Computer simulation of speciation of trivalent aluminum, gadolinium and yttrium ions in human blood plasma.

The speciation of Al3+, Gd3+ and Y3+ ions in human plasma has been studied by computer simulation using the program HySS2009. A literature computer model of blood plasma was updated and comprised 9 metals, 43 ligands and over 6100 complexes. To this model critically evaluated data of Al3+, Gd3+ and Y3+ constants with blood plasma ligands have been added. Low molecular mass (LMM) speciation of Al3+ ion strongly depends upon the chosen equilibrium model of the metal - phosphate and metal - citrate systems. The obtained computer simulation of LMM speciation data of Al3+ ion were: AlPO4Cit (40.7%), AlPO4CitOH (22.9%), AlCitOH (19.2%) and AlPO4(OH) (12.7%) (% of total LMM Al species pool); for Gd3+ ion: GdAspCit (30%) and GdCit(OH)2 (20%) (% of total [Gd]) and for Y3+ ion: YCit (48%), Y(CO3)2 (32%) and Y(CO3) (11%) (% of total [Y]). Citrate appears as the important binding and mobilizing ligand for all examined ions, while the dominating species are the ternary ones.

Efficacy and toxicity of radioimmunotherapy with (90)Y-DOTA-peptide-ChL6 for PC3-tumored mice.

BACKGROUND: Radioimmunotherapy (RIT) is a new therapeutic modality capable of systemic delivery of radionuclides specifically to sites of metastatic cancer. The L6 monoclonal antibody has been shown to target prostate cancer in preclinical studies and, along with chimeric L6 (ChL6), has been used for RIT in breast cancer patients. METHODS: Pharmacokinetics, blood counts, body weight, and antitumor activity of RIT with (90)yttrium-((90)Y)-DOTA-peptide-ChL6 (75-260 microCi) were determined in nude mice bearing human prostate cancer (PC3) xenografts. RESULTS: RIT produced durable, dose-dependent antitumor effects with a 100% response rate using 112 microCi and 150 microCi (the maximum tolerated dose) of (90)Y-DOTA-peptide-ChL6. Myelotoxicity was reversible, dose-limiting, and dose-related. RIT was associated with improved survival (P = 0.05). All 5 mice in the 150-microCi group survived the 84-day study period vs. 1/8 (13%) for untreated, tumored control mice. CONCLUSIONS: (90)Y-DOTA-peptide-ChL6 targets PC3 human prostate cancer xenografts in nude mice and has an antitumor effect. These results provide a basis for future RIT trials for patients with metastatic prostate cancer.

Re-evaluating the need for hospitalization following synovectomy using Yttrium-90 silicate.

In 51 patients treated with Yttrium-90 (Y-90) synovectomy for rheumatoid (inflammatory) arthritis (IA) and OA of the knee we found that decreased retained knee activity (RKA) and increased extra-articular activity in lymph nodes and liver are more likely to be found in IA than OA and following bilateral knee injections. Joint inflammation, as assessed by radionuclide blood pool scan but not by SF white cell count, correlates with decreased RKA and increased activity in lymph nodes. Intra-articular steroid had no significant effect on retention or extra-articular uptake. Strict hospital immobilization improves RKA of Y-90 in IA but not in OA. Y-90 synovectomy in OA shows good RKA and low extra-articular uptake. We recommend strict immobilization following Y-90 synovectomy, particularly in IA patients and/or those with high joint blood flow.

Quantitative analysis of trace elements in human blood and plasma by energy dispersive X-ray fluorescence.

A photon excitation, secondary target x-ray fluorescence system was used to measure concentrations of Cu, Zn, Br and Rb in whole blood and plasma of healthy adults. The samples preparation method and calculated limits of detection of the technique are reported. Correlation statistics for elemental concentrations have been determined. Verification of the results for copper was performed using atomic absorption spectrophotometry.