2669
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cells. In vivo growth delay assay: 10-week-old, female athymic NCR-nu/nu nude mice bearing A549 tumor xenografts were utilized. Experiments were carried out when the tumor volume was between 200 and 400 mm3. The mice were given by either an i.v. or i.p. injection of ONC 2 hr prior to x-irradiation. DCE-MRI perfusion studies: Tumor perfusion (Ktrans) was monitored after ONC treatment. MR spectroscopy: Lactate level in the tumor tissue was measured by MRS. Non-localized 1H in vivo spectra were acquired using a SelMQC pulse sequence. ONC-induced changes in ATP levels were monitored by non-localized 31P NMR spectroscopy. NIRS perfusion studies: Non-invasive blood flow was assessed by diffuse correlation spectroscopy. Results: ONC increased the radiation response by inhibition of both SLDR and PLDR. In animal studies, ONC significantly increased the radiation-induced tumor growth delay of A549 tumors in vivo. Ktrans values at the rim of tumor regions were temporarily increased at 1.5 h post-injection of ONC (Figure-right). ONC increased tumor blood flow by 40% (at 60 min), measured by a NIRS method (N8). However, perfusion of the corresponding muscle tissues on non tumor-bearing leg of mice was not altered by ONC. In contrast, 20% decrease of lactate level was observed using non-localized MR spectroscopy (N3), caused by the removal of tumor acidic metabolites (Figure-left). ATP levels were also decreased (N3), probably due to ONC-induced inhibition of QO2. Conclusions: ONC may be a new and promising drug for the treatment NSCLC as a radiation enhancer. This investigation suggests important potential clinical uses of ONC. Author Disclosure: I. Lee, None; D.H. Kim, None; U. Sunar, None; S. Magnitsky, None; A.G. Yodh, None; K. Shogen, Alfacell Corporation, A. Employment. 2669 Isoflurane Anesthesia Makes OxyLite More Useful in Oxygen Partial Tension Measurements B. Wen, M. Urano, J. A. O’Donoghue, C. C. Ling Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): The presence of hypoxic tumor cells is critical in cancer therapy. To identify these cells, tissue pO2 can be directly measured. A feature of OxyLite pO2 system is: this allows continuous measurements at a fixed point. It has been shown, however, that tumor pO2 fluctuates substantially in continuous measurements. In those studies, various anesthetics were given by ip injection. We questioned whether those instabilities in readings were related to the type of anesthesia, and tested isoflurane, a gas anesthesia given throughout test period, in continuous measurements. Materials/Methods: The pO2 was continuously measured using OxyLite system in 12 R3327-AT tumors growing in nude mice and in muscle. Animals were anesthetized with 1.2% isoflurane balanced by air (21%) or pure oxygen (100% O2). We also investigated pO2 distributions in various-sized tumors of animals breathing air-balanced isoflurane. Results: In animals breathing air-balanced isoflurane, tumor pO2 readings at fixed positions decreased rapidly in the first 1–5 min but remained stable thereafter. Most measurements showed small fluctuations ( 2 mmHg) during the observation period. Large fluctuations ( 2 mmHg) occurred infrequently at high pO2 values. Data of continuous measurements in muscle of tumor-bearing and non-tumor-bearing animals were similar, and most readings were higher than 40 mmHg. The overall pO2 readings in tumors were substantially higher in animals breathing pure oxygen compared to those in air-breathing animals. Tumors in air-breathing animals showed a range of pO2 values with the majority (53%) of 2.5 mmHg; in contrast, tumors of animals breathing pure oxygen were between 60 –70 mmHg and the percentage of pO2 2.5 mmHg was 15% (p0.001). The measurement in different sized-tumors showed the mean percentages of reading 2.5 mmHg in tumor volume of 100 cm3, 200 cm3 and 800 cm3 were 22 , 53, and 61, respectively; the mean pO2 decreased as tumor volume increased (p0.001), with the largest change from 100 to 200 mm3 of tumor. Conclusions: Our data suggested that the OxyLite system, used with isoflurane anesthesia, gives stable readings and could be a valuable tool in tumor pO2 study. It is also shown that a large fraction of hypoxic tumor cells could be substantially reduced by breathing pure oxygen. Author Disclosure: B. Wen, None; M. Urano, None; J.A. O’Donoghue, None; C.C. Ling, None. 2670 When Tumor Repopulation Starts? The Onset Time of Prostate Cancer During Radiation Therapy M. Gao 1,2 , J. Wang 2 , H. Zhang 2 , A. Sethi 1 , N. Mayr 2 1 Loyola University Chicago, Maywood, IL, 2 The Ohio State University, Columbus, OH Purpose/Objective(s): Tumor repopulation has a significant impact on low-dose-rate brachytherapy (1). As for its effect in external-beam radiotherapy (EBRT), there is an ongoing debate on the onset time of tumor repopulation for prostate cancer. Is it short around 4 weeks as assumed by Wang et al (1) or as long as over 200 days and can be ignored as argued by Fowler et al (2)? The purpose of this study is to estimate the tumor repopulation rate and its onset time for prostate cancer by analyzing published EBRT data. Materials/Methods: The Linear-Quadratic (LQ) model, extended to account for tumor repopulation and onset time (1), was used to analyze the clinical data. A recently published clinical study by Perez et al (3) indicated that prolonged EBRT treatment S581 Proceedings of the 48th Annual ASTRO Meeting
Transcript of 2669
cells. In vivo growth delay assay: 10-week-old, female athymic NCR-nu/nu nude mice bearing A549 tumor xenografts wereutilized. Experiments were carried out when the tumor volume was between 200 and 400 mm3. The mice were given by eitheran i.v. or i.p. injection of ONC 2 hr prior to x-irradiation. DCE-MRI perfusion studies: Tumor perfusion (Ktrans) was monitoredafter ONC treatment. MR spectroscopy: Lactate level in the tumor tissue was measured by MRS. Non-localized 1H in vivospectra were acquired using a SelMQC pulse sequence. ONC-induced changes in ATP levels were monitored by non-localized31P NMR spectroscopy. NIRS perfusion studies: Non-invasive blood flow was assessed by diffuse correlation spectroscopy.
