Recycling of homogeneous catalysts could be achieved by using magnetic nanoparticles and solid-phase beads, but nanoparticle-supported catalysis proceeded much faster than its counterpart on resins.

Emulsion polymerization was examined as a novel route for the synthesis of core/shell superparamagnetic nanoparticles consisting of a highly crystalline gamma-Fe2O3 core and a very thin polymeric shell wall. These nanoparticles were used as soluble supports for immobilizing Pd catalysts to promote Suzuki cross-coupling reactions. Recovery of catalysts was facilely achieved by applying a permanent magnet externally. Isolated catalysts were reused for new rounds of reactions without significant loss of their catalytic activity.

Our purpose was to study the safety, distribution, pharmacokinetics, immunogenicity and tumor response of intraperitoneal (IP) 212Pb-TCMC-trastuzumab (TCMC is S-2-(4-isothiocyantobenzl)-1, 4, 7, 10-tetraaza-1, 4, 7, 10=tetra (2-carbamoylmethl) cyclododecane) in patients with HER-2 expressing malignancy. Methods In a standard 3+3 Phase 1 design for dose escalation, 212Pb-TCMC-trastuzumab was delivered IP less than 4 hours after giving 4mg/kg IV trastuzumab to patients with peritoneal carcinomatosis who had failed standard therapies. Results Five dosage levels (7.4, 9.6, 12.6, 16.3, 21.1 MBq/m2) showed minimal toxicity at >1 year for the first group and >4 months for others. The lack of substantial toxicity was consistent with the dosimetry assessments (mean equivalent dose to marrow = 0.18 mSv/MBq). Radiation dosimetry assessment was performed using pharmacokinetics data obtained in the initial cohort (n=3). Limited redistribution of radioactivity out of the peritoneal cavity to circulating blood, which cleared via urinary excretion and no specific uptake in major organs was observed in 24 hours. Maximum serum concentration of the radiolabeled antibody was 22.9% at 24h (decay corrected to injection time) and 500 Bq/mL (decay corrected to collection time). Non-decay corrected cumulative urinary excretion was ≤6% in 24h (2.3 half lives). Dose rate measurements performed at 1m from the patient registered less than 5μSv/hr (using portable detectors) in the latest cohort, significantly less than what is normally observed using nuclear medicine imaging agents. Anti-drug antibody assays performed on serum from the first 4 cohorts were all negative. Conclusions Five dose levels of IP 212Pb-TCMC-trastuzumab treatment of patients with peritoneal carcinomatosis showed little agent related toxicity, consistent with the dosimetry calculations.

Purpose The use of receptor-targeted antibodies conjugated to fluorophores is actively being explored for real-time imaging of disease states, however, the toxicity of the bioconjugate has not been assessed in non-human primates. Procedures To this end, the in vivo toxicity and pharmacokinetics of IRDye800 conjugated to cetuximab (cetuximab-IRDye800; 21 mg/kg; equivalent to 250 mg/m2 human dose) was assessed in male cynomolgus monkeysover15 days following intravenous injection and compared with an unlabeled cetuximab-dosed control group. Results Cetuximab-IRDye800 was well tolerated. There were no infusion reactions, adverse clinical signs, mortality, weight loss, or clinical histopathology findings. The plasma half-life for the cetuximab-IRDye800 and cetuximab groups were equivalent (2.5 days). The total recovered cetuximab-IRDye800 in all tissues at study termination was estimated to be 12% of the total dose. Both cetuximab-IRDye800 and cetuximab groups showed increased QTc after dosing. The QTc for the cetuximab-dosed group returned to baseline by day 15, while the QTc of the cetuximab-IRDye800 remained elevated compared to baseline. Conclusion IRDye800 in low molar ratios does not significantly impact cetuximab half-life or result in organ toxicity. These studies support careful cardiac monitoring (ECG) for human studies using fluorescent dyes.

Fluorescent cross-linked nanoparticles with variable fluorophore loading amounts, locations, and particle sizes were synthesized from sequential one-pot functionalization/cross-linking of block copolymer micelles with amine-terminated dye and cross-linker molecules, via reductive amination and amidation. The fluorescence quantum yield and brightness of these nanoparticles were evaluated by steady-state and dynamic fluorescence methods. The results demonstrate that the quantum yield and brightness of the fluorescent nanoparticles correlated directly with the number of dyes/nanoparticle and the nanoparticle size. A strategy to increase the fluorescence brightness of nanoparticles with fluorescein and near-infrared dyes is proposed.