Umber A. Salman

Positron emission tomography (PET)

Positron emission tomography (PET) allows three-dimensional quantitative determination of the distribution of radioactivity permitting measurement of physiological, biochemical, and pharmacological functions at the molecular level. Until recently, no method existed to directly and noninvasively assess transport and metabolism of neoplastic agents as a function of time in various organs as well as in the tumor. Standard preclinical evaluation of potential anticancer agents entails radiolabeling the agent, usually with tritium or 14C, sacrifice experiments, and high-performance liquid chromatography (HPLC) analysis to determine the biodistribution and metabolism in animals. Radiolabeling agents with positron-emitting radionuclides allows the same information to be obtained as well as in vivo pharmacokinetic (PK) data by animal tissue and plasma sampling in combination with PET scanning. In phase I/II human studies, classic PK measurements can be coupled with imaging measurements to define an optimal dosing schedule and help formulate the design of phase III studies that are essential for drug licensure [1]. Many of the novel agents currently in development are cytostatic rather than cytotoxic and therefore, the traditional standard endpoints in phase I and II studies may no longer be relevant. The use of a specialized imaging modality that allows PK and pharmacodynamic (PD) evaluation of a drug of interest has been proposed to permit rapid and sensitive assessment of the biological effects of novel anticancer agents. The progress to date and the challenges of incorporating PET technology into oncology drug development from the preclinical to clinical setting are reviewed in this article.

Positron emission tomography (PET): expanding the horizons of oncology drug development.

Positron emission tomography (PET) allows three-dimensional quantitative determination of the distribution of radioactivity permitting measurement of physiological, biochemical, and pharmacological functions at the molecular level. Until recently, no method existed to directly and noninvasively assess transport and metabolism of neoplastic agents as a function of time in various organs as well as in the tumor. Standard preclinical evaluation of potential anticancer agents entails radiolabeling the agent, usually with tritium or 14C, sacrifice experiments, and high-performance liquid chromatography (HPLC) analysis to determine the biodistribution and metabolism in animals. Radiolabeling agents with positron-emitting radionuclides allows the same information to be obtained as well as in vivo pharmacokinetic (PK) data by animal tissue and plasma sampling in combination with PET scanning. In phase I/II human studies, classic PK measurements can be coupled with imaging measurements to define an optimal dosing schedule and help formulate the design of phase III studies that are essential for drug licensure [1]. Many of the novel agents currently in development are cytostatic rather than cytotoxic and therefore, the traditional standard endpoints in phase I and II studies may no longer be relevant. The use of a specialized imaging modality that allows PK and pharmacodynamic (PD) evaluation of a drug of interest has been proposed to permit rapid and sensitive assessment of the biological effects of novel anticancer agents. The progress to date and the challenges of incorporating PET technology into oncology drug development from the preclinical to clinical setting are reviewed in this article.

Current controversies in the initial post-surgical radioactive iodine therapy for thyroid cancer: a narrative review

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy and the fifth most common cancer in women. DTC therapy requires a multimodal approach, including surgery, which is beyond the scope of this paper. However, for over 50 years, the post-operative management of the DTC post-thyroidectomy patient has included radioactive iodine (RAI) ablation and/or therapy. Before 2000, a typical RAI post-operative dose recommendation was 100 mCi for remnant ablation, 150 mCi for locoregional nodal disease, and 175-200 mCi for distant metastases. Recent recommendations have been made to decrease the dose in order to limit the perceived adverse effects of RAI including salivary gland dysfunction and inducing secondary primary malignancies. A significant controversy has thus arisen regarding the use of RAI, particularly in the management of the low-risk DTC patient. This debate includes the definition of the low-risk patient, RAI dose selection, and whether or not RAI is needed in all patients. To allow the reader to form an opinion regarding post-operative RAI therapy in DTC, a literature review of the risks and benefits is presented.

Gastric emptying of beer in Mexican-Americans compared with non-Hispanic whites

Gastric emptying studies were performed on 11 nondiabetic Mexican-Americans and 11 nondiabetic non-Hispanic whites following ingestion of 450 mL beer. Plasma glucose, serum insulin, and serum alcohol levels were measured in the fasting state and at 7, 15, 30, 45, and 60 minutes following ingestion of the beer. The area under the gastric emptying curve was significantly larger for non-Hispanic whites compared with Mexican-Americans (P = .0492), indicating that Mexican-Americans had faster stomach emptying. Partial correlation coefficients (adjusted for ethnicity, gender, age, and body mass index [BMI]) showed the gastric half-emptying time was inversely related to the incremental levels of glucose (r = -.709, P = .0010) and alcohol (r = -.650, P = .0035). The faster the rate of gastric emptying of beer, the higher the glucose and alcohol levels. There were no significant correlations between insulin and the rate of gastric emptying. The caloric emptying rate for the beer was much more rapid than previously reported for other liquid meals.

Ocular silicone oil in the lateral cerebral ventricle

Silicone oil used for endotamponade of retinal detachment may migrate into the subarachnoid space of the brain, including the cerebral ventricles, presumably by extension through silicone oil-filled spaces in the optic nerve. Silicone oil has characteristic appearances on CT scans and MRI, which can be utilized to distinguish it from more ominous entities. We describe a case of intraventricular silicone in a patient who presented with seizures.