title: Predictive models for regional hepatic function based on 99mTc-IDA SPECT and local radiation dose for physiologic adaptive radiation therapy.
abstract: OBJECTIVE
  High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT.
  
  
  METHODS
  Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF) images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose-response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT.
  
  
  RESULTS
  The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=-0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001).
  
  
  CONCLUSIONS
  99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA. hesheng@umich.edu
authors.forename: Hesheng
authors.initials: H
authors.lastname: Wang
authors.forename: Mary
authors.initials: M
authors.lastname: Feng
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Frey
authors.forename: Randall K
authors.initials: RK
authors.lastname: Ten Haken
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy; D018281:Cholangiocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy; D004396:Coloring Agents / Q000493:pharmacokinetics*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006207:Half-Life; D006801:Humans; D007098:Imino Acids; D007208:Indocyanine Green / Q000493:pharmacokinetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000528:radiation effects; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging / Q000378:metabolism; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D011832:Radiation Injuries / Q000517:prevention & control; D019275:Radiopharmaceuticals; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D019784:Technetium Tc 99m Diethyl-iminodiacetic Acid; D014057:Tomography, X-Ray Computed
chemical_list: D004396:Coloring Agents; D007098:Imino Acids; D019275:Radiopharmaceuticals; D019784:Technetium Tc 99m Diethyl-iminodiacetic Acid; D007208:Indocyanine Green; C008109:iminodiacetic acid