Dodecaborate Conjugates Targeting Tumor Cell Overexpressing Translocator Protein for Boron Neutron Capture Therapy.

We developed novel closo-dodecaborate ([B12H11]2-) anion-containing translocator protein (TSPO) ligand as a boron carrier for boron neutron capture therapy. This compound shows high water solubility and can deliver boron to TSPO highly expressed in breast cancer cells. We describe the synthesis and in vitro evaluation of a dodecaborate-based pyrazolopyrimidine.

Detection of boronic acid derivatives in cells using a fluorescent sensor.

The detection of boron-containing compounds requires very expensive facilities and/or tedious sample pretreatments. In an effort to develop a convenient detection method for boronic acid derivatives, boron chelating-ligands were synthesized for use as fluorescent sensors. In this paper, the synthesis and properties of fluorescent sensors for boronic acid derivatives are reported.

A physiologic model for recirculation water correction in CMRO2 assessment with 15O2 inhalation PET.

Cerebral metabolic rate of oxygen (CMRO(2)) can be assessed quantitatively using (15)O(2) and positron emission tomography. Determining the arterial input function is considered critical with regards to the separation of the metabolic product of (15)O(2) (RW) from a measured whole blood. A mathematical formula based on physiologic model has been proposed to predict RW. This study was intended to verify the adequacy of that model and a simplified procedure applying that model for wide range of species and physiologic conditions. The formula consists of four parameters, including of a production rate of RW (k) corresponding to the total body oxidative metabolism (BMRO(2)). Experiments were performed on 6 monkeys, 3 pigs, 12 rats, and 231 clinical patients, among which the monkeys were studied at varied physiologic conditions. The formula reproduced the observed RW. Greater k values were observed in smaller animals, whereas other parameters did not differ amongst species. The simulation showed CMRO(2) sensitive only to k, but not to others, suggesting that validity of determination of only k from a single blood sample. Also, k was correlated with BMRO(2), suggesting that k can be determined from BMRO(2). The present model and simplified procedure can be used to assess CMRO(2) for a wide range of conditions and species.

Rapid quantitative measurement of CMRO(2) and CBF by dual administration of (15)O-labeled oxygen and water during a single PET scan-a validation study and error analysis in anesthetized monkeys.

Cerebral blood flow (CBF) and rate of oxygen metabolism (CMRO(2)) may be quantified using positron emission tomography (PET) with (15)O-tracers, but the conventional three-step technique requires a relatively long study period, attributed to the need for separate acquisition for each of (15)O(2), H(2)(15)O, and C(15)O tracers, which makes the multiple measurements at different physiologic conditions difficult. In this study, we present a novel, faster technique that provides a pixel-by-pixel calculation of CBF and CMRO(2) from a single PET acquisition with a sequential administration of (15)O(2) and H(2)(15)O. Experiments were performed on six anesthetized monkeys to validate this technique. The global CBF, oxygen extraction fraction (OEF), and CMRO(2) obtained by the present technique at rest were not significantly different from those obtained with three-step method. The global OEF (gOEF) also agreed with that determined by simultaneous arterio-sinus blood sampling (gOEF(A-V)) for a physiologically wide range when changing the arterial PaCO(2) (gOEF=1.03gOEF(A-V)+0.01, P<0.001). The regional values, as well as the image quality were identical between the present technique and three-step method for CBF, OEF, and CMRO(2). In addition, a simulation study showed that error sensitivity of the present technique to delay or dispersion of the input function, and the error in the partition coefficient was equivalent to that observed for three-step method. Error sensitivity to cerebral blood volume (CBV) was also identical to that in the three-step and reasonably small, suggesting that a single CBV assessment is sufficient for repeated measures of CBF/CMRO(2). These results show that this fast technique has an ability for accurate assessment of CBF/CMRO(2) and also allows multiple assessment at different physiologic conditions.