Biological effects of brachytherapy using a (32)P-patch on the skin of Sencar mice.

In recent years, specially designed patches containing beta emitters have been developed for contact brachytherapy of skin lesions. The aim of the present work was to evaluate the biological effects of the (32)P-patch on the skin of Sencar mice as a result of a brachytherapy treatment. For this purpose, a (32)P-patch was prepared with Chromic (32)P-phosphate and silicone and the classical model of two-stage skin carcinogenesis was reproduced in Sencar mice. Animals were divided in six groups. Four groups received the contact brachytherapy treatments using a scheme of a single session of 40 and 60Gy (SD40 and SD60) and a scheme of two sessions of 40 and 60Gy each (FD40 and FD60). The other two groups were used as controls of the single (CSD) and the fractionated (CFD) treatments. Radiation doses were estimated with equations derived from the MIRD DOSE scheme, and biologically effective doses (BED) were calculated according to equations derived from the linear-quadratic model. The endpoint to evaluate the treatments effects was tumor size after a follow-up period of 44 days. Finally, animals were sacrificed in order to get samples of all tumors for histological analysis and PCNA staining. Erythema, dermatitis and skin ulceration developed in almost all treated animals, but they gradually healed with regeneration of tissue during the follow-up period. Radiation effects on the skin of SD40, SD60, FD40 and FD60 showed a significant reduction of the tumor size with regard to controls, independently of the scheme and the radiation dose considered. PCNA staining scores of control groups were higher than for treated groups, independently of the scheme and the radiation dose considered. This radioactive (32)P-silicone-patch which is easy to prepare and use in the treatment of skin diseases, seems promising as a radioactive device for clinical use.

Design and bioevaluation of a 32P-patch for brachytherapy of skin diseases.

The purpose of this study was to design and evaluate a 32P patch for brachytherapy of skin diseases. We employed Phosphoric-32P-acid and Chromic 32P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected 32P patch were performed. The 32P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the 32P-silicone-patch is easy to prepare and use in the treatment of skin diseases.

32P-patch contact brachyradiotherapy in the management of recalcitrant keloids and hypertrophic scars.

Keloids are the result of excessive fibroblast proliferation and then over-abundant collagen deposition. There is no method able to guarantee absolute success in the therapeutic approach to keloids. Our case report involves a female patient with six lesions treated with a 32P-patch brachyradiotherapy. Pre-treatment and adjuvant treatment of the lesions were performed with thiomucase, 5-fluoruracil, procaine and triamcinolone. Taking into account the activity contained in each of the patches and the total radiation dose to be administered according to clinical practice, dosimetric calculations were done for each lesion. Separate silicone patches with chromic [32P]phosphate were designed for each lesion based on these calculations. Total remission was achieved in three treated lesions. The other lesions did not achieve total remission yet, but their sizes are diminishing. The differences observed in treatment outcome may be related with lesion features, adjuvant treatments and/or treatment schedule.

Evaluation of different formulations to label exogenous natural surfactant labeled with (99m-Tc-ENS): stability and toxicity studies

El surfactante natural exógeno (ENS) marcado con 99mTc (99mTc-ENS) es un nuevo agente ventilatorio para la centellografía aérea pulmonar. Con el fin de elegir una formulación estable de ENS para ser marcado rutinariamente con 99mTc en Centros de Medicina Nuclear, las propiedades de dos formulaciones (ENS + cloruro estannoso + ácido gentísico y ENS + cloruro estannoso + ácido ascórbico) y una formulación control liofiolizada del ENS fueron analizadas mensualmente por un período de 12 meses. Sus propiedades fisicoquímicas, sus porcentajes de marcación y sus distribuciones biológicas fueron adecuadas durante este período. La formulación ENS + cloruro estannoso + ácido gentísico presenta la menor dispersión en los resultados de biodistribución, por lo cual esta formulación fue elegida para la futura producción de 99mTc-ENS. El estudio de toxicidad aguda de esta última formulación demostró que la dosis tóxica es al menos 1000 veces mayor que la dosis diagnóstica

The anterior lens capsule used as support material in RPE cell-transplantation.

