RT Journal Article
SR Electronic
T1 In Vivo Characterization of 4 <sup>68</sup>Ga-Labeled Multimeric RGD Peptides to Image α<sub>v</sub>β<sub>3</sub> Integrin Expression in 2 Human Tumor Xenograft Mouse Models
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1296
OP 1301
DO 10.2967/jnumed.117.206979
VO 59
IS 8
A1 Daphne Lobeek
A1 Gerben M. Franssen
A1 Michelle T. Ma
A1 Hans-Jürgen Wester
A1 Clemens Decristoforo
A1 Wim J.G. Oyen
A1 Otto C. Boerman
A1 Samantha Y.A. Terry
A1 Mark Rijpkema
YR 2018
UL http://jnm.snmjournals.org/content/59/8/1296.abstract
AB αvβ3 integrins play an important role in angiogenesis and cell migration in cancer and are highly expressed on the activated endothelial cells of newly formed blood vessels. Here, we compare the targeting characteristics of 4 68Ga-labeled multimeric cyclic arginine-glycine-aspartate (RGD)–based tracers in an αvβ3 integrin–expressing tumor model and a tumor model in which αvβ3 integrin is expressed solely on the neovasculature. Methods: Female BALB/c nude mice were subcutaneously injected with SK-RC-52 (αvβ3 integrin–positive) or FaDu (αvβ3 integrin–negative) tumor cells. 68Ga-labeled DOTA-(RGD)2, TRAP-(RGD)3, FSC-(RGD)3, or THP-(RGD)3 was intravenously administered to the mice (0.5 nmol per mouse, 10–20 MBq), followed by small-animal PET/CT imaging and ex vivo biodistribution studies 1 h after injection. Nonspecific uptake of the tracers in both models was determined by coinjecting an excess of unlabeled DOTA-(RGD)2 (50 nmol) along with the radiolabeled tracers. Results: Imaging and biodistribution data showed specific uptake in the tumors for each tracer in both models. Tumor uptake of 68Ga-FSC-(RGD)3 was significantly higher than that of 68Ga-DOTA-(RGD)2, 68Ga-TRAP-(RGD)3, or 68Ga-THP-(RGD)3 in the SK-RC-52 model but not in the FaDu model, in which 68Ga-FSC-(RGD)3 showed significantly higher tumor uptake than 68Ga-TRAP-(RGD)3. Most importantly, differences were also observed in normal tissues and in tumor-to-blood ratios. Conclusion: All tracers showed sufficient targeting of αvβ3 integrin expression to allow for tumor detection. Although the highest tumor uptake was found for 68Ga-FSC-(RGD)3 and 68Ga-THP-(RGD)3 in the SK-RC-52 and FaDu models, respectively, selection of the optimal tracer for specific diagnostic applications also depends on tumor-to-blood ratio and uptake in normal tissues; these factors should therefore also be considered.