A Heat‐Activated Drug‐Delivery Platform Based on Phosphatidyl‐(oligo)‐glycerol Nanocarrier for Effective Cancer Treatment

The potential of cancer drugs is not fully exploited due to low tumor uptake and occurrence of systemic side effects, limiting maximum tolerated dose. Actively targeted nanocarriers improve efficacy while minimizing off‐target toxicity. Herein, it is the first time a drug‐delivery platform for heat‐triggered intravascular drug release is described, based on synthetic phosphatidyl‐(oligo)‐glycerols from organic synthesis to preclinical investigation in feline patients. For the nanocarrier formulated doxorubicin (DOX), superior tumor drug delivery and antitumor activity compared with free DOX, conventional liposomal DOX (Caelyx), and temperature‐sensitive lysolipid‐containing DOX‐liposomes in rat sarcoma are demonstrated. In a comparative oncological study with neoadjuvant treatment of feline sarcoma, a metabolic response determined with 18 F‐FDG‐positron emission tomography/magnetic resonance imaging (PET/MRI) and histopathological response after tumor resection are significantly better compared with free DOX, potentially by overcoming drug resistance based on improved intratumoral drug distribution. This novel drug‐delivery platform has great potential for the treatment of locally advanced tumors in humans

Comparative Oncology: Evaluation of 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) for the Staging of Dogs with Malignant Tumors.

Introduction2-Deoxy-2-[18F]fluoro-D-glucose PET/CT is a well-established imaging method for staging, restaging and therapy-control in human medicine. In veterinary medicine, this imaging method could prove to be an attractive and innovative alternative to conventional imaging in order to improve staging and restaging. The aim of this study was both to evaluate the effectiveness of this image-guided method in canine patients with spontaneously occurring cancer as well as to illustrate the dog as a well-suited animal model for comparative oncology.MethodsTen dogs with various malignant tumors were included in the study and underwent a whole body FDG PET/CT. One patient has a second PET-CT 5 months after the first study. Patients were diagnosed with histiocytic sarcoma (n = 1), malignant lymphoma (n = 2), mammary carcinoma (n = 4), sertoli cell tumor (n = 1), gastrointestinal stromal tumor (GIST) (n = 1) and lung tumor (n = 1). PET/CT data were analyzed with the help of a 5-point scale in consideration of the patients' medical histories.ResultsIn seven of the ten dogs, the treatment protocol and prognosis were significantly changed due to the results of FDG PET/CT. In the patients with lymphoma (n = 2) tumor extent could be defined on PET/CT because of increased FDG uptake in multiple lymph nodes. This led to the recommendation for a therapeutic polychemotherapy as a treatment. In one of the dogs with mammary carcinoma (n = 4) and in the patient with the lung tumor (n = 1), surgery was cancelled due to the discovery of multiple metastasis. Consequently no treatment was recommended.ConclusionFDG PET/CT offers additional information in canine patients with malignant disease with a potential improvement of staging and restaging. The encouraging data of this clinical study highlights the possibility to further improve innovative diagnostic and staging methods with regard to comparative oncology. In the future, performing PET/CT not only for staging but also in therapy control could offer a significant improvement in the management of dogs with malignant tumors

SUV max values in organs.

<p>Primary tumor measured in patient numbers 2,4,5,8,9,10.</p><p>Solid and lymph node (suspected) metastases are defined separately in table.</p><p>SUV max values in organs.</p

18F-FDG uptake in a patient with multicentric lymphoma.

<p>(A) Coronal contrast enhanced computer tomography (CT); (B) Coronal 18F-fluoro-2-deoxy-D- glucose (18F-FDG positron emission tomography (PET)/CT) Increased FDG uptake in both retropharyngales lymph nodes (standardized uptake value (SUV) mean 2.37 and 2.43 ± 2.4) as well as intramuscular increased FDG-uptake (SUV mean 3.04 ± 1.25).</p

Patient Characteristics.

<p>Personal description and treatment of every patient before PET/CT</p><p>Chlorethyl-Cyclohexyl-Nitroso-Urea (CCNU)/ Lomustin.</p><p>Patient Characteristics.</p

Mean and Max SUVs.

<p>Abnormal findings with increased uptake in PET/CT with their cytologic or histologic or differential diagnosis in individual patients.</p><p>Mean and Max SUVs.</p

Findings of PET/CT, resulting therapeutic decisions and clinical follow-up.

<p>Results of PET/CT; in every patient the SUVs of the local and regional lymph nodes as well as the main target areas of metastases were measured for accommodating the prognosis and following therapy individually. Abnormal findings in CT as well as increased FDG uptake were classified with the help of the 5-point scale.</p><p>Findings of PET/CT, resulting therapeutic decisions and clinical follow-up.</p

18F F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in a patient with mammary carcinoma and multiple metastases.

<p>(A) Axial contrast enhanced computer tomography (CT); (B) Axial 18F-FDG positron emission tomography (PET)/CT Increased FDG uptake in the primary tumor (SUV mean 6.92 ± 1.06), histologically a mammary carcinoma on the mammary gland; hepatomegaly; mass within the spleen with increased 18F- FDG uptake (SUV mean 2.91 ± 0.31).</p