Clinical evaluations of cast gold alloy, machinable zirconia, and semiprecious alloy crowns: A multicenter study.

STATEMENT OF PROBLEM: Few studies have compared the marginal and internal fits of crowns fabricated from machinable palladium-silver-indium (Pd-Ag-In) semiprecious metal alloy. PURPOSE: The purpose of this clinical study was to evaluate and compare the marginal and internal fits of machined Pd-Ag-In alloy, zirconia, and cast gold crowns. MATERIAL AND METHODS: A prospective clinical trial was performed on 35 participants and 52 abutment teeth at 2 centers. Individuals requiring prosthetic restorations were treated with gold alloy or zirconia crowns (2 control groups) or Pd-Ag-In alloy crowns (experimental group). A replica technique was used to evaluate the marginal and internal fits. The buccolingual and mesiodistal cross-sections were measured, and a noninferiority comparison was conducted. RESULTS: The mean marginal gaps were 68.2 µm for the gold crowns, 75.4 µm for the zirconia crowns, and 76.9 µm for the Pd-Ag-In alloy crowns. In the 5 cross-sections other than the distal cross-section, the 2-sided 95% confidence limits for the differences between the Pd-Ag-In alloy crowns and the 2 control groups were not larger than the 25-µm noninferiority margin. The control groups displayed smaller internal gaps in the line angle and occlusal spaces compared with the Pd-Ag-In crown group. CONCLUSION: The marginal gaps of machinable Pd-Ag-In alloy crowns did not meet the noninferiority criterion in the distal margin compared with zirconia and gold alloy crowns. Nonetheless, all 3 crowns had clinically applicable precision.

Sub-10-nm Pd nanosheets with renal clearance for efficient near-infrared photothermal cancer therapy.

Efficient renal clearance is of fundamentally important property of nanoparticles for their in vivo biomedical applications. In this work, we report the successful synthesis of ultra-small Pd nanosheets (SPNS) with an average diameter of 4.4 nm and their application in photothermal cancer therapy using a near infrared laser. The ultra-small Pd nanosheets have strong optical absorption in the NIR region and high photothermal conversion efficiency (52.0%) at 808 nm. After being surface-functionalized with reduced glutathione (GSH), the SPNS-GSH was administered to mice to investigate the biodistribution, photothermal efficacy and tumor ablation in vivo. The in vivo photothermal therapy studies clearly demonstrate that surface modification with GSH allows the nanosheets to exhibit prolonged blood circulation and thus high accumulation in tumors. Upon 808 nm NIR irradiation, the tumors can be completely ablated. More importantly, with the size below the renal filtration limit (<10 nm), the GSHylated Pd nanosheets can be nicely cleared from body through the renal excretion route and into urine. Together with the high efficacy of NIR photothermal therapy, the unique renal clearance properties make the ultra-small Pd nanosheets promising for practical use in photothermal cancer therapy.

1T-Phase Dirac Semimetal PdTe2 Nanoparticles for Efficient Photothermal Therapy in the NIR-II Biowindow.

1T-phase transition-metal dichalcogenides (TMDs) nanomaterials are one type of emerging and promising near-infrared II (NIR-II) photothermal agents (PTAs) derived from their distinct metallic electronic structure, but it is still challenging to synthesize these nanomaterials. Herein, PdTe2 nanoparticles (PTNs) with a 1T crystal symmetry and around 50 nm in size are prepared by an electrochemical exfoliation method, and the corresponding photothermal performances irradiated under a NIR-II laser have been explored. The encapsulation of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) endows PTNs with water solubility, enhanced photothermal stability, and high biocompatibility. Notably, PTN/DSPE-PEG displays a potent absorbance through the NIR-II zone and considerable photothermal conversion efficiency, which is up to 68% when irradiated with a 1060 nm laser. With these unique photothermal properties, excellent in vitro and in vivo tumor inhibition effects of PTN/DSPE-PEG have been achieved under the irradiation of a NIR-II (1060 nm) laser without visible toxicity to normal tissues, suggesting that it is an efficient NIR-II photothermal nanoagent.

A comparison of the shielding effectiveness of silicone oil vitreous substitutes when used with Palladium-103 and Iodine-125 eye plaques.

