The widespread application of positron emission tomography (PET) in clinical oncology has driven this imaging technology into a number of new research and clinical arenas. Increasing numbers of patient scans have led to an urgent need for efficient data handling and the development of new image analysis techniques to aid clinicians in the diagnosis of disease and planning of treatment. Automatic quantitative assessment of metabolic PET data is attractive and will certainly revolutionize the practice of functional imaging since it can lower variability across institutions and may enhance the consistency of image interpretation independent of reader experience. In this paper, a novel automated system for the segmentation of oncological PET data aiming at providing an accurate quantitative analysis tool is proposed. The initial step involves expectation maximization (EM)-based mixture modeling using a k-means clustering procedure, which varies voxel order for initialization. A multiscale Markov model is then used to refine this segmentation by modeling spatial correlations between neighboring image voxels. An experimental study using an anthropomorphic thorax phantom was conducted for quantitative evaluation of the performance of the proposed segmentation algorithm. The comparison of actual tumor volumes to the volumes calculated using different segmentation methodologies including standard k-means, spatial domain Markov Random Field Model (MRFM), and the new multiscale MRFM proposed in this paper showed that the latter dramatically reduces the relative error to less than 8% for small lesions (7 mm radii) and less than 3.5% for larger lesions (9 mm radii). The analysis of the resulting segmentations of clinical oncologic PET data seems to confirm that this methodology shows promise and can successfully segment patient lesions. For problematic images, this technique enables the identification of tumors situated very close to nearby high normal physiologic uptake. The use of this technique to estimate tumor volumes for assessment of response to therapy and to delineate treatment volumes for the purpose of combined PET/CT-based radiation therapy treatment planning is also discussed.

Intracranial neoplasia is a significant cause of morbidity and mortality in both human and veterinary patients, and is difficult to treat with traditional therapeutic methods. Cisplatin is a platinum (Pt)-containing chemotherapeutic agent approved by the Food and Drug Administration; however, substantial limitations exist for its application in canine brain tumor treatment due to the difficulty in crossing the blood-brain barrier (BBB), development of resistance, and toxicity. A modified Pt(iv)-prodrug of cisplatin, Platin-M, was recently shown to be deliverable to the brain via a biocompatible mitochondria-targeted lipophilic polymeric nanoparticle (NP) that carries the drug across the BBB and to the mitochondria. NP mediated controlled release of Platin-M and subsequent reduction of this prodrug to cisplatin allowed cross-links to be formed with the mitochondrial DNA, which have no nucleotide excision repair system, forcing the overactive cancer cells to undergo apoptosis. Here, we report in vitro effects of targeted Platin-M NPs (T-Platin-M-NPs) in canine glioma and glioblastoma cell lines with results indicating that this targeted NP formulation is more effective than cisplatin. In both the cell lines, T-Platin-M-NP was significantly more efficacious compared to carboplatin, another Pt-based chemotherapy, which is used in the settings of recurrent high-grade glioblastoma. Mitochondrial stress analysis indicated that T-Platin-M-NP is more effective in disrupting the mitochondrial bioenergetics in both the cell types. A 14-day distribution study in healthy adult beagles using a single intravenous injection at 0.5 mg kg(-1) (with respect to Platin-M) of T-Platin-M-NPs showed high levels of Pt accumulation in the brain, with negligible amounts in the other analyzed organs. Safety studies in the beagles monitoring physical, hematological, and serum chemistry evaluations were within the normal limits on days 1, 7, and 14 after injection of either 0.5 mg kg(-1) or 2 mg kg(-1) or 2.2 mg kg(-1) (with respect to Platin-M) of T-Platin-M-NPs. At all doses over the 14-day period, no neurotoxicity was observed based upon periodic neurological examinations and cerebrospinal fluid analysis. These studies demonstrated the translational nature of T-Platin-M-NPs for applications in the treatment of brain tumors.

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