Folic acid-conjugated europium complexes as luminescent probes for selective targeting of cancer cells.

We report the synthesis of three optical probes (Eu(3+)⊂1, Eu(3+)⊂2, and Eu(3+)⊂3) having a luminescent Eu complex (signaling unit) bonded in different positions to folic acid (FA), the folate receptor (FR) targeting unit. The structures of the two regioisomers Eu(3+)⊂1 and Eu(3+)⊂2 were assigned by mass spectrometric experiments. The optical properties and stability of these probes were assessed in phosphate-buffered saline, cell culture medium, rat serum, and cellular lysate, and results indicated that they are chemically and photophysically stable. Cytotoxicity was studied with ovarian cancer cells having high (SKOV-3), intermediate (OVCAR-3), low (IGROV-1), or null (A2780) expression of FRs. The internalized probe, evaluated in SKOV-3, IGROV-1, and A2780 cells, was in the order Eu(3+)⊂2 > Eu(3+)⊂1 > Eu(3+)⊂3. No internalization was observed for A2780 cells. Such results, together with those obtained in competition experiments of FA versus Eu(3+)⊂2 and FA or Eu(3+)⊂2 versus (3)H-FA, indicate that internalization is receptor-mediated and that Eu(3+)⊂2 shows high selectivity and specificity for FR.

DS86 neutron dose: Monte Carlo analysis for depth profile of 152Eu activity in a large stone sample.

The depth profile of 152Eu activity induced in a large granite stone pillar by Hiroshima atomic bomb neutrons was calculated by a Monte Carlo N-Particle Transport Code (MCNP). The pillar was on the Motoyasu Bridge, located at a distance of 132 m (WSW) from the hypocenter. It was a square column with a horizontal sectional size of 82.5 cm x 82.5 cm and height of 179 cm. Twenty-one cells from the north to south surface at the central height of the column were specified for the calculation and 152Eu activities for each cell were calculated. The incident neutron spectrum was assumed to be the angular fluence data of the Dosimetry System 1986 (DS86). The angular dependence of the spectrum was taken into account by dividing the whole solid angle into twenty-six directions. The calculated depth profile of specific activity did not agree with the measured profile. A discrepancy was found in the absolute values at each depth with a mean multiplication factor of 0.58 and also in the shape of the relative profile. The results indicated that a reassessment of the neutron energy spectrum in DS86 is required for correct dose estimation.

152Eu depth profiles in granite and concrete cores exposed to the Hiroshima atomic bomb.

Two granite and two concrete core samples were obtained within 500 m from the hypocenter of the Hiroshima atomic bomb, and the depth profile of 152Eu was measured to evaluate the incident neutron spectrum. The granite cores were obtained from a pillar of the Motoyasu Bridge located 101 m from the hypocenter and from a granite rock in the Shirakami Shrine (379 m); the concrete cores were obtained from a gate in the Gokoku Shrine (398 m) and from a pillar top of the Hiroshima bank (250 m). The profiles of the specific activities of the cores were measured to a depth of 40 cm from the surface using low background germanium (Ge) spectrometers. According to the measured depth profiles, relaxation lengths of incident neutrons were derived as 13.6 cm for Motoyasu Bridge pillar (granite), 12.2 cm for Shirakami Shrine core (granite), and 9.6 cm for concrete cores of Gokoku Shrine and Hiroshima Bank. In addition, a comparison of the granite cores in Hiroshima showed good agreement with Nagasaki data. Present results indicates that the depth profile of 152Eu reflects incident neutrons not so high but in the epithermal region.