PURPOSE: To investigate the use of an ocular basement membrane as support material for transplanted porcine RPE cells. METHODS: Porcine RPE cells were grown on bovine corneal extracellular matrix (ECM), isolated bovine- and porcine lens capsules, and tissue culture plastic. Cell density, and cell morphology were studied by phase contrast microscopy and transmission electron microscopy. RESULTS: RPE cells grown on porcine anterior lens capsule and on ECM obtained better morphology and higher final cell density than cells grown on plastic and on bovine anterior lens capsule. It was possible to transplant the porcine anterior lens capsule to the subretinal space in pigs. Within two weeks of observation, the lens capsule was well tolerated in the subretinal space. CONCLUSION: The anterior lens capsule seems to be promising as support material for use in RPE cell-transplantation.

99mTc-ENS ventilation scintigraphy: preliminary study in human volunteers.

Exogenous natural surfactant (ENS) labeled with (99m)Tc ((99m)Tc-ENS, 900-1110 MBq), a new radiopharmaceutical for ventilation scintigraphy, was nebulized during 3 min to five volunteers. For comparative purposes, (99m)Tc-diethylenetriamine pentaacetic acid (DTPA) was studied in the same way. (99m)Tc-ENS images were of at least the same quality as (99m)Tc-DTPA images. However, in smoking volunteers, the (99m)Tc-DTPA images show some areas that seemed to be not well-ventilated, although these areas appeared well-ventilated when the study was performed with (99m)Tc-ENS. These results suggest that (99m)Tc-ENS can be used for ventilation scintigraphy to allow the observation of some areas that cannot been visualized using (99m)Tc-DTPA as ventilation agent.

A replication study of obsessional followers and offenders with mental disorders.

The purpose of this study was to compare certain demographic, clinical, and criminal variables within subgroups of obsessional followers, and compare them to a group of offenders with mental disorders to attempt to replicate earlier findings. A static group archival design utilized a non-random group of convenience and a randomly selected comparison group. Sixty-five obsessional followers and 65 offenders with mental disorders were evaluated by psychiatrists and psychologists for court ordered reasons during their criminal proceedings. Both groups were evaluated during the same period, in the same court diagnostic clinic, and generally for sentencing determinations. The obsessional followers were measured on demographic, diagnostic, pursuit, victim, threat, violence, emotional, motivational, and defense variables. Inferential comparisons that used parametric and nonparametric statistics were done within and between groups on select variables. The obsessional followers had significantly greater estimated IQ than the offenders with mental disorders, but were neither older nor better educated. There were no significant differences in the high prevalence of both DSM-IV Axis I and II diagnoses. Obsessional followers who stalked prior sexual intimates were significantly more likely to have a substance abuse or dependence diagnosis. Obsessional followers who stalked strangers or acquaintances were more likely to be delusional. The majority of the obsessional followers, primarily motivated by anger, both threatened and were violent toward person or property. The modal obsessional follower is an average or above IQ, unemployed, unmarried male in his fourth decade of life. chronically pursuing a prior sexually intimate female. He is diagnosed with substance abuse or dependence and a personality disorder NOS, and has a prior psychiatric, criminal and substance abuse history. He is angry, likely to threaten her, and assault her person or property without causing serious injury.

99mTc-ENS: a new radiopharmaceutical for aerosol lung scintigraphy. Comparison between different freeze-dried formulations.

