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A Melillo

Publications and source records attributed to A Melillo.

5 recordsLinked to original sources

Aspirin blocks binding of photosensitizer SnET2 into human serum albumin: implications for photodynamic therapy.

Tin etiopurpurin dichloride (SnET2) is one of the photosensitizers under investigation to be used in photodynamic therapy of prostate cancer. The drug is delivered intravenously, transported in vivo by liposomes and plasma proteins and localized within the prostate. SnET2 exists in two tautomeric forms (I - closed ring, II - open ring) with I converting spontaneously into the more energetically stable form II at physiological pH. Up to approximately 50% of the drug can be carried by serum albumin, although this association can increase photo-bleaching and diminish the drug efficiency. Molecular modeling and force field calculations indicate that Sudlow Site I in human serum albumin (HSA) is the most probable binding site for both forms of SnET2, with the porphyrin moiety nestling between domains IIA and IB, and the esterolytic side group oriented toward domain IIIA of HSA. Other drugs, including aspirin, bind to the same part of HSA. SnET2 does not bind to HSA when pre-incubated with aspirin, which confirms that its place of binding to this protein must be located near Lys199. This observation could be exploited to improve photo-efficiency of SnET2 by finding drugs that could compete with the photosensitizer for binding into Sudlow Site I of HSA.

Aspirin↗

Some treatment planning considerations for 103Pd and 125I permanent interstitial implants.

Sealed sources of palladium-103 (103Pd), which decay with a half life of 17 days and emit on average 21 keV photons, are now in clinical use for permanent implants. For seed implantation of prostatic cancer, 103Pd implants are usually planned to deliver 115 Gy to full decay at an initial dose rate of 19.7 cGy/hr whereas 125I implants are usually planned to deliver 160 Gy at an initial dose rate of 7.72 cGy/hr. Because of the lower energy of photons emitted by 103Pd compared to the 125I sources (27 keV average energy), the tissue attenuation is more severe for 103Pd sources. The radial dose function drops more steeply with distance from the 103Pd sources compared to the 125I sources, raising a concern about the possibility of cold spots in the tumors implanted with 103Pd sources. To investigate this issue, a detailed analysis of the dependence of dose uniformity as a function of seed spacing for 125I and 103Pd sources in various cubic and spherical configurations was carried out. Using the measured single source dosimetry data as input, dose distributions for a variety of cubic and spherical implants were generated on a computerized treatment planning system. This study indicates that relative dose distributions for 125I and 103Pd implants with the same geometric configuration and number of seeds are very similar inside the implanted volume for implants. Dose uniformity within a target volume implanted with 103Pd seeds is also very similar to that for 125I. To expedite clinical implementation of 103Pd, an atlas of dose distributions for 103Pd implants has been produced for various seed configurations, seed spacings, and target volumes. Using 125I implants as a guideline, clinical procedures for planning of 103Pd implants have been developed. It was found that the total source strength implanted divided by the dimension of the implant can be expressed as an exponential function of implant size, resulting in a simple method for estimating the strength of seeds necessary in an implant. Also, the air kerma strength of 103Pd seeds is about 3.3 times that of 125I sources in an implant with the same geometric configuration and number of seeds, provided treatment doses of 115 Gy and 160 Gy are chosen for 103Pd and 125I implants, respectively.

Brachytherapy↗

Anisotropy functions for 103Pd, 125I, and 192Ir interstitial brachytherapy sources.

Anisotropy of dose distributions around 103Pd, 125I, and 192Ir sources for interstitial brachytherapy was examined. Dose rates around 125I models 6702 and 6711 and 192Ir sources were measured using lithium fluoride thermoluminescence dosimeters (LiF TLDs) in a water-equivalent, solid phantom. From these measured data for 125I and 192Ir and the previously published measured data for 103Pd, isodose rate contours were determined using a bivariate interpolation and smooth surface fitting algorithm. The anisotropy functions, F(r,theta), as defined by the Interstitial Collaborative Working Group (ICWG) for each source, were determined. Also, 4 pi-averaged anisotropy factors, phi an(r), for use in point source approximation, have been calculated at radial distances varying from 1-10 cm for 103Pd, 125I, and 192Ir sources. The anisotropy factors had average values of 0.90, 0.93, 0.95, and 0.98 for 103Pd, 125I model 6711, 125I model 6702, and 192Ir, respectively. The anisotropy factors determined from dose measurements in phantom are observed to be closer to unity than from those determined previously from in-air measurements. This can be attributed to the smoothing of two-dimensional dose distributions due to the presence of more scattered photons in the phantom measurements compared to in-air measurements. Because in-phantom measurements simulate more closely the brachytherapy patient, data from these experiments are recommended for a more accurate determination of dose distributions around clinical brachytherapy implants. In this work, we present a complete set of source data for two-dimensional dosimetry following the ICWG formalism.

Anisotropy↗

Dosimetric characteristics of a double wall 125I source for interstitial brachytherapy.

Recently, a newly designed encapsulated source of 125I has become commercially available for use in permanent and temporary interstitial brachytherapy. The 125I sources in current use come in two different configurations: the Model 6711 source (Medi Physics/Amersham) for permanent implants has radioactive iodine adsorbed on the surface of a silver wire, and the Model 6702 (Medi Physics/Amersham) source for temporary implants has radioactive iodine absorbed in three spherical resin balls. Both of these iodine sources are encapsulated in a thin-walled shell (0.05-mm thick) made of titanium. The newly designed 125I source (Best Industries Model 2300 series) contains radioactive iodine adsorbed on a tungsten wire that is encapsulated by two walls of titanium. This double-walled 125I source offers the following potential advantages: (i) Because it contains radioactive iodine on the ends as well as the circular surface of the tungsten wire, it can produce a more isotropic dose distribution than the sources in current use; (ii) because it is available in a wider range of source strengths, it is suitable for both temporary and permanent implantation; (iii) because it has a tungsten radiographic marker, source localization is considerably easier than the 125I Model 6702 source that has no radiographic marker; and (iv) because it uses a double-walled encapsulation the risk of radioactive contamination due to source rupture is considerably reduced. In this work, dose distributions produced by the new design 125I source (Model 2300) for interstitial brachytherapy have been measured using LiF TLD's in a Solid Water phantom. Dosimetric characteristics of the new 125I sources are compared with those of the currently available 125I sources.(ABSTRACT TRUNCATED AT 250 WORDS)

Anisotropy↗