RT Journal Article
SR Electronic
T1 A Comparison of the Imaging Characteristics and Microregional Distribution of 4 Hypoxia PET Tracers
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 515
OP 521
DO 10.2967/jnumed.113.126615
VO 55
IS 3
A1 Sean Carlin
A1 Hanwen Zhang
A1 Megan Reese
A1 Nicholas N. Ramos
A1 Qing Chen
A1 Sally-Ann Ricketts
YR 2014
UL http://jnm.snmjournals.org/content/55/3/515.abstract
AB We compared the imaging characteristics and hypoxia selectivity of 4 hypoxia PET radiotracers (18F-fluoromisonidazole [18F-FMISO], 18F-flortanidazole [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 distribution were compared pixel by pixel with 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 and CA9 staining. Conclusion: The fluorinated nitroimidazoles showed similar tumor distributions when compared with immunohistochemistry 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.