dependent manner, inhibited by YKS in a concentration-dependent manner. Moreover, YKS reduced the intracellular uptake of radioisotope-labeled glutamine in a concentration-dependent manner. No involvement of glutamate receptor antagonism or activation of glutamate transporters was found, as suggested by previous studies. In addition, EGCG could inhibit glutamate release from CPEKs. Conclusion: Our findings indicated that glutamate release from CPEKs could be effectively inhibited by YKS, suggesting the utility of YKS in maintaining skin barrier function during CAD. In addition, CPEKs are appropriate for analyzing the mechanism of YKS. However, we found that the mechanism of action of YKS differs from that reported in previous studies, suggesting that it may have had a similar effect to EGCG in this study. Further research is warranted to understand the exact mechanism and clinical efficacy in treating CAD.

Photopharmacological Applications for Cherenkov Radiation Generated by Clinically Used Radionuclides.

Translational photopharmacological applications are limited through irradiation by light showing wavelengths within the bio-optical window. To achieve sufficient tissue penetration, using wavelengths >500 nm is mandatory. Nevertheless, the majority of photopharmacological compounds respond to irradiation with more energetic UV light, which shows only a minor depth of tissue penetration in the µm range. Thus, we became interested in UV light containing Cherenkov radiation (CR) induced as a by-product by clinically employed radionuclides labeling specific tissues. Therefore, CR may be applicable in novel photopharmacological approaches. To provide evidence for the hypothesis, we verified the clinically established radionuclides 68Ga and 90Y but not 18F in clinically used activities to be capable of generating CR in aqueous solutions. We then investigated whether the generated CR was able to photoactivate the caged kinase inhibitor cagedAZD5438 as a photoresponsive model system. Herein, 21% uncaging of the model system cagedAZD5438 occurred by incubation with 90Y, along with a non-specific compound decomposition for 68Ga and partly for 90Y. The findings suggest that the combination of a clinically employed radionuclide with an optimized photoresponsive agent could be beneficial for highly focused photopharmacological therapies.

Magnetic Targeting of Nanotheranostics Enhances Cerenkov Radiation-Induced Photodynamic Therapy.

The interaction between radionuclides and nanomaterials could generate Cerenkov radiation (CR) for CR-induced photodynamic therapy (PDT) without requirement of external light excitation. However, the relatively weak CR interaction leaves clinicians uncertain about the benefits of this new type of PDT. Therefore, a novel strategy to amplify the therapeutic effect of CR-induced PDT is imminently required to overcome the disadvantages of traditional nanoparticulate PDT such as tissue penetration limitation, external light dependence, and low tumor accumulation of photosensitizers. Herein, magnetic nanoparticles (MNPs) with 89Zr radiolabeling and porphyrin molecules (TCPP) surface modification (i.e., 89Zr-MNP/TCPP) were synthesized for CR-induced PDT with magnetic targeting tumor delivery. As a novel strategy to break the depth and light dependence of traditional PDT, these 89Zr-MNP/TCPP exhibited high tumor accumulation under the presence of an external magnetic field, contributing to excellent tumor photodynamic therapeutic effect together with fluorescence, Cerenkov luminescence (CL), and Cerenkov resonance energy transfer (CRET) multimodal imaging to monitor the therapeutic process. The present study provides a major step forward in photodynamic therapy by developing an advanced phototherapy tool of magnetism-enhanced CR-induced PDT for effective targeting and treatment of tumors.

Combination of 177 Lu-lilotomab with rituximab significantly improves the therapeutic outcome in preclinical models of non-Hodgkin's lymphoma.