Results: ONC increased the radiation response by inhibition of both SLDR and PLDR. In animal studies, ONC significantlyincreased the radiation-induced tumor growth delay of A549 tumors in vivo. Ktrans values at the rim of tumor regions weretemporarily increased at 1.5 h post-injection of ONC (Figure-right). ONC increased tumor blood flow by �40% (at 60 min),measured by a NIRS method (N�8). However, perfusion of the corresponding muscle tissues on non tumor-bearing leg of micewas not altered by ONC. In contrast, �20% decrease of lactate level was observed using non-localized MR spectroscopy(N�3), caused by the removal of tumor acidic metabolites (Figure-left). ATP levels were also decreased (N�3), probably dueto ONC-induced inhibition of QO2.
Conclusions: ONC may be a new and promising drug for the treatment NSCLC as a radiation enhancer. This investigationsuggests important potential clinical uses of ONC.
Author Disclosure: I. Lee, None; D.H. Kim, None; U. Sunar, None; S. Magnitsky, None; A.G. Yodh, None; K. Shogen, AlfacellCorporation, A. Employment.
2669 Isoflurane Anesthesia Makes OxyLite More Useful in Oxygen Partial Tension Measurements
B. Wen, M. Urano, J. A. O’Donoghue, C. C. Ling
Memorial Sloan-Kettering Cancer Center, New York, NY
Purpose/Objective(s): The presence of hypoxic tumor cells is critical in cancer therapy. To identify these cells, tissue pO2 canbe directly measured. A feature of OxyLite pO2 system is: this allows continuous measurements at a fixed point. It has beenshown, however, that tumor pO2 fluctuates substantially in continuous measurements. In those studies, various anesthetics weregiven by ip injection. We questioned whether those instabilities in readings were related to the type of anesthesia, and testedisoflurane, a gas anesthesia given throughout test period, in continuous measurements.
Materials/Methods: The pO2 was continuously measured using OxyLite system in 12 R3327-AT tumors growing in nude miceand in muscle. Animals were anesthetized with 1.2% isoflurane balanced by air (21%) or pure oxygen (100% O2). We alsoinvestigated pO2 distributions in various-sized tumors of animals breathing air-balanced isoflurane.
Results: In animals breathing air-balanced isoflurane, tumor pO2 readings at fixed positions decreased rapidly in the first 1–5min but remained stable thereafter. Most measurements showed small fluctuations (� � 2 mmHg) during the observationperiod. Large fluctuations (� � 2 mmHg) occurred infrequently at high pO2 values. Data of continuous measurements inmuscle of tumor-bearing and non-tumor-bearing animals were similar, and most readings were higher than 40 mmHg. Theoverall pO2 readings in tumors were substantially higher in animals breathing pure oxygen compared to those in air-breathinganimals. Tumors in air-breathing animals showed a range of pO2 values with the majority (53%) of �2.5 mmHg; in contrast,tumors of animals breathing pure oxygen were between 60–70 mmHg and the percentage of pO2 � 2.5 mmHg was � 15%(p�0.001). The measurement in different sized-tumors showed the mean percentages of reading � 2.5 mmHg in tumor volumeof �100 cm3, �200 cm3 and �800 cm3 were 22 , 53, and 61, respectively; the mean pO2 decreased as tumor volume increased(p�0.001), with the largest change from 100 to 200 mm3 of tumor.
Conclusions: Our data suggested that the OxyLite system, used with isoflurane anesthesia, gives stable readings and could bea valuable tool in tumor pO2 study. It is also shown that a large fraction of hypoxic tumor cells could be substantially reducedby breathing pure oxygen.
Author Disclosure: B. Wen, None; M. Urano, None; J.A. O’Donoghue, None; C.C. Ling, None.
2670 When Tumor Repopulation Starts? The Onset Time of Prostate Cancer During Radiation Therapy
M. Gao1,2, J. Wang2, H. Zhang2, A. Sethi1, N. Mayr2
1Loyola University Chicago, Maywood, IL, 2The Ohio State University, Columbus, OH
Purpose/Objective(s): Tumor repopulation has a significant impact on low-dose-rate brachytherapy (1). As for its effect inexternal-beam radiotherapy (EBRT), there is an ongoing debate on the onset time of tumor repopulation for prostate cancer. Isit short around 4 weeks as assumed by Wang et al (1) or as long as over 200 days and can be ignored as argued by Fowler etal (2)? The purpose of this study is to estimate the tumor repopulation rate and its onset time for prostate cancer by analyzingpublished EBRT data.
Materials/Methods: The Linear-Quadratic (LQ) model, extended to account for tumor repopulation and onset time (1), wasused to analyze the clinical data. A recently published clinical study by Perez et al (3) indicated that prolonged EBRT treatment
S581Proceedings of the 48th Annual ASTRO Meeting
