Control antibody-coupled NP did not accumulate in lung (<10% ID/g) but accumulated in liver and spleen. Images from microSPECT/CT and autoradiography studies of the targeted NP document this specific uptake and demonstrate uniform distribution in lung with minor accumulation in liver and spleen. Within a few hours, a large fraction of lung-targeted NP redistributed to spleen and liver or was excreted. We hypothesized that NP attract phagocytic
cells that engulfed and removed them from circulation. This was confirmed by comparing biodistribution of targeted NP in normal mice versus those depleted of phagocytic cells. in mice treated with clodronate liposomes, accumulation of NP in liver was reduced by fivefold, while accumulation in lung at 1 h was enhanced by similar to ICG-001 research buy 50%. By 24 h, loss of the targeted NP from lung was inhibited by several-fold, while accumulation in liver and Bindarit cost spleen remained constant. Thus, the treated mice had a much larger accumulation and retention of the NP at the target site and a decrease in dose to other organs except spleen.
Conclusion: Nanoparticles composed of CdTe, labeled with Te-125m and capped with ZnS, can be targeted with MAb to sites in the lumen of lung
vasculature. In clodronate-treated mice, which have a temporary depletion of phagocytic cells, accumulation in liver was reduced dramatically, whereas that in spleen was not. The targeting to lung was several-fold more efficient in clodronate-treated mice due to larger initial accumulation and better retention of the MAb-targeted NP at that site. This model system indicates that targeting Urease of NP preparations is a competition between the effectiveness
of the targeting agent and the natural tendency for RE uptake of the particles. Temporary inhibition of the RE system may enhance the usefulness of NP for drug and radioisotope delivery. (C) 2008 Elsevier Inc. All rights reserved.”
“Introduction: To complement recent studies using the high-affinity (11)C-labeled phosphodiesterase-4 (PDE4) inhibitor (R)-rolipram and the less active enantiomer (S)-[(11)C]rolipram for in vivo quantification of PDE4 levels, we evaluated the presence of radiolabeled metabolites and their potential binding to PDE4 in the rat plasma, brain, heart, pancreas, skeletal muscle and brown adipose tissue.
Methods: A reverse-phase capture and analytical HPLC column-switch method was used to detect (R)-[(11)C]rolipram, (S)-[(11)C]rolipram and their radiolabeled metabolites in rat plasma and tissue extracts. The relative proportion of PDE4-specific binding of the radiotracers; and their labeled metabolites was analyzed following co-injections with a saturating dose of unlabeled (R)-rolipram at 45 min post-tracer injection in tissue extracts.
Results: Radiolabeled metabolites were found in the plasma (72-75% of total radioactive signal), and in the heart, skeletal muscle, pancreas and brown adipose tissue (44-52%), but not in the brain.