Synthesis of [99mTc]DTPA-folate and its evaluation as a folate-receptor-targeted radiopharmaceutical

Carla J. Mathias, David Hubers, Philip S. Low, Mark A. Green

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

A DTPA-folate conjugate was radiolabeled with 99mTc by stannous chloride reduction of [99mTc]sodium pertechnetate in an aqueous solution of DTPA-folate. The radiochemical purity of the product consistently exceeded 97%, as assessed by thin-layer chromatography employing conditions analogous to those for radiochemical quality control of the radiopharmaceutical [99mTc]DTPA. HPLC demonstrated that the radiolabeled product resulted from the intact DTPA-folate conjugate and not unconjugated DTPA. The ability of [99mTc]DTPA-folate to target folate receptors in vivo was assessed in biodistribution studies with athymic mice bearing subcutaneous folate-receptor-positive human KB cell tumors. As an internal control, previously studied [111In]DTPA-folate was coinjected with the [99mTc]DTPA-folate, along with varying amounts of DTPA-folate (0.38 mg/kg, 1.6 mg/kg, or 14 mg/kg). At each DTPA-folate dose, [99mTc]DTPA-folate exhibited tumor uptake comparable to that of the coadministered [111In]DTPA-folate, with radiotracer levels declining at the higher DTPA-folate doses due to competitive receptor binding of the unlabeled conjugate. Tumor uptake of both tracers was also competitively blocked by preadministered folic acid dihydrate (2.9 mg/kg). Tumor-to-background tissue contrast obtained with [99mTc]DTPA-folate was generally similar to that obtained with [111In]DTPA-folate. The 99mTc-labeled DTPA-folate conjugate may have utility as a targeted radiopharmaceutical for imaging neoplastic tissues known to overexpress the folate receptor.

Original languageEnglish (US)
Pages (from-to)253-257
Number of pages5
JournalBioconjugate Chemistry
Volume11
Issue number2
DOIs
StatePublished - Mar 2000

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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