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 approximately 1.8 x 10(6) folate receptor-positive KB (human nasopharyngeal carcinoma) cells, yielding 0.2- to 0.6-g tumors in 15 days, at which time (111)In-DTPA-folate, (111)In-DTPA or (111)In-citrate was administered by intravenous injection.


RESULTS
The (111)In-DTPA-folate conjugate afforded marked tumor-specific (111)In deposition in vivo using this mouse model. The involvement of the folate receptor in mediating tumor uptake of (111)In-DTPA-folate was demonstrated by the blocking of tumor uptake by coadministration of free folic acid (intravenous). The (111)In-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 (111)In-citrate radiopharmaceutical precursor was also shown to afford significant tumor uptake of (111)In, but with much poorer tumor-to-background tissue contrast than that obtained with (111)In-DTPA-folate. Unconjugated (111)In-DTPA showed no tumor affinity.


CONCLUSIONS
Indium-111-DTPA-folate appears suitable as a radiopharmaceutical for targeting tumor-associated folate receptors.
Mathias
C J
CJ
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907-1333, USA.
Wang
S
S
Waters
D J
DJ
Turek
J J
JJ
Low
P S
PS
Green
M A
MA
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism; D005240:Feasibility Studies; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007624:KB Cells; D007687:Kidney Tubules, Proximal / Q000000981:diagnostic imaging; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D014018:Tissue Distribution
D002352:Carrier Proteins; C108951:DTPA folate; D058973:Folate Receptors, GPI-Anchored; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D011956:Receptors, Cell Surface; D004369:Pentetic Acid; D005492:Folic Acid