PURPOSE: Episcleral eye plaques provide excellent local control of ocular melanoma, but vision sparing remains a significant problem with 30% or more of patients experiencing significant visual acuity degradation. The use of silicone oil shielding with Iodine-125 plaques has previously been reported to improve critical structure sparing. We hypothesized that the use of Palladium-103 would improve the shielding effectiveness of silicone oil due to the strong energy dependence of the photoelectric effect. This Monte Carlo simulation study reports a comparison of the shielding effects of silicone oil when used in conjunction with Pd-103 and with I-125 plaques. MATERIALS AND METHODS: GEANT4 was used to simulate eye plaque treatments to an eye with either water-equivalent vitreous humor, or silicone oil in place of the vitreous humor. Two solid gold plaques, 15 and 23 mm, were simulated loaded with I-125 and with Pd-103 source seeds. Seed activity was normalized such that 85 Gy was delivered to the tumor apex in the water-equivalent cases. Tumor apex dose, central axis dose, and inner sclera dose reductions with silicone oil were evaluated. RESULTS: Silicone oil resulted in an underdosing to the tumor apex of 6.1% and 7.5% in the 15 mm plaque for I-125 and Pd-103, respectively, and 3.4% and 4.3% in the 23 mm plaque for I-125 and Pd-103, respectively. When renormalized to 85 Gy to the tumor apex in all scenarios, silicone oil reduced the dose to the inner sclera 90° from the plaque by 19-32% for the 15 and 23 mm plaques using I-125, and by 33-65% for the 15 and 23 mm plaques using Pd-103. CONCLUSIONS: The combination of silicone oil and Pd-103 eye plaques offers the potential for greatly improved sparing to normal structures compared to Pd-103 plaques alone or I-125 plaques with or without silicone oil.

Monte Carlo dosimetry for 125I and 103Pd eye plaque brachytherapy.

A Monte Carlo study of dosimetry for eye plaque brachytherapy is performed. BrachyDose, an EGSnrc user code which makes use of Yegin's multi-geometry package, is used to fully model 125I (model 6711) and 103Pd (model 200) brachytherapy seeds and the standardized plaques of the Collaborative Ocular Melanoma Study (COMS). Three-dimensional dose distributions in the eye region are obtained. In general, dose to water is scored; however, the implications of replacing water with eye tissues are explored. The effect of the gold alloy (Modulay) backing is investigated and the dose is found to be sensitive to the elemental composition of the backing. The presence of the silicone polymer (Silastic) seed carrier results in substantial dose decreases relative to water, particularly for 103Pd. For a 20 mm plaque with a Modulay backing and Silastic insert, fully loaded with 24 seeds, the dose decrease relative to water is of the order of 14% for 125I and 20% for 103Pd at a distance of 1 cm from the inner sclera along the plaque's central axis. For the configurations of seeds used in COMS plaques, interseed attenuation is a small effect within the eye region. The introduction of an air interface results in a dose reduction in its vicinity which depends on the plaque's position within the eye and the radionuclide. Introducing bone in the eye's vicinity also causes dose reductions. The dose distributions in the eye for the two different radionuclides are compared and, for the same prescription dose, 103Pd generally offers a lower dose to critical normal structures. BrachyDose is sufficiently fast to allow full Monte Carlo dose calculations for routine clinical treatment planning.

Photon energy spectrum emitted by a novel polymer-encapsulated 103Pd source and its effect on the dose rate constant.

