PARENT SESSION
1:30 PM to 3:30 PM
Wednesday, April 24, 2002
Poster Session 30 Bystander Effects
Room: Nevada Exhibition Center

(P35-355) Bystander Effect Produced by Radiolabeled Tumor Cells In Vivo.

Kassis, Amin^*,1, Xue, Lanny¹, Butler, Nicholas¹, Makrigiorgos, Mike², Adelstein, James¹, ¹ Department of Radiology, Boston, MA² Department of Radiation Oncology, Boston, MA

ABSTRACT-
The bystander effect, originating from cells irradiated in vitro, describes biologic response(s) of surrounding cells not directly targeted by a radiation insult. To overcome the limitations of in-vitro tissue culture models and to determine whether a bystander effect that is initiated by radionuclide decay can be demonstrated in vivo, we investigated the ability of 5-[¹²⁵I]iodo-2'-deoxyuridine (¹²⁵IUdR)-labeled tumor cells to exert a damaging effect on neighboring unlabeled tumor cells growing subcutaneously in nude mice. We found that the co-injection of human colon LS174T adenocarcinoma cells prelabeled with lethal doses of DNA-incorporated ¹²⁵IUdR and unlabeled LS174T cells (1:1, 0.2:1, and 0.1:1) elicits distinct inhibitory effects on the growth of these subcutaneous tumors and that the potency of the effect correlates with the ratio of ¹²⁵IUdR-labeled cells to unlabeled cells. Since (i) the ¹²⁵I present within the cells is DNA-bound, (ii) ~99% of the electrons emitted by the decaying ¹²⁵I atoms have a range of <0.5 m, and (iii) the radiation dose deposited by the radiolabeled cells into the growing tumor is 1/10^th to 1/100^th that needed to inhibit tumor growth (<100 cGy), we conclude that the results obtained are a consequence of a bystander effect that seems to be generated in vivo by factor(s) present within and/or released from the ¹²⁵IUdR-labeled cells. These in-vivo findings call for a re-evaluation of the dosimetric approaches currently used for estimating the radiation dose and risks to patients undergoing routine diagnostic nuclear medical procedures. In addition, they significantly impact the current dogma for assessing the therapeutic potential of internally administered therapeutic radionuclides.

KEYWORDS: iodine-125, Auger electrons, bystander effect, risk assessment