UNLABELLED: Exogenous natural surfactant (ENS) labeled with 99mTc(99mTc-ENS) is a new radiopharmaceutical for pulmonary aerosol scintigraphy. In this study, different freeze-dried formulations were evaluated to develop a suitable and long-storage method for the ENS, the nonradioactive precursor of this radiopharmaceutical. METHODS: Two freeze-dried formulations were evaluated: the sterile ENS suspension-stannous chloride altogether lyophilized (chlorlioENS) and the lyophilized sterile ENS suspension with the addition of stannous chloride as a solid drug (lioENS). These precursors were stored at room temperature for 3 mo and then labeled with 99mTc. For comparative purposes, the sterile ENS suspension with the addition of stannous chloride labeled with 99mTc(99mTc-chlorENS) was also studied. The quality controls for each radiopharmaceutical were performed by an ascending paper chromatography to determine the labeling yield percentages. The study was performed in 30 female Sprague Dawley rats, which inhaled each radiopharmaceutical by nebulization. Twenty-five minutes after the aerosol inhalation, the animals were killed to extract their organs and measure their activity in a gamma spectrometer. The data are given as the percentage of activity concentration (C%) for each organ. RESULTS: The physicochemical properties of lioENS were adequate for a freeze-dried product. The labeling yields for 99mTc-lioENS and for 99mTc-chlorENS were always greater than 95% even after nebulization. The results of the biologic distribution studies showed that the activity concentration found in lungs for these radiopharmaceuticals were 95.7% +/- 2.6% and 96.7% +/- 2.6% respectively, results that do not differ statistically. On the other hand, the activity concentration found in lungs for the 99mTc-chlorlioENS (31.3% +/- 11.1%) and its labeling yield percentages (<10%) are statistically different (P < 0.05) from the results obtained with the two radiopharmaceuticals mentioned above. CONCLUSION: Taking into account the lioENS physicochemical properties, its long shelf life and that 99mTc-lioENS shows the same radiochemical and radiopharmacological behavior of the 99mTc-chlorENS, it can be concluded that the 99mTc-lioENS can be used for aerosol lung scintigraphy.

Radiochemical and radiopharmacological properties of pirocarbotrat and other labeled charcoal dispersions: comparative studies in rats with NMU-induced mammary tumors.

The purpose of this work is to study the physicochemical properties of Pirocarbotrat to explain its radiopharmacological behavior. We also studied a mixture of charcoal plus chromic [32P]phosphate and charcoal plus sodium [32P]orthophosphate only for comparative purposes. The results show that the mean diameter of the Pirocarbotrat particles was 2.5 microm with an homogeneous distribution, while the other products show an heterogeneous distribution of the particle sizes, with a mean size diameter between 0.5 and 0.9 microm. Hydrolysis studies with a solution of 0.1 N HCl and with sulfochromic mixture revealed that in Pirocarbotrat the 32P is strongly bound to the charcoal particles. Bioelimination studies of Pirocarbotrat show that the total eliminated activity was 12.70 +/- 3.90%, with a higher amount in urine (8.30 +/- 1.80%) than in feces (4.40 +/- 3.50%). When biodistribution studies of Pirocarbotrat were carried out, we found that the 84.50 +/- 2.60% of the activity remained in the tumor with almost null irradiation of the other organs under study. When therapeutic action was evaluated, we observed that the percentage of tumor regression was 78.3% for the tumors injected with Pirocarbotrat. The other dispersions under study showed different behaviors with high activity percentages distributed throughout the organism. These studies demonstrate that Pirocarbotrat has the best radiopharmacological properties to ensure irradiation of the tumor with the least concomitant irradiation of surroundings or other organs or tissues.

Pirocarbotrat: a new radiopharmaceutical for the treatment of solid tumors--comparative studies in N-nitrosomethylurea-induced rat mammary tumors.

To evaluate the effectiveness of a single intratumoral dose of Pirocarbotrat, a gelatin-protected charcoal suspension labeled with chromic [32P]pyrophosphate, studies of bioelimination, biodistribution and therapeutic action were carried out in rats, and the results obtained were compared with those of other 32P dispersions. We found that 78.3% of the treated tumors reduced size after 32 days of treatment. At that time, the total eliminated activity was 12.70 +/- 3.90% distributed in urine (8.30 +/- 1.80%) and feces (4.40 +/- 3.50%). Biodistribution studies demonstrate that 84.50 +/- 2.60% of the injected activity remained in the tumor, with no significant concentration in the rest of the organism. We conclude that Pirocarbotrat can be used as a safe agent for brachytherapy of solid tumors with beta particles.

