title: A Systematic Comparison of 18F-C-SNAT to Established Radiotracer Imaging Agents for the Detection of Tumor Response to Treatment.
abstract: OBJECTIVE
  An early readout of tumor response to therapy through measurement of drug or radiation-induced cell death may provide important prognostic indications and improved patient management. It has been shown that the uptake of (18)F-C-SNAT can be used to detect early response to therapy in tumors by positron emission tomography (PET) via a mechanism of caspase-3-triggered nanoaggregation.
  
  
  METHODS
  Here, we compared the preclinical utility of (18)F-C-SNAT for the detection of drug-induced cell death to clinically evaluated radiotracers, (18)F-FDG, (99m)Tc-Annexin V, and (18)F-ML-10 in tumor cells in culture, and in tumor-bearing mice in vivo.
  
  
  RESULTS
  In drug-treated lymphoma cells, (18)F-FDG, (99m)Tc-Annexin V, and (18)F-C-SNAT cell-associated radioactivity correlated well to levels of cell death (R(2) > 0.8; P < 0.001), with no correlation measured for (18)F-ML-10 (R(2) = 0.05; P > 0.05). A similar pattern of response was observed in two human NSCLC cell lines following carboplatin treatment. EL-4 tumor uptake of (99m)Tc-Annexin V and (18)F-C-SNAT were increased 1.4- and 2.1-fold, respectively, in drug-treated versus naïve control animals (P < 0.05), although (99m)Tc-Annexin V binding did not correlate to ex vivo TUNEL staining of tissue sections. A differential response was not observed with either (18)F-FDG or (18)F-ML-10.
  
  
  CONCLUSIONS
  We have demonstrated here that (18)F-C-SNAT can sensitively detect drug-induced cell death in murine lymphoma and human NSCLC. Despite favorable image contrast obtained with (18)F-C-SNAT, the development of next-generation derivatives, using the same novel and promising uptake mechanism, but displaying improved biodistribution profiles, are warranted for maximum clinical utility.
authors.affiliation: Department of Radiology, Stanford University, Stanford, California. sgambhir@stanford.edu.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Witney
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Aileen
authors.initials: A
authors.lastname: Hoehne
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Reeves
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Ohad
authors.initials: O
authors.lastname: Ilovich
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Namavari
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Rao
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D052160:Benzothiazoles / Q000378:metabolism; D001682:Biological Availability; D016923:Cell Death; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis* / Q000628:therapy; D009842:Oligopeptides / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; C000602832:C-SNAT compound; D009842:Oligopeptides; D019275:Radiopharmaceuticals