Two independent groups have published intrinsic dosimetry parameters for the recently introduced OptiSeed103 interstitial brachytherapy source which contains 103Pd encapsulated by a novel polymer shell. The dose rate constant (Lambda) reported by the two groups, however, differed by more than 6% and there is currently no AAPM recommended consensus value for this source in clinical dosimetry. The aim of this work was to perform an independent determination of Lambda for the OptiSeed103 source using a recently developed photon spectrometry technique. Three OptiSeed103 sources (model 1032P) with known air-kerma strength were used in this study. The photon energy spectrum emitted along the radial direction on the source's bisector was measured in air using a high-resolution intrinsic germanium spectrometer designed and established for low-energy brachytherapy source spectrometry. The dose rate constant of each source was determined from its emitted energy spectrum and the spatial distribution of radioactivity in the source. Unlike other sources made with traditional titanium encapsulation, the photons emitted by the OptiSeed103 sources exhibited only slight spectral hardening, yielding a relative energy spectrum closer to that emitted by bare 103Pd. The dose rate constant determined by the photon spectrometry technique for water was 0.664 +/- 0.025 cGy h(-1) U(-1). This value agreed, within experimental uncertainties, with the Monte Carlo-calculated value (MCLambda) of 0.665 +/- 0.014 cGy h(-1) U(-1) and the TLD-measured value (with a Monte Carlo-calculated solid-phantom-to-water conversion factor) of 0.675 +/- 0.051 cGy h(-1) U(-1) reported by Wang and Hertel [Appl. Radiat. Isot. 63, 311-321 (2005)]. However, it differed by -6.7% from the McLambda of 0.712 +/- 0.043 cGy h(-1) U(-1) reported by Bernard and Vynckier [Phys. Med. Biol. 50, 1493-1504 (2005)]. The results obtained in this work provide additional information needed for establishing a consensus value for the dose rate constant for the OptiSeed103 source. It suggests that an eventual consensus value of Lambda for the OptiSeed103 source is likely to be closer to a value of 0.668 cGy h(-1) U(-1) rather than 0.693 cGy h(-1) U(-1) as initially recommended by the source manufacturer based on the two previously published results.

Improved treatment planning for COMS eye plaques.

PURPOSE: A recent reanalysis of the Collaborative Ocular Melanoma Study (COMS) medium tumor trial concluded that incorporating factors to account for anisotropy, line source approximation, the gold plaque, and attenuation in the Silastic seed carrier into the dose calculations resulted in a significant and consistent reduction of calculated doses to structures of interest within the eye. The authors concluded that future eye plaque dosimetry should be "performed using the most up-to-date parameters available." The reason these factors are important is attributable to the low energy (125)I radiation (approximately 28 keV) that is primarily absorbed by the photoelectric process. Photoelectric absorption is quite dependent on the atomic composition of the absorbing material. Being 40% silicon by weight, the effective atomic number of Silastic is significantly greater than that of water. Although the AAPM TG43 brachytherapy formalism inherently addresses the issues of source anisotropy and geometry, its parameter that accounts for scatter and attenuation, the radial dose function g(r), assumes that the source is immersed in infinite homogeneous water. In this work, factors are proposed for (125)I that correct for attenuation in the Silastic carrier and scatter deficits resulting from the gold plaque and nearby air. The implications of using (103)Pd seeds in COMS plaques are also discussed. METHODS AND MATERIALS: An existing TG43-based ophthalmic plaque planning system was modified to incorporate additional scatter and attenuation correction factors that better account for the path length of primary radiation in the Silastic seed carrier and the distance between the dose calculation point and the eye-air interface. RESULTS: Compared with homogeneous water, the dose-modifying effects of the Silastic and gold are greatest near the plaque surface and immediately adjacent to the plaque, while being least near the center of the eye. The calculated dose distribution surrounding a single (125)I seed centered in a COMS 20 mm plaque was found to be consistent with previously published examples that used thermoluminescent dosimetry measurements and Monte Carlo methods. For fully loaded 12 and 20 mm plaques, calculated dose to critical ocular structures ranged from 16%-50% less than would have been reported using the standard COMS dose calculation protocol. CONCLUSIONS: Treatment planning for COMS eye plaques that accurately accounts for the presence of the gold, Silastic and extraocular air is both possible and practical.

Dosimetric study of a new polymer encapsulated palladium-103 seed.

