Recurrent prostate cancer presents a challenge to conventional treatment, particularly so to address
micrometastatic and small-volume disease. Use of a-radionuclide therapy is considered as a highly effective
treatment in such applications due to the shorter range and exquisite cytotoxicity of a-particles as compared
with b-particles. 213Bi is considered an a-emitter with high clinical potential, due to its short half-life (45.6
minutes) being well matched for use in peptide-receptor radionuclide a-therapy; however, there is limited
knowledge available within this context of use. In this study, two novel 213Bi-labeled peptides, DOTA-PEG4-
bombesin (DOTA-PESIN) and DO3A-CH2CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA), were compared
with 177Lu (b-emitter)-labeled DOTA-PESIN in a human androgen-independent prostate carcinoma
xenograft model (PC-3 tumor). Animals were injected with 177Lu-DOTA-PESIN, 213Bi-DOTA-PESIN, or 213Bi-
AMBA to determine the maximum tolerated dose (MTD), biodistribution, and dosimetry of each agent; controls
were left untreated or were given nonradioactive 175Lu-DOTA-PESIN. The MTD of 213Bi-DOTA-PESIN and 213Bi-
AMBA was 25 MBq (0.68 mCi) whereas 177Lu-DOTA-PESIN showed an MTD of 112 MBq (3 mCi). At these dose
levels, 213Bi-DOTA-PESIN and 213Bi-AMBA were significantly more effective than 177Lu-DOTA-PESIN. At the
same time, 177Lu-DOTA-PESIN showed minimal, 213Bi-DOTA-PESIN slight, and 213Bi-AMBA marked kidney
damage 20 to 30 weeks posttreatment. These preclinical data indicate that a-therapy with 213Bi-DOTA-PESIN or
213Bi-AMBA is more efficacious than b-therapy. Furthermore, 213Bi-DOTA-PESIN has a better safety profile than
213Bi-AMBA, and represents a possible new approach for use in peptide-receptor radionuclide a-therapy treating recurrent prostate cancer.
WILD D.;
FRISCHKNECHT M.;
ZHANG H.;
MORGENSTERN Alfred;
BRUCHERTSEIFER Frank;
BOISCLAIR J.;
PROVENCHER-BOLLIGER A.;
REUBI Jean-Claude;
MAECKE H. R.;
2011-10-20
AMER ASSOC CANCER RESEARCH
JRC54279
0008-5472,
http://cancerres.aacrjournals.org/content/71/3/1009.full.pdf,
html,
https://publications.jrc.ec.europa.eu/repository/handle/JRC54279,
10.1158/0008-5472.CAN-10-1186,
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