Abstract
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Objectives FDG is predominantly used for detection of malignant tumors, its use is limited by the off-target uptake in brain, inflammatory sites etc. as well as the cost and availability in larger cities. There is an urgent need for agents which have comparable properties of 18F-FDG and is cost effective. Recent discoveries have shown that genistein based flavonoids binds to multiple targets, such as glucose transporter-GLUT-1 and cell surface receptors. The GLUT-1 transporter is overexpressed in most of the cancers and contributes to constitutive activation of downstream pathways. RadioMedix is developing RMX-SC-11 and RMX-SC-12 agents.
Methods RMX-SC agents were synthesized by conjugating DOTA-NH2 to the terminal -COOH group of scutellarin, either directly (RMX-SC-11) or by separating them by a linker (RMX-SC-12). Their 68Ga-labeling proceeded in 0.5M NaOAc pH=4.1 at 95oC for 10min (68Ge/68Ga generator (ITG GmbH Germany) and purified using C18 sepak cartridges. The cellular uptake of these agents was studied in breast (SKBR-3, MCF-7), prostate (PC-3, LNCaP) and lung (A549) cancer. 68Ga-labeled agent were validated as PET agents in xenograft model of SKBR-3 and PC-3 using Genisys 4 microPET in a static imaging mode at 0min, 30min, 60min and 90min post injection.
Results Both RMX-SC-11 and SC-12 showed higher uptake in different cell lines as compared to DOTA only control. The internalization studies showed a rapid uptake of these molecules suggesting very high affinity to its targets. This was also true in animals models, as RMX-SC-11 and SC-12 showed uptake in tumor in as low as 30min. The time-activity analysis in tumor shows that both agents remained at tumor site for as long as 120 minutes, whereas other organs showed faster clearance. Both agents shows relatively higher liver uptake, which is due to their known metabolism process liver.
Conclusions These studies show that both RMX-SC-11 and SC-12 agent have desirable characteristic for PET diagnostic imaging. Further clinical studies are underway to validate its efficacy in humans.