Relationship Between pO2 and Response to Radioantibody
Immunotheraphy
1O’Hara, J., 2 Blumenthal, R., 1Wilmot, C., and 1Swartz, HM
1EPR Center for the Study of Viable Biological Systems, Dartmouth Medical
School,
Hanover, NH 03755 – USA
2Garden State Cancer Center, Belleville, NJ – USA
INTRODUCTION: Radioantibody immunotherapy (RAIT) is a promising
treatment modality but the
effectiveness of this targeted radiation for the same type of tumor varies
among individuals.
Since RAIT is an oxygen dependent treatment, we postulated that the
variability in
responsiveness of tumors to a fixed dose of radioimmunotherapy (RAIT) might
be related to the
tumor pO2 at the time that RAIT was administered or to the development of
tumor hypoxia post-
RAIT. This information could be important for ascertaining the likelihood of
the tumor
responding to additional doses that would be administered as part of a
multiple dose scheme.
Additionally, it may help identify a window of opportunity when the
surviving tumor regions
would be responsive to a second therapeutic modality, such as hypoxic
cytotoxins.
METHOD: We measured baseline tumor pO2 of CALU-3 non-small cell lung
carcinoma
xenografts using EPR oximetry. We then serially measured tumor volume and
tumor pO2 after
treatment with a therapeutic dose of RAIT (240 mCi dose of
I-131-RS-7-anti-EGP-1) by serial
measurements of tumor pO2 for 50-80 days post RAIT.
RESULTS: Following a dose of RAIT, there was an initial spike in pO2
(doubling on day 3)
followed by a fall below initial levels from day 14 to day 49, before
beginning to climb again.
Thus, defined times may exist when the tumor is more or less radiosensitive
after RAIT. Our
results also showed a correlation of tumor growth rate with tumor at the
time of RAIT dosing.
There appears to be relationship between the initial level of oxygen and the
response to the
RAIT. Those tumors that had higher levels of pO2 at the time of treatment
appeared to respond
better to the treatment. This may reflect a direct effect of the level of
oxygen and/or is an
indicator of better perfusion leading to better delivery of the RAIT.
These results illustrate the potential value of serial measurements of pO2
for characterizing
tumors for purposes of both monitoring the effectiveness of treatments and
for providing
information that would enable therapy to be individualized to obtain maximum
effectiveness
with minimum side effects.
Figure: Effect of
Radioimmunotherapy (RAIT) on
human xenograft lung tumors, CALU-3 (A) tumor volume (B)
tumor pO2. Panel A groups the tumors according to the day they
reached 250 mm3. Panel B is the pO2 over time for each of
the groups in panel A. The two intermediate groups were pooled for panel B.
REFERENCE:
J.A. O'Hara, R.D. Blumenthal, O.Y. Grinberg, E. Demidenko, S. Grinberg, C.M.
Wilmot, A.M. Taylor, D.M.
Goldenberg and H.M. Swartz, “Response to Radioimmunotherapy Correlates with
Tumor pO2 Measured by
EPR Oximetry in Human Tumor Xenografts,” Radiat. Res. 155:466-473 (2001).