OBJECTIVES: To investigate the therapeutic potential of the next-generation anti-CD37 radioimmunoconjugate 177 Lu-lilotomab satetraxetan (177 Lu-lilotomab) in combination with the anti-CD20 antibody rituximab for treatment of mice with non-Hodgkin's lymphoma (NHL) xenografts. METHODS: Nude mice with subcutaneous (s.c.) Burkitt's lymphoma Daudi xenografts and SCID mice intravenously (i.v.) injected with Mantle cell lymphoma Rec-1 cells were treated with either 177 Lu-lilotomab or rituximab alone or with the combination of both treatments. Tumour volume, body weight, blood counts and clinical status were monitored. CD20 expression was measured using flow cytometry with fluorescence-labelled rituximab. RESULTS: The combination of 177 Lu-lilotomab and rituximab was synergistic for treatment of nude mice with s.c. Daudi xenografts while it was additive for treatment of SCID mice with i.v. injected Rec-1 cells. Binding of rituximab to NHL cells in-vitro was increased by pretreatment with 177 Lu-lilotomab. CONCLUSIONS: Treatment of mice with NHL xenografts with 177 Lu-lilotomab synergistically increased tumour suppression of subsequent anti-CD20 immunotherapy and improved survival. If the same effect is confirmed in a recently started clinical study, it could change the way radioimmunotherapy and CD20 immunotherapy would be used in the future.

In vitro demonstration of synergy/additivity between (188)rhenium and sorafenib on hepatoma lines: preliminary results.

BACKGROUND: Hepatocellular carcinoma is generally diagnosed at advanced stages, for which only palliative treatments are possible by intra-arterial route or by targeted therapies. Among these treatments, metabolic radiotherapy using (90)-yttrium or (188)Re and sorafenib are two options adopted in monotherapy. MATERIALS AND METHODS: We address the question of a possible synergy arising from the combination of these two treatments. Two primary malignant hepatoma cell lines, N1S1 (murine HCC) and HepG2 (human hepatoblastoma) were treated in media containing increasing concentrations of sorafenib with/without (188)Re to assess the cellular toxicities of each treatment alone and in combination. The combination index method was used to look for synergy or additivity. RESULTS: A synergistic advantage of a treatment combining (188)Re and sorafenib is shown in vitro on hepatoma cell lines. CONCLUSION: This combined approach is promising and now needs to be confirmed by more complex in vitro models integrating the tumoral stroma, as well as by in vivo studies.

Radium-223 chloride: Extending life in prostate cancer patients by treating bone metastases.

The treatment scope for patients with metastatic castrate-resistant prostate cancer (mCRPC) is rapidly expanding. On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium-223 chloride ((223)RaCl2) for the treatment of mCRPC patients whose metastases are limited to the bones. Radium-223 is an α-emitting alkaline earth metal ion, which, similar to calcium ions, accumulates in the bone. In a phase III study (ALSYMPCA), mCRPC patients with bone metastases received best standard-of-care treatment with placebo or (223)RaCl2. At a prespecified interim analysis, the primary endpoint of median overall survival was significantly extended by 3.6 months in patients treated with radium-223 compared with placebo (P < 0.001). The radioisotope was well tolerated and gave limited bone marrow suppression. (223)RaCl2 is the first bone-targeting antitumor therapy that received FDA approval based on a significant extended median overall survival. Further studies are required to optimize its dosing and to confirm its efficacy and safety in cancer patients.

Radium Ra 223 dichloride in castration-resistant prostate cancer.

Radium Ra 223 dichloride (Xofigo®, formerly Alpharadin) is one of the representative α-particle-emitting isotopes that delivers radiation with a higher biological effect to a more localized area. Preclinical studies in mouse, rat and canine models have demonstrated that radium Ra 223 dichloride has a definite skeletal affinity and antitumor effect with a relatively low toxicity on bone marrow. More recently, in a large randomized phase III trial (ALSYMPCA), patients with bone metastasis and castration-resistant prostate cancer (CRPC) received six cycles of 50 kBq/kg of radium Ra 223 dichloride in 4-week intervals. In these men, radium Ra 223 dichloride improved the median overall survival by 3.6 months when compared to the placebo group. Collectively, these results suggest that radium Ra 223 dichloride is a promising candidate for managing bone metastases in patients with CRPC.

Ingestion dose from 238U, 232Th, 226Ra, 40K and 137Cs in cereals, pulses and drinking water to adult population in a high background radiation area, Odisha, India.

