Mandeep K. Khela

The Biodistribution and Radiation Dosimetry of the Arg-Gly-Asp Peptide 18F-AH111585 in Healthy Volunteers

We report the safety, biodistribution, and internal radiation dosimetry of a new PET tracer, 18F-AH111585, a peptide with a high affinity for the αvβ3 integrin receptor involved in angiogenesis. Methods: PET scans of 8 healthy volunteers were acquired at time points up to 4 h after a bolus injection of 18F-AH111585. 18F activity in whole blood and plasma and excreted urine were measured up to 4 h after injection. In vivo 18F activities in up to 12 source regions were determined from quantitative analysis of the images. The cumulated activities subsequently calculated were then used to determine the internal radiation dosimetry, including the effective dose. Results: Injection of 18F-AH111585 was well tolerated in all subjects, with no serious or drug-related adverse events reported. The main route of 18F excretion was renal (37%), and the 3 highest initial uptakes were by liver (15%); combined walls of the small, upper large, and lower large intestines (11%); and kidneys (9%). The 3 highest absorbed doses were received by the urinary bladder wall (124 μGy/MBq), kidneys (102 μGy/MBq), and cardiac wall (59 μGy/MBq). The effective dose was 26 μGy/MBq. Conclusion: 18F-AH111585 is a safe PET tracer with a dosimetry profile comparable to other common 18F PET tracers.

A new concept in colonic drug targeting: a combined pH‐responsive and bacterially‐triggered drug delivery technology

Background  Current approaches to colonic drug delivery exploit one of two main physiological characteristics: the pH change or increase in bacterial numbers along the gastrointestinal tract. Here, we describe a new concept in targeted delivery, which combines these triggers to improve colonic delivery.

Impact of formulation excipients on human intestinal transit.

The accelerating effect of polyethylene glycol 400 on small intestinal transit has been previously reported. The aim of this study was to investigate the influence of other solubility‐enhancing excipient, propylene glycol, D‐α‐tocopheryl‐polyethylene glycol‐1000 succinate (VitE‐TPGS) and Capmul MCM, on human intestinal transit. A 5‐g dose of each excipient was administered to seven healthy male subjects. Propylene glycol and VitE‐TPGS were administered dissolved in 150 mL water. Capmul MCM was administered in the form of four 000 hard gelatin capsules to mask its taste and then given with 150 mL water. On a separate occasion, 150 mL water was administered as the control. Each formulation was radiolabelled with technetium‐99 m to follow its transit using a gamma camera. The mean small intestinal transit times were 234, 207, 241 and 209 min for the control, propylene glycol, VitE‐TPGS and Capmul MCM treatments, respectively. Although there were differences in the small intestinal transit times for the excipients investigated compared with the control, none of the results were statistically significant. Unlike polyethylene glycol 400 at the same dose of 5g, the excipients tested (propylene glycol, VitE‐TPGS and Capmul MCM) had little or no impact on small intestinal transit.