Use of a novel Arg-Gly-Asp radioligand, 18F-AH111585, to determine changes in tumor vascularity after antitumor therapy.
Despite the recent development of various radiolabeled Arg-Gly-Asp (RGD) peptides for imaging the alphavbeta3 integrin receptor, relatively little attention has been focused on the ability of these radiotracers to monitor changes in tumor vascularity after antitumor therapies. This study describes the favorable in vivo kinetics and tumor-targeting properties of 18F-AH111585, a novel 18F-RGD peptide, and its ability to monitor tumor vascularity noninvasively.


METHODS
Mice bearing Lewis lung carcinoma (LLC) tumors or Calu-6 non-small cell lung tumor xenografts were used for in vivo biodistribution and small-animal PET imaging studies. In addition, some animals were treated with either low-dose paclitaxel or the vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor ZD4190. Tumor uptake of 18F-AH111585 and microvessel density were then assessed.


RESULTS
Biodistribution of 18F-AH111585 demonstrated rapid clearance from the blood and key background organs and good tumor accumulation, with 1.5 percentage injected dose per gram (%ID/g) present at 2 h after injection in LLC tumors. Small-animal PET imaging of Calu-6 tumors allowed visualization of tumors above background tissue, with mean baseline uptake of 2.2 %ID/g. Paclitaxel therapy reduced the microvessel density in LLC tumor-bearing mice and resulted in significantly reduced 18F-AH111585 tumor uptake (P<0.05). ZD4190 therapy resulted in a significant (31.8%) decrease in 18F-AH111585 uptake in Calu-6 tumors, compared with the vehicle control-treated Calu-6 tumors, which had a 26.9% increase in 18F-AH111585 uptake over the same period (P<0.01).


CONCLUSIONS
18F-AH111585 is a promising 18F-labeled RGD tracer that offers a new approach to noninvasively image tumor vasculature. This tracer may reveal important information in the assessment of the impact of antitumor therapies, in particular those that predominantly target tumor blood vessels.
Morrison
Matthew S
MS
GE Healthcare MDx Research, The Grove Centre, Amersham, United Kingdom. matthew.morrison@ge.com
Ricketts
Sally-Ann
SA
Barnett
Jon
J
Cuthbertson
Alan
A
Tessier
Jean
J
Wedge
Stephen R
SR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051379:Mice; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D009842:Oligopeptides / Q000493:pharmacokinetics; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D010455:Peptides / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use
C530281:AH 111585; D000970:Antineoplastic Agents; D009842:Oligopeptides; D010455:Peptides; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014230:Triazoles; C405268:ZD 4190; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D017239:Paclitaxel