A natural high background radiation area is located in Chhatrapur, Odisha in the eastern part of India. The inhabitants of this area are exposed to external radiation levels higher than the global average background values, due to the presence of uranium, thorium and its decay products in the monazite sands bearing placer deposits in its beaches. The concentrations of (232)Th, (238)U, (226)Ra, (40)K and (137)Cs were determined in cereals (rice and wheat), pulses and drinking water consumed by the population residing around this region and the corresponding annual ingestion dose was calculated. The annual ingestion doses from cereals, pulses and drinking water varied in the range of 109.4-936.8, 10.2-307.5 and 0.5-2.8 µSv y(-1), respectively. The estimated total annual average effective dose due to the ingestion of these radionuclides in cereals, pulses and drinking water was 530 µSv y(-1). The ingestion dose from cereals was the highest mainly due to a high consumption rate. The highest contribution of dose was found to be from (226)Ra for cereals and drinking water and (40)K was the major dose contributor from the intake of pulses. The contribution of man-made radionuclide (137)Cs to the total dose was found to be minimum. (226)Ra was found to be the largest contributor to ingestion dose from all sources.

Preparation and biodistribution of 188Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs) in vivo.

BACKGROUND: The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide (188)Re-labeled folic acid ligand ((188)Re-folate-CDDP/HSA). METHODS: Human serum albumin was labeled with (188)Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g) was measured in vital organs. The biodistribution of (188)Re-folate-CDDP/HAS magnetic nanoparticles was assessed. RESULTS: Optimal conditions for (188)Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L), 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL), 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L), 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and (188)ReO(4) eluent (0.1 mL). The rate of (188)Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the (188)Re-folate-CDDP/HSA magnetic nanoparticles were injected into nude mice. Uptake of (188)Re-folate-CDDP/HSA magnetic nanoparticles increased gradually after injection, peaked at 8 hours with a value of 8.83 ± 1.71, and slowly decreased over 24 hours in vivo. CONCLUSION: These results indicate that (188)Re-folate-CDDP/HSA magnetic nanoparticles can be used in radionuclide-targeted cancer therapy. Surface-modified albumin nanoparticles with folic acid ligand-labeled radionuclide ((188)Re) were successfully prepared, laying the foundation for a triple-killing effect of thermotherapy, chemotherapy, and radiation therapy.

Imaging of the striatal and extrastriatal dopamine transporter with (18)F-LBT-999: quantification, biodistribution, and radiation dosimetry in nonhuman primates.

UNLABELLED: The aim of this study was to evaluate the quantification, biodistribution, and radiation dosimetry of the novel dopamine transporter (DAT) radioligand (18)F-(2S,3S)-methyl 8-((E)-4-fluorobut-2-en-1-yl)-3-(p-tolyl)-8-azabicyclo[3.2.1]octane-2-carboxylate ((18)F-LBT-999) in nonhuman primates. METHODS: The brain study was conducted in 4 female rhesus monkeys. PET measurements were conducted for 243 min using the high-resolution research tomograph (HRRT) with the measurement of the metabolite-corrected arterial input function and protein binding. Quantification was performed with kinetic analysis using 2-tissue- and 1-tissue-compartment models, with Logan graphical analysis and with different reference tissue models. The outcome measures were total distribution volume (V(T)), nondisplaceable distribution volume (V(ND)), binding potential relative to the free concentration of radioligand in plasma (BP(F)), and binding potential relative to the concentration of nondisplaceable radioligand in tissue (BP(ND)) = V(T) - V(ND)/V(ND) using the cerebellum as a reference region. For the biodistribution and radiation dosimetry, 2 female cynomolgus monkeys were studied. Whole-body PET scans were obtained using a PET/CT system for approximately 250 min. Estimates of the absorbed radiation dose in humans were calculated using OLINDA/EXM software. RESULTS: (18)F-LBT-999 showed good brain uptake (300% standardized uptake value) and regional distribution according to known DAT density. The 2-tissue-compartment model was the preferred model for the quantification. Late peak equilibrium (120-140 min) and slow washout were observed in the striatum, with high variability of V(T), BP(F), and BP(ND). When the different models were compared with the 2-tissue-compartment model, the underestimation of V(T) or BP(ND) was larger in the caudate and putamen than in the midbrain and thalamus. The reference tissue models were suitable for the quantification. The whole-body distribution study showed that the main routes of excretion of (18)F-LBT-999 were the urinary and gastrointestinal systems, with the bladder being the critical organ. Accumulation of (18)F-LBT-999 was found in the bone and skull, with a relatively high dose estimated for the osteogenic cells. The range of calculated effective dose was 0.021-0.022 mSv/MBq. CONCLUSION: (18)F-LBT-999 seemed to be a suitable PET radioligand for the DAT quantification, particularly for extrastriatal regions. The skull uptake did not seem to be a limitation for brain imaging. The calculated dosimetry estimates based on data in nonhuman primates seemed comparable with those of other clinically used (18)F-labeled radioligands, for example, (18)F-FDG (0.024-0.027 mSv/MBq).

