New in vivo imaging reagents with increased sensitivity and penetration depth are needed to advance our understanding
of metastases and accelerate the development of therapeutics. The folate receptor (FR) is a promising imaging target that
is up-regulated in many human carcinomas, including cancers of the ovary, breast, pancreas, endometrium, lungs,
kidneys, colon, brain, and myeloid cells. Zymera has developed a self-illuminating Bioluminescence Resonance Energy
Transfer Quantum Dot (BRET-Qdot) nanoprobe conjugated with folate (BQ-Folate) for in vivo imaging of cancers overexpressing
FR. BQ-Folate is a novel nanoprobe formed by co-conjugating Renilla reniformis luciferase enzyme and
folate to near-infrared (NIR) emitting quantum dots. The luciferase substrate, coelenterazine, activates the BQ-Folate
nanoprobe generating luminescence emission in the near-infrared (NIR) region (655 nm) for increased sensitivity and
penetration depth. Because BQ-Folate requires no external light source for light emission, it has significant advantages
for challenging in vivo preclinical optical imaging applications, such as the detection of early stage metastases. Zymera
and OncoMed Pharmaceuticals have demonstrated that in vivo imaging with the BQ-Folate nanoprobe detected the
primary tumor and early stage metastases in an orthotopic NOD/SCID mouse model of human pancreatic cancer.
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