[Brachytherapy of solid tumors. Use of chromic phosphate colloid]. / Braquiterapia de tumores sólidos. Uso del fosfato crómico coloidal.

With the purpose of studying the effectivity of an intratumoral single dose of chromic [32P] phosphate (Phosphocol) for the treatment of solid tumors, studies of bioelimination, biodistribution and therapeutic action were carried out in rats with experimental induced tumors. The results show that the percentage of total elimination is equal to 29.76 +/- 9.60% with a higher percentage in faeces 23.28 +/- 8.81% than in urine 6.48 +/- 2.11%. Biodistribution studies show that, 51.61 +/- 5.82% of the injected activity is found in the tumor while in organs with reticuloendothelial cells, the percentage of activity was 13.09 +/- 5.15% in liver and 2.88 +/- 1.23% in lung. On the other hand, when therapeutic action was evaluated, we found that the percentage of tumor regression (P.T.R) was 61.0% for the injected tumors. It is important to point out that 4 of the treated animals show bioelimination patterns in which the elimination rises suddenly at some time of the study. These results demonstrate that the use of this kind of colloids is not to be recommended for the treatment of solid tumors with moderated degree of vascularization, since its mobilization from the injection point may result in the consequent irradiation of different organs that are not under treatment.

Use of colloids of chromic [32P] phosphate in treatment of solid tumors.

In order to evaluate the effectiveness of an intratumorally single dose of chromic [32P] phosphate for the treatment of solid tumors, studies of bioelimination, biodistribution, and therapeutic action were carried out. Only for comparative purposes were similar studies undertaken using a solution of sodium [32P] orthophosphate-gelatin. Results show that when sodium [32P] orthophosphate-gelatin was intratumorally injected, the percentage of total elimination, after 32 days of treatment, was equal to 85.90 +/- 8.70%, with a higher percentage in urine (64.50 +/- 13.70%) than in feces (21.40 +/- 4.50%). In biodistribution studies, the greater percentage was found in bone (15.54 +/- 2.21%), whereas only 2.51 +/- 0.39% remained in the tumor. When chromic [32P] phosphate was intratumorally injected, we found that the total elimination was equal to 51.70 +/- 6.90%, with a higher amount in feces (32.70 +/- 4.80%) than in urine (19.00 +/- 3.60%). Biodistribution studies demonstrated that 28.93 +/- 1.30% was still in the tumor and 19.01 +/- 1.30% of the injected activity was found in the liver. On the other hand, when therapeutic action was evaluated, no tumoral regression was observed. These results demonstrate that the colloid of chromic [32P] phosphate cannot be used in the treatment of solid tumors as it mobilizes from the injection point, delivering a high dose to the entire organism.

Great particles [32P]chromic phosphate for treatment of solid tumors.

With the purpose of studying the effectivity of an intratumoral single dose of chromic [32P] phosphate with great particles for the treatment of solid tumors, studies of bioelimination, biodistribution and therapeutic action were carried out. Only for comparative purposes, similar studies were undertaken using a solution of sodium -32P- orthophosphate-gelatine. The results show that when sodium [32P] orthophosphate-gelatine is used, the percentage of total elimination is (85.90 +/- 8.70)% with a higher percentage in urine (64.50 +/- 13.70)% than in faeces (21.40 +/- 4.50)%. In biodistribution studies, the greater percentage is found in bone (15.54 +/- 2.21)% while only a (2.51 +/- 0.39)% remains in the tumor. When great particles chromic [32P]phosphate was intratumorally injected, we determined that the total elimination is equal (36.28 +/- 6.27)%, finding a higher amount in faeces (29.44 +/- 5.26)% than in urine (6.84 +/- 2.21)%. Biodistribution studies demonstrated that (49.82 +/- 5.41)% remains in the tumor and (9.63 +/- 4.89)% of the injected activity is found in the liver. On the other hand, when therapeutic action was evaluated, we observed that the percentage of tumor regression (P.T.R.) is 52.0% for the tumors injected with chromic [32P]phosphate and 0.0% for those injected with sodium [32P]orthophosphate-gelatine. These results show that the great particles colloid of chromic [32P]phosphate is not safe enough for the treatment of solid tumors, since it is mobilized from the injection point, delivering a high dose to the whole organism.