Radiological impacts of phosphogypsum.

This study was carried out to assess the radiological impact of Syrian phosphogypsum (PG) piles in the compartments of the surrounding ecosystem. Estimating the distribution of naturally occurring radionuclides (i.e. (226)Ra, (238)U, (232)Th, (210)Po and (210)Pb) in the raw materials, product and by-product of the Syrian phosphate fertilizer industry was essential. The data revealed that the concentrations of the radionuclides were enhanced in the treated phosphate ore. In PG, (226)Ra content had a mean activity of 318 Bq kg(-1). The uranium content in PG was low, ca. 33 Bq kg(-1), because uranium remained in the phosphoric acid produced. Over 80% of (232)Th, (210)Po and (210)Pb present partitioned in PG. The presence of PG piles did not increase significantly the concentration of (222)Rn or gamma rays exposure dose in the area studied. The annual effective dose was only 0.082 mSv y(-1). The geometric mean of total suspended air particulates (TSP) ca. 85 µg m(-3). The activity concentration of the radionuclides in filtrates and runoff waters were below the detection limits (ca. 0.15 mBq L(-1) for (238)U, 0.1 mBq L(-1) for (232)Th and 0.18 mBq L(-1) for both of (210)Po and (210)Pb); the concentration of the radionuclides in ground water samples and Qattina Lake were less than the permissible limits set for drinking water by the World Health Organisation, WHO, (10, 1 and 0.1 Bq L(-1) for (238)U, (232)Th and both of (210)Po and (210)Pb, respectively). Eastern sites soil samples of PG piles recorded the highest activity concentrations, i.e. 26, 33, 28, 61 and 40 Bq kg(-1) for (226)Ra, (238)U, (232)Th, (210)Po and (210)Pb, respectively, due to the prevailing western and north-western wind in the area, but remained within the natural levels reported in Syrian soil (13-32 Bq kg(-1) for (226)Ra, 24.9-62.2 Bq kg(-1) for (238)U and 10-32 Bq kg(-1) for (232)Th). The impact of PG piles on plants varied upon the plant species. Higher concentrations of the radionuclides were recorded for grass in comparison to broad-leaved plants. Among the species that grow naturally on PG piles, Inula, Ecballium and Polygonium may be radionuclides accumulators. A determined effort is needed at a national level to achieve a common and coherent approach to regulate PG piles or to consider it a resource material rather than waste or residue.

Adaptation and impairment of DNA repair function in pollen of Betula verrucosa and seeds of Oenothera biennis from differently radionuclide-contaminated sites of Chernobyl.

