Abstract
Rationale: αvβ3 integrins play an important role in angiogenesis and cell migration of cancers. They are highly expressed on activated endothelial cells of newly formed blood vessels. Here, we compare the targeting characteristics of four 68Ga-labeled multimeric cyclic arginine-glycine-aspartate (RGD)-based tracers in an αvβ3 integrin-expressing tumor model and in a tumor model where 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 were intravenously administered to the mice (0.5 nmol per mouse, 10-20 MBq), followed by microPET/CT imaging and ex vivo biodistribution studies one hour post injection. Nonspecific uptake of the tracers in both models was determined by co-injecting 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 tumor models. Tumor uptake of [68Ga]Ga-FSC-(RGD)3 was significantly higher than that of [68Ga]Ga-DOTA-(RGD)2, [68Ga]Ga-TRAP-(RGD)3, and [68Ga]Ga-THP-(RGD)3, in the SK-RC-52 model, but not in the FaDu model, where [68Ga]Ga-FSC-(RGD)3 showed significantly higher tumor uptake than [68Ga]Ga-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]Ga-FSC-(RGD)3 and [68Ga]Ga-THP-(RGD)3 in the SK-RC-52 and FaDu model, respectively, selection of the most optimal tracer for specific diagnostic applications also depends on tumor-to-blood ratio and uptake in normal tissues, and should therefore also be considered.
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 were intravenously administered to the mice (0.5 nmol per mouse, 10-20 MBq), followed by microPET/CT imaging and ex vivo biodistribution studies one hour post injection. Nonspecific uptake of the tracers in both models was determined by co-injecting 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 tumor models. Tumor uptake of [68Ga]Ga-FSC-(RGD)3 was significantly higher than that of [68Ga]Ga-DOTA-(RGD)2, [68Ga]Ga-TRAP-(RGD)3, and [68Ga]Ga-THP-(RGD)3, in the SK-RC-52 model, but not in the FaDu model, where [68Ga]Ga-FSC-(RGD)3 showed significantly higher tumor uptake than [68Ga]Ga-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]Ga-FSC-(RGD)3 and [68Ga]Ga-THP-(RGD)3 in the SK-RC-52 and FaDu model, respectively, selection of the most optimal tracer for specific diagnostic applications also depends on tumor-to-blood ratio and uptake in normal tissues, and should therefore also be considered.
| Original language | English |
|---|---|
| Pages (from-to) | 1296-1301 |
| Number of pages | 6 |
| Journal | Journal of Nuclear Medicine |
| Volume | 59 |
| Issue number | 8 |
| Early online date | 6 Apr 2018 |
| DOIs | |
| Publication status | Published - 1 Aug 2018 |
Keywords
- 68Ga
- Angiogenesis
- Multimers
- RGD peptides
- αvβ3 integrin
