at 30 days while mice injected with MnSOD-PL prior to 9.5 Gy had a survival rate of 87% (a significant enhancement ofsurvival (p�0.0402)). Following irradiation to 9.75 Gy, 12.5% of control mice survived to day 30 while mice injected withMnSOD-PL prior to 9.75 Gy had a significantly improved survival rate of 75% (p�0.0016). Mice injected with EUK-134 priorto 9.75 Gy irradiation also had an increased survival rate of 38%.

Conclusions: Pretreatment of mice with either MnSOD-PL or MnSOD mimetic EUK-134 prior to WBI protects frommarrow-lethal irradiation damage.

Author Disclosure: M.W. Epperly, None; Y. Niu, None; J.S. Greenberger, Automated Cell, Inc., F. Consultant/Advisory Board.

2651 Changes in Injury Expression After Graded Volume Irradiation of the Rat Lung

A. Novakova-Jiresova, P. van Luijk, H. van Goor, H. H. Kampinga, R. P. Coppes

University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Purpose/Objective(s): The volume dependency of radiation-induced pulmonary toxicity has been long established. Parameterslike mean lung dose and V20 have been used to predict the normal tissue complication probability (NTCP) of radiotherapyinduced lung injury. Recently however, animal studies1,2 have indicated that irradiation of distinct but equivalent volumes maylead to different responses. The aim of this study was to investigate the dose volume relationships of lung irradiation.

Materials/Methods: Single dose irradiations to three different volume levels (100%, 50% and 25%) were applied andrespiratory dysfunction (increase in breathing rates: BR) was related to morphologic abnormalities at different time points afterradiation.

Results: At large lung volumes (100%) an early (6–12 wks) increase in BR was already evident at relatively low doses (ED50;10.7). At this time point only oedema of the vascular walls and perivascular mononuclear infiltrates were denoted. Thisinflammatory vascular damage (VD) affected both large and small vessels and its severity rose with the dose. Later the VDrecovered in parallel with function. At intermediate volumes (50%), an early BR increase was observed at higher doses (ED50;18.9). Besides the VD already seen after lower doses, now also interstitial inflammation (IF), marked by mononuclearinfiltration of alveolar spaces was seen. At the lower doses (16 Gy) of the 50% irradiations, no increases in BR were seen despitethe fact that there was clear VD in the irradiated areas. This implies that VD only translates into functional deficits if largevolumes are irradiated. At the higher doses after 50% irradiation, the severity of IF increased with time after irradiation andtranslated into more severe function loss. At low volumes (25%), although pathology was more severe, including interstitialedema with patches of collagen deposition, hardly any increase in BR was observed (ED50 � 35 Gy).

Conclusions: In conclusion, the mechanism underlying symptomatic radiation-induced lung injury varies depending on timeand the irradiated volume, with recoverable VD at large volumes/low doses and parenchymal injury at higher doses and lowvolumes. Despite severe local damage (IF and VD) small volumes can be irradiated with rather high doses without functionalconsequences. In contrast, low doses smeared out overlarge volumes, albeit reversible, may already give rise to early and largefunctional problems. This study indicates that mean lung dose and V20 may not reliable to predict NTCP of radiation inducedlung injury.

1) Novakova-Jiresova A, van Luijk P, van Goor H, Kampinga HH, Coppes RP. Pulmonary radiation injury: identification ofrisk factors associated with regional hypersensitivity. Cancer research (2005), 65, 9, 3568–3576.

2) van Luijk P, Novakova-Jiresova A, Faber H, Schippers JM, Kampinga HH, Meertens H, Coppes RP. Damage to the heartenhances early radiation-induced lung function loss. Cancer Research (2005) 65 (15) 6509–6511.

Supported by the Dutch Cancer Society (RuG 2002–2673).

Author Disclosure: A. Novakova-Jiresova, None; P. van Luijk, None; H. van Goor, None; H.H. Kampinga, None; R.P. Coppes,None.

2652 Incorporating Biological Metabolite Information Within Treatment of Prostate Carcinoma and Analysisof Dose Escalation Effect

E. K. Lee1, M. Zaider2

1Georgia Institute of Technology, Atlanta, GA, 2Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): NMR studies have indicated that choline (Cho) is elevated in rapidly growing tissues such as tumors.1H MRS can be used to image the location of tumors within the prostate gland. One differentiates cancer from benign tissueby using the ratio (Cho�Cr)/Cit [Cr�creatine; Cit�citrate] of respective peaks in the MR spectrum. The ratios are calculatedon a spatial grid covering the prostate tissue. A voxel transformation (morphing) algorithm is designed for mapping biologicalpoints of interest from MRS images to US/CT images for target dose-escalation treatment design in implants and in IMRT.Robustness of the algorithm is tested, and plan quality and biological significance are evaluated.

Materials/Methods: Biological information was acquired via a GE Signa 1.5 Tesla MR Scanner. Radiofrequency excitationwas achieved by using a whole body birdcage resonator. The NMR signal was received using a 4 element phased array antennacombined with an expandable MRInnervu endorectal RF probe. Images of the gland were taken. Mapping of metabolites overa 50-mm field of view was performed using chemical shift imaging to encode (6.25x6.25x6.25) mm3 voxels. Images andspectral data were then processed. Peak areas of Cho, Cr and Cit were calculated by numerical integration over the spectralranges corresponding to each metabolite.

The morphing algorithm takes as input the MRS prostate voxels with outlined pockets of high tumor cell proliferation, andUS/CT images of the prostate voxels for treatment. The morphing involves a non-rigid body point matching algorithm andsimulated annealing routines to learn and develop a non-rigid point transformation which maps the MRS voxels onto theUS/CT. The resulting transformation is used to map the MRS-identified tumor pockets onto the US/CT images. Cross validationis performed to gauge robustness. The resulting US/CT images are used for target dose-escalation. Using real patient data,optimal plans are obtained via integer programming. Associated plan quality and tumor control probability (TCP) are comparedto guage the benefit of the biological information.

S572 I. J. Radiation Oncology ● Biology ● Physics Volume 66, Number 3, Supplement, 2006