BACKGROUND AND AIMS: The plants that have remained in the contaminated areas around Chernobyl since 1986 encapsulate the effects of radiation. Such plants are chronically exposed to radionuclides that they have accumulated internally as well as to alpha-, beta- and gamma-emitting radionuclides from external sources and from the soil. This radiation leads to genetic damage that can be countered by DNA repair systems. The objective of this study is to follow DNA repair and adaptation in haploid cells (birch pollen) and diploid cells (seed embryos of the evening primrose) from plants that have been growing in situ in different radionuclide fall-out sites in monitored regions surrounding the Chernobyl explosion of 1986. METHODS: Radionuclide levels in soil were detected using gamma-spectroscopy and radiochemistry. DNA repair assays included measurement of unscheduled DNA synthesis, electrophoretic determination of single-strand DNA breaks and image analysis of rDNA repeats after repair intervals. Nucleosome levels were established using an ELISA kit. KEY RESULTS: Birch pollen collected in 1987 failed to perform unscheduled DNA synthesis, but pollen at gamma/beta-emitter sites has now recovered this ability. At a site with high levels of combined alpha- and gamma/beta-emitters, pollen still exhibits hidden damage, as shown by reduced unscheduled DNA synthesis and failure to repair lesions in rDNA repeats properly. Evening primrose seed embryos generated on plants at the same gamma/beta-emitter sites now show an improved DNA repair capacity and ability to germinate under abiotic stresses (salinity and accelerated ageing). Again those from combined alpha- and gamma/beta-contaminated site do not show this improvement. CONCLUSIONS: Chronic irradiation at gamma/beta-emitter sites has provided opportunities for plant cells (both pollen and embryo cells) to adapt to ionizing irradiation and other environmental stresses. This may be explained by facilitation of DNA repair function.

An experimental palladium-103 seed (OptiSeedexp) in a biocompatible polymer without a gold marker: characterization of dosimetric parameters including the interseed effect.

Permanent implantation of 125I (iodine) or 103Pd (palladium) sources is a popular treatment option in the management of early stage prostate cancer. New sources are being developed, some of which are being marketed for different clinical applications. A new technique of adjuvant stereotactic permanent seed breast implant, similar to that used in the treatment of prostate cancer, has been proposed by [N. Jansen et al., Int. J. Radiat. Oncol. Biol. Phys. 67, 1052-1058 (2007)] with encouraging results. The presence of artifacts from the metallic seeds, however, can disturb follow-up imaging. The development of plastic seeds has reduced these artifacts. This paper presents a feasibility study of the advantages of palladium-103 seeds, encapsulated with a biocompatible polymer, for future clinical applications, and on the effect of the gold marker on the dosimetric characteristics of such seeds. Experimental palladium seeds, OptiSeedexp, were manufactured by International Brachytherapy (IBt), Seneffe, Belgium, from a biocompatible polymer, including the marker. Apart from the absence of a gold marker, the studied seed has an identical design to the OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)]. Polymer encapsulation was preferred by IBt in order to reduce the quantity of radioactive material needed for a given dose rate and to reduce the anisotropy of the radiation field around the seed. In addition, this design is intended to decrease the interseed effects that can occur as a result of the marker and the encapsulation. Dosimetric measurements were performed using LiF thermoluminescent dosimeters (1 mm3) in solid water phantoms (WT1). Measured data were compared to Monte Carlo simulated data in solid water using the MCNP code, version 4C. Updated cross sections [Med. Phys. 30, 701-711 (2003)] were used. As the measured and calculated data were in agreement, Monte Carlo calculations were then performed in liquid water to obtain relevant dosimetric data as required by TG-43U1 recommendations. Comparison of the results with previous studies of OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)], and of InterSource103 [Appl. Radiat. Isot. 57, 805-811 (2002)] showed very good agreement for the dose rate constant and for the radial dose function. With respect to the anisotropy function, the relative dose (anisotropy value relative to 90 degrees) from the polymer seed at a distance of 3 cm was close to unity (105%) at 0 degrees, whereas the relative values for the OptiSeed103 with a gold marker and the titanium-encapsulated InterSource103 seed decreased to 70% and 40%, respectively. The interseed effect from one seed was negligible and in the order of calculation uncertainty, making calculation of the dose rate distribution of the studied seeds, according to TG43U1 recommendations, more accurate and closer to reality. This feasibility study shows that due to the low energy of palladium-103, the negligible interseed effect and the reduced artifacts in postimplant medical imaging, this experimental plastic seed would be a good source for breast brachytherapy. This feasibility study was carried out in collaboration with IBt and will be continued with a study of its visibility in different tissues.

