Spatial dose distributions in solid tumors from 186Re transported by liposomes using HS radiochromic media.

PURPOSE: A procedure for the measurement of spatial dose rate distribution of beta particles emitted by 186Re-liposomes in tumoral tissue, using HS GafChromic films, is presented. METHODS: HNSCC xenografts were intratumorally injected with 3.7 or 11.1 MBq of 186Re-liposomes, and planar gamma camera images were acquired to determine the liposome retention in the tumor. After imaging, rats were sacrificed and tumors were excised and processed in slices; HS film sections were placed between slices and the tumor lobe was reassembled. Tumors and films were kept in the dark at 4 degrees C for 18 h. After irradiation, films were removed and response was read using a transmission scanner. Films were analyzed to determine two-dimensional spatial dose rate distributions and cumulative dose volume histograms. Dose rate distributions were quantified using a 60Co calibration curve, the 186Re physical half-life, and a perturbation factor that takes into account the effect of the film protective layer. RESULTS: Dose rate distributions are highly heterogeneous with maximal dose rates about 0.4 Gy h(-1) in tumors injected with 3.7 MBq and 1.3 Gy h(-1) in tumors injected with 11.1 MBq. Dose volume histograms showed dose distributed in more than 95% and 80% of the tumor when injected with the lower and the higher activity, respectively. CONCLUSION: The described procedures and techniques have shown the potential and utility of HS GafChromic film for determination of dose rate distributions in solid tumors injected intratumorally with 186Re-liposomes. The film's structure and the liposomes' biodistribution must be taken into account to obtain quantitative dose measurements.

Mediastinal node and diaphragmatic targeting after intracavitary injection of avidin/99mTc-blue-biotin-liposome system.

A method for delivering drugs to sites of disease extension in mediastinal nodes is described. Mediastinal node and lymphatic distributions were determined after intracavitary injection of the avidin/biotin-liposome system in normal rats. The effect of the injected dose on lymphatic targeting of liposomes after intraperitoneal injection of (99m)Tc-blue-biotin-liposomes and intrapleural injection of avidin, and vice versa, is presented. Scintigraphic imaging was used to follow the movement of (99m)Tc-blue-biotin-liposomes to determine the pharmacokinetics and organ uptake. Tissue biodistribution studies were performed 22 h after injection of the (99m)Tc-blue-biotin-liposomes. Results indicated that independent of the cavity in which each agent was injected, a dose of 5.0 mg of each agent results in higher mediastinal node targeting (8%-10% ID/Organ) as compared with the injection of a 0.5 mg dose (2%-5% ID/Organ, p < 0.05). Targeting of diaphragm and associated lymphatics was observed when (99m)Tc-blue-biotin-liposomes were injected in peritoneum and avidin in pleural space. In contrast, pleural, and pericardial lymphatic targeting was observed when (99m)Tc-blue-biotin-liposomes were injected in pleural space and avidin in peritoneum. Intracavitary injection of the avidin/biotin-liposome system could potentially be used for the delivery of prophylactic drugs that could reduce tumor metastasis and infection spread to mediastinal nodes.

Estudo randomizado comparativo entre o cloridrato de ticlopidina e a aspirina, na prevencao de acidente vascular cerebral em paciente de alto risco

Este artigo relata os resultados do Estudo Ticlopidina-Aspirina em AVC, estudo duplo-cego realizado em 56 centros norte-americanos com o objetivo de comparar os efeitos do cloridrato de ticlopidina (500mg ao dia) com os da aspirina (1300mg ao dia) sobre o risco de acidente vascular cerebral ou morte. Os dois tratamentos foram distribuidos aleatoriamente entre os 3.069 pacientes, que apresentavam quadro recente transitorio, ou leve e persistente de isquemia retiniana ou cerebral focal. O periodo de acompanhamento variou de dois a seis anos. A incidencia de acidente vascular cerebral nao fatal ou de morte por qualquer causa apos tres anos foi de 17 por cento no grupo tratado com ticlopidina e de 19 por cento no grupo aspirina - houve reducao de 12 por cento do risco (intervalo de confianca 95 por cento, -2 a 26 por cento) com a ticlopidina (p=0,048 na estimativa acumulada de Kaplan-Meier). A incidencia de acidente vascular cerebral fatal e nao-fatal apos tres anos foi de 10 por cento no grupo de ticlopidina e de 13 por cento no grupo aspirina - reducao de 21 por cento no risco (intervalo de confianca 95 por cento, 4 a 38 por cento) com a ticlopidina (p=0,024 na analise acumulada de kaplan-Meier). a ticlopidina mostrou eficacia superior a da aspirina em ambos os sexos. Os efeitos adversos da aspirina foram diarreia (10 por cento), erupcao cutanea (5,5 por cento), ulcera (3 por cento), gastrite (2 por cento) e sangramento gastrointestinal (1 por cento). Com a ticlopidina foram observados os seguintes efeitos colaterais: diarreia (20 por cento), erupcao cutanea (14 por cento) e neutropenia acentuada porem reversivel (menos de 1 por cento). A relacao entre os niveis de lipoproteinas de alta e baixa densidade e o colesterol total foi a mesma nos dois grupos. O aumento medio dos niveis de colesterol total foi de 9 por cento com a ticlopidina e 2 por cento com a aspirina (p>0,01). Concluimos que a aspirina na prevencao de acidente vascular cerebral na populacao estudada, embora tenha provocado maior incidencia de efeitos colaterais.