New methodology for pancreatic scintiscanning imaging using 125I-L-3 Iodo-alpha-Methyl Tyrosine.

The difficulty of a reliable diagnosis of pancreatic diseases by scintiscanning, is mainly derived from the lack of adequate radiopharmaceuticals. With this purpose 125I-L-3 Iodo-a-Methyl Tyrosine (125I-IMT) has been studied, which has also been used for the diagnosis of different kind of brain tumors. The purpose of this work is the development of a quick and easy method for the synthesis and purification of the 125I-IMT in order to be used in a Nuclear Medicine Service. The L-alpha-Methyl Tyrosine was labeled with 125I using I-/I03 and afterwards purified by an anionic exchange resin. The labeling yield obtained was (96.0 +/- 0.5)% when the incubation time was 15 minutes. No significant statistical differences were observed when the incubation time was extended to 1 hour. Biodistribution studies in mice show that the percentage of activity concentration in pancreas is (34.24 +/- 14.03)% at 15 minutes post injection, remaining constant for 30 minutes. The pancreas/liver ratio 15 minutes after the injection of the labeled product was (12.22 +/- 3.59) and it remained constant for 45 minutes more. These results show that 125I-IMT can be used as a diagnostic agent for pancreatic diseases. Since 123I was not available at the moment, this new methodology was developed with 125I.

New methodology for pancreatic scintiscanning imaging using 125I-L-3 iodo-alpha-methyl tyrosine

The difficulty of a reliable diagnosis of pancreatic diseases by scintiscanning, is mainly derived from the lack of adequate radiopharmaceuticals. With this purpose (125) I-L(-3) Iodo-a-Methyl Tyrosine ((125) I-IMT) has been studied, which has also been used for the diagnosis of different kind of brain tumors. The purpose of this work is the development of a quick and easy method for the synthesis and purification of the (125) I-IMT in order to be used in a Nuclear Medicine Service. The L-(-Methly Tyrosine was labeled with (125) I using I-/I03 and afterwards purified by an aniomic exchange resin. The labeling yield obtained was (96.0+0.5) per cent when the incubation time was 15 minutes. No significant statistical differences were observed when the incubation time was extended to 1 hour. Biodistribution studies in mice show that the percentage of activity concentration in pancreas is (34.24+14.03) per cent at 15 minutes post injection, remaining constant for 30 minutes. The pancreas/liver ratio 15 minutes after the injection of the labeled product was (12.22+3.59) and it remained constant for 45 minutes more. These results show that (125) I-IMT cab be used as a diagnostic agent for pancreatic diseases. Since (123) I was not avilable at the moment, this new methodology was developed with (125) I. (AU)

