Assessment of near-infrared fluorophores to study the biodistribution and tumor targeting of an IL13 receptor α2 antibody by fluorescence molecular tomography.

Non-invasive imaging using radiolabels is a common technique used to study the biodistribution of biologics. Due to the limited shelf-life of radiolabels and the requirements of specialized labs, non-invasive optical imaging is an attractive alternative for preclinical studies. Previously, we demonstrated the utility of fluorescence molecular tomography (FMT) an optical imaging modality in evaluating the biodistribution of antibody-drug conjugates. As FMT is a relatively new technology, few fluorophores have been validated for in vivo imaging. The goal of this study was to characterize and determine the utility of near-infrared (NIR) fluorophores for biodistribution studies using interleukin-13 receptor subunit alpha-2 antibody (IL13Rα2-Ab). Eight fluorophores (ex/em: 630/800 nm) with an N-hydroxysuccinimide (NHS) linker were evaluated for Ab conjugation. The resulting antibody-fluorophore (Ab-F) conjugates were evaluated in vitro for degree of conjugation, stability and target-binding, followed by in vivo/ex vivo FMT imaging to determine biodistribution in a xenograft model. The Ab-F conjugates (except Ab-DyLight800) showed good in vitro stability and antigen binding. All Ab-F conjugates (except for Ab-BOD630) resulted in a quantifiable signal in vivo and had similar biodistribution profiles, with peak tumor accumulation between 6 and 24 h post-injection. In vivo/ex vivo FMT imaging showed 17-34% ID/g Ab uptake by the tumor at 96 h. Overall, this is the first study to characterize the biodistribution of an Ab using eight NIR fluorophores. Our results show that 3-dimensional optical imaging is a valuable technology to understand biodistribution and targeting, but a careful selection of the fluorophore for each Ab is warranted.

Availability, prices and affordability of the World Health Organization's essential medicines for children in Guatemala.

BACKGROUND: Several World Health Organization (WHO) initiatives aim to improve the accessibility of safe and effective medicines for children. A first step in achieving this goal is to obtain a baseline measure of access to essential medicines. The objective of this project was to measure the availability, prices, and affordability of children's medicines in Guatemala. METHODS: An adaption of the standardized methodology developed by the World Health Organization and Health Action International (HAI) was used to conduct a cross sectional survey to collect data on availability and final patient prices of medicines in public and private sector medicine outlets during April and May of 2010. RESULTS: A subset of the public sector, Programa de Accesibilidad a los Medicamentos (PROAM), had the lowest average availability (25%) compared to the private sector (35%). In the private sector, highest and lowest priced medicines were 22.7 and 10.7 times more expensive than their international reference price comparison. Treatments were generally unaffordable, costing as much as 15 days wages for a course of ceftriaxone. CONCLUSIONS: Analysis of the procurement, supply and distribution of specific medicines is needed to determine reasons for lack of availability. Improvements to accessibility could be made by developing an essential medicines list for children and including these medicines in national purchasing lists.

Colorectal cancer screening among Mexican Americans at a community clinic.

BACKGROUND: Mexican Americans tend to under-utilize colorectal cancer (CRC) prevention. Yet little is known about sociocultural factors associated with CRC screening. This study assessed predictors of three primary CRC tests among low-income Mexican Americans. METHODS: From May to December 2003, an availability sample of 287 patients, aged 50 to 89 years, who presented for routine care at a community health center near the U.S.-Mexico border completed surveys on CRC knowledge, awareness, attitudes toward screening, logistic barriers, perceptions of health, locus of control, acculturation, whether their doctor discussed CRC screening, and sociodemographics. Participants also reported whether they had ever had a fecal occult blood test, flexible sigmoidoscopy, or colonoscopy. Logistic regression identified predictors of having had these tests. RESULTS: Overall, 41% reported having ever had any of the three tests; 34.1% had a fecal occult blood test; 6.6%, flexible sigmoidoscopy; and 11.8%, colonoscopy. Few respondents reported any clear knowledge about CRC, and only 41% said their doctor had ever discussed screening with them. Yet "doctor discussed screening" was the only consistent screening predictor across tests. CRC knowledge (p=0.006) and insurance coverage (p=0.009) predicted having had a flexible sigmoidoscopy. Perceptions of general poor health also predicted having had a flexible sigmoidoscopy or a colonoscopy (p=0.04). Being employed marginally predicted whether patient had ever had any of the three tests (p=0.05). CONCLUSIONS: Results show that even those in contact with community medical services exhibit low CRC screening rates. They further suggest that interventions focused on clinical settings are an important first step toward CRC prevention in this community.