TY - JOUR
T1 - A comparison of the imaging characteristics and microregional distribution of 4 hypoxia PET tracers
AU - Carlin, Sean
AU - Zhang, Hanwen
AU - Reese, Megan
AU - Ramos, Nicholas N.
AU - Chen, Qing
AU - Ricketts, Sally Ann
PY - 2014/3/1
Y1 - 2014/3/1
N2 - We compared the imaging characteristics and hypoxia selectivity of 4 hypoxia PET radiotracers (18F-fluoromisonidazole [ 18F-FMISO], 18Fflortanidazole [18F-HX4], 18F-fluoroazomycin arabinoside [18F-FAZA], and 64Cu-diacetyl-bis(N4-methylsemicarbazone) [64Cu-ATSM]) in a single murine xenograft tumor model condition using small-animal PET imaging and combined ex vivo autoradiography and fluorescence immunohistochemistry. Methods: Nude mice bearing SQ20b xenograft tumors were administered 1 of 4 hypoxia PET tracers and images acquired 80-90 min after injection. Frozen sections from excised tumors were then evaluated for tracer distribution using digital autoradiography and compared with histologic markers of tumor hypoxia (pimonidazole, carbonic anydrase 9 [CA9]) and vascular perfusion (Hoechst 33342). Results: The highest tumor uptake was observed with 64Cu-ATSM (maximum standardized uptake values [SUVmax], 1.26 ± 0.13) and the lowest with 18F-FAZA (SUVmax, 0.41 ± 0.24). 18F-FMISO and 18F-HX4 had similar intermediate tumor uptake (SUVmax, 0.76 ± 0.38 and 0.65 ± 0.19, respectively). Digital autoradiographs of hypoxia tracer distributionwere compared pixel by pixelwith images of immunohistochemistry stains. The fluorinated nitroimidazoles all showed radiotracer uptake increasing with pimonidazole and CA9 staining. 64Cu-ATSM showed the opposite pattern, with highest radiotracer uptake observed in regions with the lowest pimonidazole andCA9staining. Conclusion: The fluorinatednitroimidazoles showed similar tumordistributionswhencomparedwithimmunohistochemistry markers of hypoxia. Variations in tumor standardized uptake value and normal tissue distribution may determine the most appropriate clinical setting for each tracer. 64Cu-ATSM showed the highest tumor accumulation and little renal clearance. However, the lack of correlation between 64Cu-ATSM distribution and immunohistochemistry hypoxia markers casts some doubt on the hypoxia selectivity of 64Cu-ATSM.
AB - We compared the imaging characteristics and hypoxia selectivity of 4 hypoxia PET radiotracers (18F-fluoromisonidazole [ 18F-FMISO], 18Fflortanidazole [18F-HX4], 18F-fluoroazomycin arabinoside [18F-FAZA], and 64Cu-diacetyl-bis(N4-methylsemicarbazone) [64Cu-ATSM]) in a single murine xenograft tumor model condition using small-animal PET imaging and combined ex vivo autoradiography and fluorescence immunohistochemistry. Methods: Nude mice bearing SQ20b xenograft tumors were administered 1 of 4 hypoxia PET tracers and images acquired 80-90 min after injection. Frozen sections from excised tumors were then evaluated for tracer distribution using digital autoradiography and compared with histologic markers of tumor hypoxia (pimonidazole, carbonic anydrase 9 [CA9]) and vascular perfusion (Hoechst 33342). Results: The highest tumor uptake was observed with 64Cu-ATSM (maximum standardized uptake values [SUVmax], 1.26 ± 0.13) and the lowest with 18F-FAZA (SUVmax, 0.41 ± 0.24). 18F-FMISO and 18F-HX4 had similar intermediate tumor uptake (SUVmax, 0.76 ± 0.38 and 0.65 ± 0.19, respectively). Digital autoradiographs of hypoxia tracer distributionwere compared pixel by pixelwith images of immunohistochemistry stains. The fluorinated nitroimidazoles all showed radiotracer uptake increasing with pimonidazole and CA9 staining. 64Cu-ATSM showed the opposite pattern, with highest radiotracer uptake observed in regions with the lowest pimonidazole andCA9staining. Conclusion: The fluorinatednitroimidazoles showed similar tumordistributionswhencomparedwithimmunohistochemistry markers of hypoxia. Variations in tumor standardized uptake value and normal tissue distribution may determine the most appropriate clinical setting for each tracer. 64Cu-ATSM showed the highest tumor accumulation and little renal clearance. However, the lack of correlation between 64Cu-ATSM distribution and immunohistochemistry hypoxia markers casts some doubt on the hypoxia selectivity of 64Cu-ATSM.
KW - Animal imaging
KW - Autoradiography
KW - Hypoxia
KW - Immunofluorescence
KW - PET
UR - http://www.scopus.com/inward/record.url?scp=84899489980&partnerID=8YFLogxK
U2 - 10.2967/jnumed.113.126615
DO - 10.2967/jnumed.113.126615
M3 - Article
C2 - 24491409
AN - SCOPUS:84899489980
SN - 0161-5505
VL - 55
SP - 515
EP - 521
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 3
ER -