Great particles (32P) chromic phosphate for treatment of solid tumors

With the purpose studying the effectivity of an intratumoral single dose of chromic [(32)P] phosphate with great particles for the treatment of solid tumors, studies of biolimination, biodistribution and therapeutic action were carried out. Only for comparative purpose, similar studies were undertaken using a solution of sodium [(32)P] orthophosphategelatine. The results show that when sodium [(32)P] orthophosphategelatine is used, the percentage of total elimination is (85.90+8,70) per cent with a higler percentage in urine (64.50+13.70) per cent than in faeces (21.40+4.50) per cent. In biodistribution studies, the greater percentage is found in bone (15.54+2.21) per cent while only a (2.51+0.39) per cent remains in the tumor. When great particles chromic [(32)P] phosphate was intratumorally injected, we determined that the total elimination is equal (36.28+6.27) per cent, finding a higler amount in faeces (29.44+5.26) per cent than in urine (6.84+2.21) per cent. Biodistribution studies demonstrated that (49.82+5.41) per cent remains in the tumor and (9.63+4.89) per cent of the injected activity is found in the liver. On the other hand, when therapeutic action was evoluted, we observed that the percentage of tumor regression (P.T.R) is 52.0 per cent for the tumors injected with chromic [(32)P] phosphate and 0.0 per cent for those injected with sodium [(32)P] orthophosphate-gelatine. These results show that the great particles colloid of chromic [(32)P] phosphate is not safe enough for the tratment of solid tumors, since it is mobilezed from the injection point, delivering a high dose to the whole organism. (AU)

New methodology for pancreatic scintiscanning imaging using 125I-L-3 iodo-alpha-methyl tyrosine

The difficulty of a reliable diagnosis of pancreatic diseases by scintiscanning, is mainly derived from the lack of adequate radiopharmaceuticals. With this purpose (125) I-L(-3) Iodo-a-Methyl Tyrosine ((125) I-IMT) has been studied, which has also been used for the diagnosis of different kind of brain tumors. The purpose of this work is the development of a quick and easy method for the synthesis and purification of the (125) I-IMT in order to be used in a Nuclear Medicine Service. The L-(-Methly Tyrosine was labeled with (125) I using I-/I03 and afterwards purified by an aniomic exchange resin. The labeling yield obtained was (96.0+0.5) per cent when the incubation time was 15 minutes. No significant statistical differences were observed when the incubation time was extended to 1 hour. Biodistribution studies in mice show that the percentage of activity concentration in pancreas is (34.24+14.03) per cent at 15 minutes post injection, remaining constant for 30 minutes. The pancreas/liver ratio 15 minutes after the injection of the labeled product was (12.22+3.59) and it remained constant for 45 minutes more. These results show that (125) I-IMT cab be used as a diagnostic agent for pancreatic diseases. Since (123) I was not avilable at the moment, this new methodology was developed with (125) I.

Great particles (32P) chromic phosphate for treatment of solid tumors

With the purpose studying the effectivity of an intratumoral single dose of chromic [(32)P] phosphate with great particles for the treatment of solid tumors, studies of biolimination, biodistribution and therapeutic action were carried out. Only for comparative purpose, similar studies were undertaken using a solution of sodium [(32)P] orthophosphategelatine. The results show that when sodium [(32)P] orthophosphategelatine is used, the percentage of total elimination is (85.90+8,70) per cent with a higler percentage in urine (64.50+13.70) per cent than in faeces (21.40+4.50) per cent. In biodistribution studies, the greater percentage is found in bone (15.54+2.21) per cent while only a (2.51+0.39) per cent remains in the tumor. When great particles chromic [(32)P] phosphate was intratumorally injected, we determined that the total elimination is equal (36.28+6.27) per cent, finding a higler amount in faeces (29.44+5.26) per cent than in urine (6.84+2.21) per cent. Biodistribution studies demonstrated that (49.82+5.41) per cent remains in the tumor and (9.63+4.89) per cent of the injected activity is found in the liver. On the other hand, when therapeutic action was evoluted, we observed that the percentage of tumor regression (P.T.R) is 52.0 per cent for the tumors injected with chromic [(32)P] phosphate and 0.0 per cent for those injected with sodium [(32)P] orthophosphate-gelatine. These results show that the great particles colloid of chromic [(32)P] phosphate is not safe enough for the tratment of solid tumors, since it is mobilezed from the injection point, delivering a high dose to the whole organism.