title: Comparison of methods for evaluating radiolabelled Annexin A5 uptake in pre-clinical PET oncological studies.
abstract: OBJECTIVE
  The uptakes of radiolabel led AnnexinA5 (AnxA5) and a size-matched control protein in experimental tumours were evaluated by kinetic analyses and compared with standard uptake values (SUVs) to investigate whether the method of analysis may impact on the conclusions that can be drawn.
  
  
  METHODS
  PET scans of the (11)C-labelled proteins performed in untreated and doxorubicin-treated mice with head and neck carcinoma xenografts were retrospectively analysed. The appropriateness of using the Logan graphical analyses for reversibly binding radiotracers in these models was evaluated and confirmed. Distribution volume ratios (DVRs) of the regions of interest to reference muscle tissue were compared to those based on the image-derived input function from arterial blood. SUVs were calculated in the same individuals.
  
  
  RESULTS
  DVRs based on reference muscle tissue gave results similar to those based on the arterial blood and may be preferred since they are simpler to calculate. In the inter-group comparisons of baseline versus chemotherapy treatment or AnxA5 versus control protein, differences in DVR quantifications had a 20- to 40-fold higher statistical significance than differences in SUVs. As quantified using the control protein, the amount of free ligand in the vascular space of tumours may be large due to enhanced permeability and retention (EPR) contributions at baseline and affected during treatment, which has implications for quantifications of the specifically bound radioligand.
  
  
  CONCLUSIONS
  These results demonstrate that the quantification method as well as the controls used can be important for interpreting the uptake in tumours of the medium-sized protein ligand AnxA5 and its use in monitoring the effects of therapy on cell death in the tumours.
  
  
  CONCLUSIONS
  These results provide additional support for the recognition that more detailed investigations on the effects of the tumour microenvironment on the targeting capability of imaging radiopharmaceuticals are needed.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Grafström
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; PET Radiochemistry, Neuroradiology Department, R3:00, Karolinska University Hospital Solna, Stockholm, Sweden. Electronic address: sharon.stone-elander@karolinska.se.
authors.forename: Sharon
authors.initials: S
authors.lastname: Stone-Elander
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000032:analysis*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D016513:Mice, SCID; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals
chemical_list: D017304:Annexin A5; D000903:Antibiotics, Antineoplastic; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D004317:Doxorubicin
keywords: AnnexinA5; Distribution volume ratio; Enhanced permeability and retention effects; Logan method; Positron emission tomography