Indium-111-DTPA-folate as a potential folate-receptor-targeted radiopharmaceutical

Indium-111-labeled diethylenetriamine pentaacetic acid (DTPA)-folate was evaluated as a radiopharmaceutical for targeting tumor-associated folate receptors. Methods: Athymic mice were subcutaneously inoculated with ~1.8 x 10⁶ folate receptor-positive KB (human nasopharyngeal carcinoma) cells, yielding 0.2- to 0.6-g tumors in 15 days, at which time ¹¹¹In-DTPA- folate, ¹¹¹In-DTPA or ¹¹¹In-citrate was administered by intravenous injection. Results: The ¹¹¹In-DTPA-folate conjugate afforded marked tumor- specific ¹¹¹In deposition in vive using this mouse model. The involvement of the folate receptor in mediating tumor uptake of ¹¹¹In-DTPA-folate was demonstrated by the blocking of tumor uptake by coadministration of free relic acid (intravenous). The ¹¹¹In-DTPA-folate also shows folate receptor-mediated uptake and retention in the kidneys, presumably reflecting radiotracer binding to folate receptors of the proximal tubules. In control experiments, the ¹¹¹In-citrate radiopharmaceutical precursor was also shown to afford significant tumor uptake of ¹¹¹In, but with much poorer tumor-to-background tissue contrast than that obtained with ¹¹¹In-DTPA- folate. Unconjugated ¹¹¹In-DTPA showed no tumor affinity. Conclusion: Indium-111-DTPA-folate appears suitable as a radiopharmaceutical for targeting tumor-associated folate receptors.