By incubating increasing concentrations of 99mTc-DMTHF with KB human cancer cells, the affinity of 99mTc-DMTHF for FR-α was determined to be comparable to EC20.[1]
This dye conjugate, DMTHF-DyLight 680, showed affinity for FR-α on KB cells, confirming the researchers' previous results.
Specificity
On mice with KB (FR-α-positive) and A549 (FR-α-negative) implanted shoulder tumors, 99mTc-DMTHF was taken up by the KB tumor but not the A549 tumor, demonstrated by radioisotope imaging and biodistribution analysis.[1]
In an
cardiotoxin, the same result with a lack of uptake of 99mTc-DMTHF was observed as expected.[1] Lastly, animals that had ulcerative colitis as well as M109 neck tumors were tested. The tumor displayed similar uptake of 99mTc-EC20 and 99mTc-DMTHF, while only 99mTc-EC20 was observed in the inflamed colon.[1]
This result was supported by DMTHF-dye conjugates. Therefore, DMTHF can be used in vivo to distinguish cancer from sites of inflammation.
Targeting
Imaging
Currently, reliable imaging methods do not exist for isolating cancerous tissue from other diseased tissue, particularly in distinguishing cancer from inflammation.
fluorodeoxyglucose
(FDG) and similar radiolabelled biomolecules can be used to target cancer but also accumulate at sites of infection and inflammation. All of the folate receptor-targeted imaging agents reported in the literature prior to DMTHF could not distinguish between inflammation and cancer. To isolate cancer from inflammation, Low et al. (2012) developed DMTHF-Tc that shows specificity for FR-α. By chelating DMTHF to 99mTc, the same properties that make EC20 a good imaging agent for the FR allow 99mTc-DMTHF to target FR-α reliably.
Therapy
Although no studies to date have explored using a DMTHF-drug conjugate for targeted therapy of cancer, it could be a valuable tool for targeting FR-α expressing malignant tissues.[citation needed] Like an imaging agent, a therapeutic molecule consists of the targeting ligand, DMTHF, with a linker system. Instead of an imaging agent, the molecule would then include a drug payload, such as a chemotherapeutic.