How iliopelvic lymphoscintigraphy can affect the definition of planning target volume in radiation therapy of pelvic and testicular tumors.

PURPOSE: External beam radiation therapy (EBRT) of most intrapelvic and testicular tumors has been generally performed with large fields encompassing both the primary disease and lymphatic drainage. This study was carried out to map the pelvic and periaortic lymphatics by means of iliopelvic lymphoscintigraphy (IPL) in preparation for radiotherapy planning. METHODS AND MATERIALS: Between January 2000 and October 2001, 70 patients scheduled for EBRT (61 operated on, 52 females, 18 males, mean age 61, range, 24-80), affected with uterine (43), rectal (11), testicular (8), anal (4), penile (2), and vulvar (2) cancers were enrolled in the study. IPL was performed by injection of 99mtechnetium-nanocolloids in the bipedal (70 cases) or bipedal plus perianal (20 cases) sites. The sensitivity of IPL in mapping the lymphatic anatomy was evaluated first. Then three radiation oncologists scored the modifications induced by IPL on the planning target volume (PTV) which had been previously delineated only on the basis of bony landmarks. The original fields were classified "inadequate" if they failed to match the new PTV by more than 1 cm. RESULTS: IPL sensitivity in showing the inguinal, external iliac, common, and periaortic lymphatics was 100%, 90%, 80%, and 70% in anterior-posterior (A-P) projections, and 100%, 80%, 70%, and 60% in lateral projections respectively. For the presacral and hypogastric ones the sensitivity was 40%. When compared with bony landmarks, IPL changed the delineation of PTV in 24 of 70 A-P P-A fields (34%) and 22 of 58 (38%) lateral fields. Furthermore, 8/12 (67%) lymphadenectomies resulted in being incomplete. No IPL-related toxicity was observed. CONCLUSION: IPL is a safe, inexpensive (cost: 100 Euros), and effective method to map the lymphatic chains. In the A-P scintigrams these structures were detected in 85% (70-100%) of the patients referred for total pelvis irradiation, and this figure could be higher in subjects not operated on. IPL can also give a reliable evaluation of the lymphadenectomies in order to schedule the proper treatments after surgery. Finally, IPL may change the conventional PTV for pelvic irradiation in about 36% (34-38%) of the cases; therefore, the fields should be tailored more around the lymphatic landmarks than the bony landmarks.

X-ray image intensifier performance and patient doses for combinations of supplemental beam filters and vascular contrast agents.

We present an investigation of the fluoroscopic imaging and dosimetric performances of iodine- and gadolinium-based vascular contrast agents in combination with K-absorption edge filters of atomic numbers between 50 (tin) and 82 (lead). These combinations were studied using a theoretical model for a range of diagnostic x-ray spectra (55 to 100 kVp) and for water phantoms representative of thin and thick anatomies. Performance was characterized by radiographic contrast, a derived image quality index, the patient integral and entrance skin doses, and the x-ray tube load. For a given thickness of anatomy, an optimum combination of spectrum kVp, contrast agent and supplemental filter was defined by maximum imaging performance for a minimum or tolerable x-ray tube load and patient dose. It was possible to both improve imaging performance and reduce dose by the use of an appropriate combination of spectrum kVp and filter. For gadolinium-based contrast, performance was optimized with tungsten filtration at 90 kVp for both thin and thick anatomies. It was not possible, however, to optimize the iodinated contrast performance with a single combination of supplemental filter and spectrum kVp. The optimal performance for iodinated contrast was achieved with gadolinium filtration at 60 kVp for thin anatomy and with ytterbium filtration at 80 kVp for thick anatomy. The best performance for thin anatomy was that of the combination of iodinated contrast/gadolinium filter at 60 kVp and the best performance for thick anatomy was that of the combination of gadolinium-based contrast/tungsten filter at 90 kVp.