The use of low-energy photon emitters for brachytherapy applications, as in the treatment of prostate or ocular tumours, has increased significantly over the last few years. Several new seed models utilizing 103Pd and 125I have recently been introduced. Following the TG43U1 recommendations of the AAPM (American Association of Physicists in Medicine) (Rivard et al 2004 Med. Phys. 31 633), dose distributions around these low-energy photon emitters are characterized by the dose rate constant, the radial dose function and the anisotropy function in water. These functions and constants can be measured for each new seed in a solid phantom (i.e. solid water such as WT1) using high spatial resolution detectors such as very small thermoluminescent detectors. These experimental results in solid water must then be converted into liquid water by using Monte Carlo simulations. This paper presents the dosimetric parameters of a new palladium seed, OptiSeed (produced by International Brachytherapy (IBt), Seneffe, Belgium), made with a biocompatible polymeric shell and with a design that differs from the hollow titanium encapsulated seed, InterSource103, produced by the same company. A polymer encapsulation was chosen by the company IBt in order to reduce the quantity of radioactive material needed for a given dose rate, and to improve the symmetry of the radiation field around the seed. The necessary experimental data were obtained by measurements with LiF thermoluminescent dosimeters (1 mm3) in a solid water phantom (WT1) and then converted to values in liquid water using Monte Carlo calculations (MCNP-4C). Comparison of the results with a previous study by Reniers et al (2002 Appl. Radiat. Isot. 57 805) shows very good agreement for the dose rate constant and for the radial dose function. In addition, the results also indicate an improvement in isotropy compared to a conventional titanium encapsulated seed. The relative dose (anisotropy value relative to 90 degrees ) from the seed at a distance of 3 cm is close to 70% at 0 degrees whereas that for the titanium encapsulated InterSource103seed is close to 40%. This paper also presents some new Monte Carlo calculations relating to shadowing produced by the seeds in an array implanted for a prostate cancer treatment. Recently, Mobit and Badragan (2004 Phys. Med. Biol. 49 3171) reported shadowing resulting in a 10% decrease in dose from titanium encapsulated 125I seed. We used Monte Carlo simulations (MCNP-4C) to evaluate shadowing for the InterSource103 titanium encapsulated seed and the OptiSeed polymer encapsulated seed. For a specific geometry specified, dose decreases of 13% and 7% were found for the InterSource103 titanium encapsulated and the OptiSeed polymer encapsulated seed, respectively.

Air-kerma strength determination of a new directional (103)Pd source.

PURPOSE: A new directional (103)Pd planar source array called a CivaSheet™ has been developed by CivaTech Oncology, Inc., for potential use in low-dose-rate (LDR) brachytherapy treatments. The array consists of multiple individual polymer capsules called CivaDots, containing (103)Pd and a gold shield that attenuates the radiation on one side, thus defining a hot and cold side. This novel source requires new methods to establish a source strength metric. The presence of gold material in such close proximity to the active (103)Pd region causes the source spectrum to be significantly different than the energy spectra of seeds normally used in LDR brachytherapy treatments. In this investigation, the authors perform air-kerma strength (S(K)) measurements, develop new correction factors for these measurements based on an experimentally verified energy spectrum, and test the robustness of transferring S(K) to a well-type ionization chamber. METHODS: S(K) measurements were performed with the variable-aperture free-air chamber (VAFAC) at the University of Wisconsin Medical Radiation Research Center. Subsequent measurements were then performed in a well-type ionization chamber. To realize the quantity S(K) from a directional source with gold material present, new methods and correction factors were considered. Updated correction factors were calculated using the MCNP 6 Monte Carlo code in order to determine S(K) with the presence of gold fluorescent energy lines. In addition to S(K) measurements, a low-energy high-purity germanium (HPGe) detector was used to experimentally verify the calculated spectrum, a sodium iodide (NaI) scintillating counter was used to verify the azimuthal and polar anisotropy, and a well-type ionization chamber was used to test the feasibility of disseminating S(K) values for a directional source within a cylindrically symmetric measurement volume. RESULTS: The UW VAFAC was successfully used to measure the S(K) of four CivaDots with reproducibilities within 0.3%. Monte Carlo methods were used to calculate the UW VAFAC correction factors and the calculated spectrum emitted from a CivaDot was experimentally verified with HPGe detector measurements. The well-type ionization chamber showed minimal variation in response (<1.5%) as a function of source positioning angle, indicating that an American Association of Physicists in Medicine (AAPM) Accredited Dosimetry Calibration Laboratory calibrated well chamber would be a suitable device to transfer an S(K)-based calibration to a clinical user. S(K) per well-chamber ionization current ratios were consistent among the four dots measured. Additionally, the measurements and predictions of anisotropy show uniform emission within the solid angle of the VAFAC, which demonstrates the robustness of the S(K) measurement approach. CONCLUSIONS: This characterization of a new (103)Pd directional brachytherapy source helps to establish calibration methods that could ultimately be used in the well-established AAPM Task Group 43 formalism. Monte Carlo methods accurately predict the changes in the energy spectrum caused by the fluorescent x-rays produced in the gold shield.

Two-dimensional dosimetry in the near field of the model 200 103Pd source for interstitial brachytherapy implants using a thermoluminescent sheet.

