PURPOSE: A dose-response study was performed in swine to investigate the vascular effects of 32P over a broad range of doses in order to define the therapeutic window of intracoronary radiotherapy (ICR) with 32P. METHODS AND MATERIALS: A total of 131 porcine arteries were subjected to balloon injury or stenting followed by 0-36 Gy of ICR from a centered 32P source wire to 1 mm beyond lumen surface or a sham ICR procedure. Animals were euthanized at 4 weeks, and vessels were harvested for histomorphometry. RESULTS: In the balloon-injured arteries, doses of 7 and 9 Gy did not impact restenosis. At doses of 14-36 Gy, neointima was markedly reduced, with mild dilatation at the highest dose, 36 Gy. In the stent-injured arteries, the lowest dose of 9 Gy failed to reduce neointimal growth, while 14-26 Gy showed the most favorable response. CONCLUSIONS: ICR with 32P features a broad therapeutic window. Doses of 14-26 Gy to 1 mm beyond lumen surface provided an optimal combination of efficacy and safety. Doses of 7 and 9 Gy were generally ineffective, suggesting a minimum threshold for ICR with 32P to effectively inhibit restenosis.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Is the pathology of radiation injury different in small vs large blood vessels?

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Animals↗

PubMedDate not supplied

Endothelial cells and hyperthermia.

Most radiation oncologists are aware of the effects of clinical hyperthermia on neoplastic cells. Its effects on blood vessels, however, are not as well recognized. Yet, since the 1960s a number of investigators have described and categorized the effects of hyperthermia on microvessels (in vivo), and on cultured endothelial cells (EC) (in vitro). Both EC and microvessels can be lethally damaged by the hyperthermia doses used as antineoplastic therapy. In vitro data indicate that capillary EC are moderately sensitive to hyperthermia. Proliferating EC are more thermosensitive suggesting that microvessels of malignant neoplasms (which contain many proliferating EC) are more affected than microvessels of normal tissues. This differential sensitivity of microvessels has also been observed in blood flow studies. Furthermore, hyperthermia inhibits angiogenesis. Thus, some of the antineoplastic effects of heat are caused by ischaemia due to obstruction or destruction of the tumour vessels or to inability to form new vessels. Sublethal EC damage can also be demonstrated, resulting in decreased synthesis of most proteins including adhesion molecules (as well as increased expression of a few such as heat shock proteins) and producing reversible loss of cytoskeletal elements. The therapeutic advantage provided by the higher thermal sensitivity of neoplastic vessels should be exploited further, perhaps by developing strategies specifically aimed to the tumour microvasculature.

Animals↗

PubMedDate not supplied

[Malnutrition and poverty in Colombia].

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Age Factors↗

PubMedDate not supplied

Safety of 125iodine and 192iridium implants to the canine carotid artery. Long-term results.

Thirty-nine healthy dogs underwent a simulated radical neck dissection followed by implantation of either 125Iodine (125I) or 192Iridium (192Ir) in various dose regimes randomized prospectively from 3,000 to 30,000 rad. Bilateral selective carotid angiography was performed immediately postoperatively and at 6, 12, 18, and 24 months. No significant effects occurred to the animals who received 15,000 rad 125I or 6,000 rad 192Ir. In the higher dosed animals the 125I-treated group fared better than the 192Ir-treated group, probably due to the lower dose rate delivery. Fewer and less serious complications occurred in the 125I-treated group, but this group developed more complications after one year than the Iridium group.

Animals↗

PubMedDate not supplied

Pharmacokinetics of indium-111 BLEDTA in man.

111In-BLEDTA is a bleomycin-containing radiopharmaceutical that has proven useful as a tumor imaging agent. Whole blood distribution and pharmacokinetic parameters were studied in nine cancer patients, and the results compared with previously reported studies using 57Co-bleomycin. In eight patients studied by bolus intravenous injection, 111In-BLEDTA had a beta half-life (t1/2 beta) of 1.3 hours, a terminal-phase half-life (t1/2) of 11.7 hours, a volume of distribution (Vd gamma) of 57.5L/m2, a total body clearance rate (C1b) of 52.8 ml/min/m2, a renal clearance rate (C1r) of 23.3 ml/min/m2, and a 24-hour urinary excretion of 38.1% total administered dose. 111In-BLEDTA and 57Co-bleomycin have similar C1bs but differing Vds. Polymorphonuclear cell uptake of 111In-BLEDTA may explain its shorter t1/2 beta and t1/2, as well as its lower C1r and 24-hour urinary excretion. While the biologic characteristics of 111In-BLEDTA contribute to a greater background activity than is observed in scans with 57Co-bleomycin, its superior physical properties render it clinically more desirable as a tumor-imaging radiopharmaceutical.

Adult↗