Determination of Boron-Containing Compounds in Urine and Blood Plasma from Boron Neutron Capture Therapy Patients. The Importance of Using Coupled Techniques

Abstract

The necessity of using coupled techniques to analyze samples from boron neutron capture therapy (BNCT) patients prior to element-specific detection has been demonstrated. BNCT patients were infused with p-boronophenylalanine (BPA)-fructose complex before the therapy started. Urine and blood plasma samples were collected at different times after the start of the BPA administration and were run on a porous graphitic carbon column coupled on-line to an inductively coupled plasma-atomic emission spectrometer (ICP-AES) and an ICP time-of-flight mass spectrometer (TOF-MS). In addition to BPA, a possible metabolite to BPA and some minor boron-containing compounds, eluting close to the front, were also found in the urine and plasma samples. Because only the total concentration of boron has been measured so far in earlier studies, the suspected metabolite could not be detected, and this is the first report indicating its presence in urine and plasma of BNCT patients. The abundance of 10B in urine was about the same for BPA and its possible metabolite (98-99%). The ratio between the possible metabolite and BPA was found to differ in the urine from different patients. Most of the patients had a metabolite concentration of approximately 10 mol % of the BPA content in their urine 5-11 h after the start of the BPA administration. This ratio increased to between 30 and 80% when 24 h had passed. The ratio of metabolite to BPA was found to be lower in the plasma than in the urine samples at comparable time after the start of BPA infusion. Preliminary results from micro-LC-electrospray ionization (ESI)-MS/MS measurements on four urine samples indicate that the metabolite has a higher mass than BPA.

Sample introduction systems for the analysis of liquid microsamples by ICP-AES and ICP-MS

“…When coupled to an ion exchange column, the MCN can be efficiently employed to perform the determination of bromate and bromide in waters through ICP-MS [110] or to speciation studies [52,111]. Porous graphitic columns have also been used in conjunction with a MCN for the determination of boron in urine and blood plasma through ICP-AES and ICP-MS [112]. Because of the low sample consumption rates when working with micronebulizers, it is possible to work with reversed phase liquid chromatography with carbon containing mobile phases.…”

Urinary Proteomics Profiles Are Useful for Detection of Cancer Biomarkers and Changes Induced by Therapeutic Procedures

“…To date, a very limited number of papers have investigated the molecular effects of boron compounds and BNCT. Molecular studies were mainly based on the monitoring of Boron-containing compounds in cell lines [11,12], tissue [13], plasma [14,15], and urine [16,17]. As far as we know, no extensive genomic or transcriptomic studies have been performed to evaluate the changes in the transcription that is induced by this treatment.…”

Evaluation of unnatural cyclic amino acids as boron delivery agents for treatment of melanomas and gliomas

“…Both of these characteristics may enhance the uptake of cis -ABCPC and cis -ABCHC by infiltrating tumor cells in the normal brain. Furthermore, both of these compounds are water soluble and cannot be metabolized, which may further enhance their retention in tumor cells compared to BPA, which is metabolized (Svantesson et al, 2002). Our observations suggest that further pre-clinical studies on enantiomerically pure cis -ABCPC and cis -ABCHC are warranted to optimize their delivery and dosing and to evaluate their toxicity prior to clinical evaluation.…”