A large area and highly sensitive thermoluminescent (TL) sheet film was used for two-dimensional dose distribution measurements at millimetre distances from a 103Pd interstitial brachytherapy source. The TL film is made of Teflon homogeneously mixed with small particles of thermoluminescent material (BaSO4: Eu doped). This TL sheet (5 cm x 5 cm) was used to determine the relative dosimetric characteristics (i.e., radial dose function, 2D and 1D anisotropy functions, as defined by the updated AAPM Task Group No 43 report) of the model 200 103Pd source that emits low energy photons (21 keV). The two-dimensional dosimetry data were obtained for distances from the source surface to 15 mm. The radial dose function measured with the TL sheet is in reasonable agreement within 11% with the values recommended in the updated AAPM TG-43 report. All the measured 2D dose distributions showed limited symmetry about the source axes. The differences between the 1D anisotropy function values measured with the TL sheet and the data recommended in the updated AAPM TG-43 report were 10% at 5 mm and 7.5% at 10 mm, respectively, for the model 200 103Pd seed. Our experiments have demonstrated that it is feasible to use the TL sheet as a dosimeter in the determination of the dosimetric characteristics in the immediate vicinity of interstitial brachytherapy sources emitting low energy photons.

Use of interstitial temperature self-regulating thermal rods in the treatment of prostate cancer.

Several groups are investigating a new technique for thermal treatment of the prostate involving permanent implantation of small biocompatable rods in a procedure similar to brachytherapy. The rods are then heated by an extracorporeal alternating magnetic field. The rods are composed of an alloy of palladium and cobalt such that they are temperature self-regulating; the regulated temperature is set during manufacture. Clinically, rods with a regulating temperature in the hyperthermia range are being employed as an adjuvant to external-beam radiation. Rods with a regulation temperature in the thermal ablation range are being used in two patient groups: those with newly diagnosed stage T(1) or T(2) prostate cancer and those who have localized recurrent disease after external-beam radiation. Early data appear promising.

Quantification of the selective retention of palladium octabutoxynaphthalocyanine, a potential photothermal drug, in mouse tissues.

Palladium octabutoxynaphthalocyanine (PdNc(OBu)8) is a potential photothermal therapy (PTT) agent, absorbing strongly in the near-infrared region with no ability to induce photodynamic-type sensitisation (unlike many related napthalocyanines). We report here on the application of high pressure liquid chromatography (HPLC) with near-infrared absorption detection for the determination of the tissue accumulation and clearance of PdNc(OBu)8 in a tumour-bearing mouse model (Balb/c mice with EMT6 carcinoma tumour). Due to its insolubility in aqueous-based solvents, the drug was delivered intraperitoneally in a Cremophor-containing vehicle. Good selective accumulation of the drug into the tumour versus muscle or skin is observed, with the best combination of selectivity and tumour concentration occurring at 24-72 h after drug administration. Clearance times are quite long. Comparison with other similar drugs as reported in the literature indicates that the Cremophor-containing vehicle is likely in large part responsible for the observed pharmacokinetic behaviour. This drug shows potential for PTT and will be investigated further for therapy in this animal model.

Metal anthracycline complexes as a new class of anthracycline derivatives. Pd(II)-adriamycin and Pd(II)-daunorubicin complexes: physicochemical characteristics and antitumor activity.

Pd(II) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric absorption, fluorescence, and circular dichroism measurements, we have shown that adriamycin can form two complexes with Pd(II). The first complex (I) involves two molecules of drug per Pd(II) ion; one of the molecules is chelated to Pd(II) through the carbonyl oxygen on C12 and the phenolate oxygen on C11, and the other one is bound to Pd(II) through the nitrogen of the amino sugar. This complexation induces a stacking of the two molecules of drug. In the second complex (II), two Pd(II) ions are bound to two molecules of drug (A1 and A2). One Pd(II) is bound to the oxygen on the carbons C11 and C12 of molecule A1 and the amino sugar of molecule A2 whereas the second Pd(II) ion is bound to the oxygen on C11 and C12 of molecule A2 and the amino sugar of molecule A1. The same complexes are formed between Pd(II) and daunorubicin. The stability constant for complex II is beta = (1.3 +/- 0.5) X 10(22). Interaction with DNA has been studied, showing that almost no modification of the complex occurred. This complex displays antitumor activity against P-388 leukemia that compares with that of the free drug. Complex II, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase.