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Indium-111-DTPA-folate as a potential folate-receptor-targeted radiopharmaceutical
C J Mathias1, S Wang, D J Waters
1Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907-1333, USA.
Unlabelled:
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.
Conclusion:
Indium-111-DTPA-folate appears suitable as a radiopharmaceutical for targeting tumor-associated folate receptors.
Insights
Indium-111-DTPA-folate effectively targets tumor folate receptors, showing high tumor uptake in mice. This radiopharmaceutical demonstrates potential for cancer imaging and therapy.
Area of Science:
- Nuclear Medicine
- Radiopharmaceutical Chemistry
- Oncology
Background:
- Tumor-associated folate receptors are overexpressed in various cancers.
- Radiopharmaceuticals targeting these receptors offer potential for diagnostic and therapeutic applications.
Purpose of the Study:
- To evaluate Indium-111-labeled diethylenetriamine pentaacetic acid (DTPA)-folate as a radiopharmaceutical for targeting tumor-associated folate receptors.
Main Methods:
- Athymic mice bearing human nasopharyngeal carcinoma xenografts were injected with Indium-111-DTPA-folate, Indium-111-DTPA, or Indium-111-citrate.
- Tumor uptake and biodistribution were assessed.
- Blocking studies with free folic acid were performed to confirm receptor-mediated uptake.
Main Results:
- Indium-111-DTPA-folate demonstrated marked tumor-specific deposition of Indium-111 in vivo.
- Folate receptor-mediated uptake was confirmed by blocking studies.
- Indium-111-DTPA-folate showed kidney uptake, suggesting binding to renal folate receptors.
- Indium-111-citrate showed tumor uptake but with lower tumor-to-background contrast.
- Unconjugated Indium-111-DTPA exhibited no tumor affinity.
Conclusions:
- Indium-111-DTPA-folate is a promising radiopharmaceutical for targeting tumor-associated folate receptors.
- The conjugate exhibits favorable tumor-targeting characteristics.
- Further investigation is warranted for its clinical application in cancer imaging and therapy.