Boron-gadolinium binary system as a magnetic resonance imaging boron carrier*

The evaluation of the Gd-carborane DTPA complex as a magnetic resonance imaging (MRI) and boron carrier agent was carried out in vivo. The MRI revealed that the Gd-carborane DTPA was metabolized slower in the body in comparison with Gd-DTPA. In order to improve and optimize efficient NCT treatment, it is necessary to follow the distribution of a carrier in the body in real time. For this purpose, positron emission tomography (PET) using fluorine18-labeled fluoroboronophenylalanine (18F-BPA) has recently been evaluated in humans. Magnetic resonance imaging (MRI) can also be used to follow the kinetics of the boron compounds. It is indeed a noninvasive tool, and contrast can be modified by the injection of extrinsic contrast agents. Although boron-11 MRI has been studied for this purpose, the actual nucleus for neutron capture reaction is boron-10, and, therefore, the administration of extra amounts of boron-11 compound (which does not undergo the nucleic reaction) is needed for MRI. The Gd-DTPA complex 1, which is commercially available under the trade name of “Magnevist” and is used as an MRI contrast medium, is paramagnetic, therefore, its effect on the contrast of the images can be best seen on T1-weighted images with short repetition times. The effect is caused by the gadolinium ion in the center, which induces an enhancement of T1 relaxation. It has been observed that the blood–brain barrier of brain tumor is disrupted, and that the complex 1 can pass through this disrupted barrier and enter into the tumor tissue. Furthermore, gadolinium-157 has a higher thermal neutron capture cross-section (255 000 b) in comparison with that of boron-10 (3838 b). It occurred to us that a combination of gadolinium-157 and boron-10 might prove effective not only as an MRI but also as a neutron capture therapy. We have recently succeeded the synthesis of the Gd-DTPA complex 2 which contains a carborane unit attached via a palladium-catalyzed C–C bond formation reaction [1]. Herein, we report in vivo evaluation of the complex 2 using tumor-bearing rats by means of MRI, ICP, and α-autoradiographic methods. *Lecture presented at the XIth International Meeting on Boron Chemistry (IMEBORON XI), Moscow, Russia, 28 July–2 August 2002. Other presentations are published in this issue, pp. 1157–1355. MRI OF RAT TUMOR WITH Gd-CARBORANE COMPLEX 2 [2] Figure 1a shows the sagittal T1-weighted MR image of a rat with a tumor implanted on its back before injection of any compounds, and Figs. 1b–d show the images at 4 min 23 s (b), 11 min 32 s (c), and 50 min 54 s (d) after injection of 2. The signal intensity of kidney, liver, bladder, heart, and tumor on the images is calculated by the Philips software, and the intensity of the images vs. time is plotted in Figs. 2a and 2b. The signal intensity is plotted as the ordinate, and the time after injection is plotted on the horizontal axis. Although the dynamic change of the intensity in each tissue can be seen from these images, the comparison of the intensity among the tissues is not possible since the signal intensity strongly depends on the distance between the tissue and the surface coil. The contrast enhancement was observed in the center of tissue, which is indicated by the circle in Figs. 1c and 1d. The signal intensity of tumor tissues also increased rapidly after injection of 2 and decreased slowly (Fig. 2b). The signal intensity of kidney rapidly increased after injection of the compound and remained constant throughout the experiment period, whereas, that of liver, heart, and tumor rapidly increased after injection and decreased slowly (Fig. 2). Further, the contrast enhancement was also observed in the bladder at 50 min after injection, which is indicated by the arrow in Fig. 1d. The signal intensity of bladder increased at 45 min after injection (Fig. 2a). On the other hand, the signal intensity of all tissues increased rapidly after injection of normal Gd-DTPA 1 and decreased rapidly after 10 min (Fig. 3). The signal intensity of bladder also increased rapidly after injection. Y. YAMAMOTO © 2003 IUPAC, Pure and Applied Chemistry 75, 1343–1348 1344