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Radiation dosimetry of 131I-chlorotoxin
for targeted radiotherapy in glioma-bearing mice
Sui Shen, M. B. Khazaeli,
G. Yancey Gillespie and Vernon L. Alvarez
Department
of Radiation Oncology, Birmingham, AL, USA [S.S., M.B.K.]. Department
of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL,
USA [G.Y.G.]. TransMolecular, Inc., Birmingham, Alabama, USA [V.L.A.].
Department of Radiation Oncology, University of Alabama at Birmingham,
619 19th South Street South, WTI 124, Birmingham, AL 35249, USA
[S.S.].
Correspondence to: Sui Shen, Email: ssh-en@uabmc.edu,
Phone: +1-205-975-0409, Fax: +1-205-975-2546.
Chlorotoxin, or TM-601, is a peptide
derived from the venom of the scorpion Leiurus Quinquestriatus
that specifically binds to malignant brain tumors, but not to normal
tissues.
Targeted radiotherapy using 131I-Chlorotoxin is promising
for post-surgery treatment of brain tumors.
This study reports dosimetry results of 131I-Chlorotoxin in
athymic nude mice with intracranially implanted human glioma
xenografts and projected radiation doses in patients receiving 370 MBq
of 131I-Chlorotoxin.
125I/131I-Chlorotoxin were injected into the
right brain where D54 MG xenografts were implanted.
Mice were sacrificed 24–96 h later.
The blood, normal organs, and tumors were weighed and counted to
determine 131I-Chlorotoxin concentration.
The radiation dose from 131I was calculated based on
non-penetrating radiation in the mouse model.
Assuming similar tissue uptake in mice and patients, radiation doses
for patients were extrapolated.
Distributions of 125I/131I-Chlorotoxin were only
significant in tumor, stomach, kidneys, and brain (injection site),
reflecting non-specific uptake of Chlorotoxin in normal tissues.
Mean radiation dose (cGy/37 kBq)
was 58.2 for tumor, 17.9 for brains, 1.8 for marrow, 27.1 for stomach,
16.0 for kidneys in mice.
For intracranial injection of 370 MBq
131I-Chlorotoxin in patients, extrapolated patient dose
(cGy) was 70 for brains, 6 for marrow, 35 for stomach, 60 to kidneys,
227 to tumor, suggesting that 3.7 GBq
of 131I-Chlorotoxin can be safely administrated to
patients.
These promising results demonstrated potential in improving patient
survival using this novel targeting agent.
Keywords:
Chlorotoxin - glioma - radiation
dosimetry - target radiotherapy - TM-601
© Springer 2005
Source: http://springerlink.metapress.com/openurl.asp?genre=article&eissn=1573-7373&volume=71&issue=2&spage=113
DOI: http://dx.doi.org/10.1007/s11060-004-0890-4
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