Gold nanoparticle based X-ray contrast agent for tumor imaging in mice and dog: a potential nano-platform for computer tomography theranostics.

The goal of our study was to demonstrate the utility of nanocrystalline gold as an X-ray contrast agent for imaging tumor in living subjects. Even though significant progress has been achieved in this area by researchers, clinical translation remains challenging. Here, we investigated biocompatible gum Arabic stabilized gold nanocrystals (GA-AuNPs) as X-ray contrast agent in tumor bearing mice and dog. Single intratumoral injections of GA-AuNP resulted in X-ray contrast change of -26 HU in the tumor region after 1 hour post-injection period. Subsequently, five intratumoral injections were performed in the mice. The change in CT number in tumor region is not progressive; rather it reaches a saturation point after fourth injection. These data suggested that accumulation of GA-AuNP reaches a threshold limit within a short time period (5 h), and is retained in the tumor tissue for the rest of the period of investigation. A pilot study was conducted in a client-owned dog presented with collision tumor of thyroid carcinoma and osteosarcoma. In this study, GA-AuNP was injected intratumorally in dog and a contrast enhancement of 12 deltaHU was observed. The CT images of both mice and dog clearly demonstrated that GA-AuNP was effectively distributed and retained throughout the tumor site. The CT data obtained by the present study would provide the crucial dosimetry information for strategic therapy planning using this construct. Both mice and dog did not show any clinical changes, thereby confirming that GA-AuNP did not induce toxicity and can be explored for future clinical applications.

Canine prostatic carcinoma.

Canine prostatic carcinoma is locally aggressive with a high rate of metastasis. Common metastatic sites include lymph nodes, lungs, liver, spleen, and bone. Staging relies on chest radiography, abdominal radiography, and abdominal ultrasonography, in addition to radiography of any painful regions. An enlarged, mineralized prostate is a frequent finding; in a castrated male dog, it is predictive of prostatic carcinoma. NSAIDs are an important component of treatment, although additional local and systemic therapies should be considered to improve the quality of life of these patients.

Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs.

BACKGROUND: Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs. METHODS: Three normal adult hound dogs were evaluated by physical examination, complete blood count, chemistry profile, and urinalysis. Dogs were treated with staggered escalating dosages of CTI 52010 with a 28-day washout. All dogs were treated with a starting dosage of 40 mg/m(2), and subsequent dosages were escalated at 50% (dog 1), 100% (dog 2), or 200% (dog 3) with each cycle, to a maximum of 240 mg/m(2). Dogs were monitored by daily physical assessment and weekly laboratory evaluation. Standard criteria were used to grade adverse events. Plasma was collected at regular intervals to determine pharmacokinetics. Dogs were euthanized humanely, and necropsy was performed one week after the last treatment. RESULTS: The dose-limiting toxicity was grade 4 neutropenia and the maximum tolerated dosage was 120 mg/m(2). Grade 1-2 gastrointestinal toxicity was noted at higher dosages. Upon post mortem evaluation, no evidence of organ (liver, kidney, spleen) toxicity was noted. CONCLUSION: CTI 52010 was well tolerated when administered intravenously to normal dogs. A starting dosage for a Phase I/II trial in tumor-bearing dogs is 80 mg/m(2).

Blunted pathogen-associated molecular pattern motif induced TNF, IL-6 and IL-10 production from whole blood in dogs with lymphoma.

Lymphoma is associated with a higher risk of sepsis as compared to other forms of neoplasia in people and dogs which might be due to alterations in cytokine production. The objective of this study was to compare bacterial pathogen associated molecular pattern (PAMP) motif-induced TNF, IL-6, and IL-10 response of whole blood from dogs with naïve lymphoma and healthy dogs. We hypothesized that whole blood from dogs with lymphoma would exhibit an impaired cytokine response to LPS, lipoteichoic acid (LTA), and peptidoglycan (PG) stimulation compared to whole blood from healthy dogs. Whole blood was collected from dogs with lymphoma (n=20) and healthy dogs (n=15) and stimulated with PAMPs or phosphate buffered saline. Whole blood production of TNF, IL-6 and IL-10 was measured. Whole blood from dogs with lymphoma had reduced TNF, IL-6 and IL-10 production capacity after LPS, LTA and PG stimulation compared to whole blood from healthy dogs. These data could partially explain why dogs with lymphoma have a higher risk for infection compared to dogs with other forms of neoplasia.

Hematologic changes associated with half-body irradiation in dogs with lymphoma.

BACKGROUND: Reports describe the technique and efficacy of half-body irradiation (HBI) of dogs with lymphoma, but few describe the distinctive toxicoses associated with the combination of HBI and chemotherapy. HYPOTHESIS: HBI would transiently affect myelocytic and erythroid variables as assessed by serial analysis of complete blood counts. ANIMALS: Twenty-nine dogs with lymphoma treated with HBI during 2002 and 2003. METHODS: A retrospective study of medical records of 29 dogs was performed. Two HBI protocols were used, resulting in delivery of either 6 Gy or 8 Gy to each half of the body, 1 month apart. Dogs received chemotherapy before, during, or after irradiation, or at multiple times. Serial hematology was available for all dogs. Data were analyzed between collection periods by analysis of variance (ANOVA) RESULTS: The mean granulocyte count significantly (P < .01) decreased from 10,017 cells/microL (data range 3,001-20,170 cells/ microL) before the first radiation treatment to 3,250 cells/microL (820-4,400 cells/microL) at week 5 (P < .01). Three weeks after this nadir, the mean increased to 10,150 cells/microL (900-26,700 cells/microL). The hematocrit did not change (36-38%). Thrombocytopenia (<100,000/microL) occurred in 10 dogs. Two dogs died because of complications associated with thrombocytopenia. No significant difference in toxicity was found between the 6 Gy and 8 Gy group. CONCLUSIONS AND CLINICAL IMPORTANCE: HBI was myelosuppressive but effects were short term and resolved in 22 of 24 dogs. Further studies are needed to elucidate the safety and role of HBI in the treatment of dogs with lymphoma.