Feasibility study of particle-assisted laser ablation of brain tumors in orthotopic canine model.

We report on a pilot study showing a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photothermal ablation of canine transmissible venereal tumor (cTVT) in a canine brain model. cTVT fragments grown in severe combined immunodeficient mice were successfully inoculated in the parietal lobe of immunosuppressed, mixed-breed hound dogs. A single dose of near-IR (NIR)-absorbing, 150-nm nanoshells was infused i.v. and allowed time to passively accumulate in the intracranial tumors, which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT, suggesting that its neovasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, NIR radiation using a 3.5-W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8 +/- 4.1 degrees C. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sublethal temperatures of 48.6 +/- 1.1 degrees C. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Postmortem histopathology of treated brain sections showed the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

Immunohistochemical determination of estrogen receptor-alpha in vaginal and tumor tissues of healthy and TVT-affected bitches and their relation to serum concentrations of estradiol-17beta and progesterone.

One of the most frequent canine neoplasms is the transmissible venereal tumor (TVT), which affects the male and the female genital tract. The objective of this study was to determine (immunohistochemically) estrogen receptor (ER-alpha) expression in vaginal tissue of healthy bitches and in the vaginal and neoplastic tissues of TVT-affected bitches. Fifty-eight bitches were divided into two groups: tumor group (TVT) and control group (healthy). Canine estrous cycle stages were determined by means of exfoliative vaginal cytology, hormone assays, and macroscopic appearance of ovaries. Samples from vaginal and neoplastic tissues were obtained under general anesthesia, fixed in 10% buffered formaldehyde, embedded in paraffin, and sectioned. Anestrus, proestrus and estrus control females had higher ER-alpha expression than diestrus bitches. Within the tumor group, diestrus bitches had significantly higher ER-alpha expression. Although some samples had expression in the endothelium of blood vessels, no ER-alpha expression was observed in neoplastic tissues. In conclusion, vaginal tissue of tumor and control bitches, under different distinct steroid influences, had different ER-alpha expression, whereas ER-alpha expression was not present in neoplastic tissues.

Improved coagulation with saline solution pretreatment during radiofrequency tumor ablation in a canine model.

PURPOSE: To determine whether pretreatment with local NaCl injection can increase radiofrequency (RF)-induced coagulation in a large animal model. MATERIAL AND METHODS: Multiple canine venereal sarcomas (n = 25) were implanted subcutaneously in eight mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to a diameter of 4.2-6.3 cm (5.1 cm +/- 0.7). Internally cooled RF ablation (1-cm tip; 12 min; pulsed technique; 2,000-mA maximum) was performed. Tumors were pretreated with 6 mL of 18%, 24%, or 36% NaCl injected intratumorally under direct ultrasound guidance after RF electrode insertion, and this treatment was compared to RF treatment without NaCl injection and to 36% NaCl injection without RF ablation. Impedance measurements and remote thermometry were performed. These measurements and resultant coagulation were compared. RESULTS: Significantly greater RF heating (73 degrees C +/- 11 degrees C at 20 mm) was observed when the tumors were treated with 24% or 36% NaCl pretreatment, compared to the 47 degrees C +/- 5 degrees C observed when 18% or no NaCl was injected (P <.02). In the 36% NaCl group, the entire tumor (5.2 cm +/- 0.8 diameter) was completely ablated in every case, with coagulation extending several centimeters into the surrounding tissues. By comparison, control tumors (without NaCl injection) contained coagulation measuring 3.1 cm +/- 0.2, surrounded by viable, well-perfused tumor (P <.01), and 36% NaCl alone produced 2.7 cm +/- 0.6 of patchy necrosis. CONCLUSIONS: Pretreatment with intratumoral injection of small volumes of highly concentrated NaCl markedly increases RF heating and coagulation in a large animal tumor model. The complete destruction of tumors 5 cm in diameter or larger suggests that this substantial increase may be achieved for tumor ablation in clinical practice.