Fig. 4.

Alpha particles promote a feed-forward oncoaddictive effect that promulgates lethality. a The increasing uptake of [²²⁵Ac]hu11B6 is shown as %IA/g (red-filled circles with a blue connecting line) in LNCaP-AR tumor at four time-points after IV administration. This escalating rate of drug accumulation in tumor is noted by the linear regression fit (solid red line) with slope = 0.037 ± 0.001 %IA/g/h. b Therapeutic efficacy of a single administration of [²²⁵Ac]hu11B6 is evidenced by the decreasing tumor volumes compared with vehicle-treated controls where the trajectory of untreated tumor volumes steadily increase with time. c These data report the measured AR-driven luciferase bioluminescence signal (photons/s/mm²/sr) vs. time in the treated and control animals. Note that while the alpha irradiated tumor volume decreases (see panel 4B) with time while AR-driven BLI signal increases. These data show upregulation of AR expression as a consequence of alpha irradiation with [²²⁵Ac]hu11B6. d RT-PCR analysis of AR and AR-driven genes in tumor tissues collected from [²²⁵Ac]hu11B6- and vehicle-treated mice at 400 h. The fold-change in tumor gene activity of treated animals normalized to non-treated tumors shows increased expression of AR, KLK2, and KLK3, but not FOLH1