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

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

Research output: Contribution to journalArticle

85 Citations (Scopus)

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
Externally publishedYes

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Radiopharmaceuticals
Folic Acid
Tumors
Bearings (structural)
Tissue
Thin layer chromatography
Quality control
Sodium
Pentetic Acid
Imaging techniques
Acids
DTPA folate
Neoplasms
KB Cells
Sodium Pertechnetate Tc 99m
Competitive Binding
Thin Layer Chromatography
Nude Mice
Quality Control

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Clinical Biochemistry
  • Chemistry(all)
  • Organic Chemistry

Cite this

Synthesis of [99mTc]DTPA-folate and its evaluation as a folate-receptor-targeted radiopharmaceutical. / Mathias, Carla J.; Hubers, David; Low, Philip S.; Green, Mark.

In: Bioconjugate Chemistry, Vol. 11, No. 2, 03.2000, p. 253-257.

Research output: Contribution to journalArticle

Mathias, Carla J. ; Hubers, David ; Low, Philip S. ; Green, Mark. / Synthesis of [99mTc]DTPA-folate and its evaluation as a folate-receptor-targeted radiopharmaceutical. In: Bioconjugate Chemistry. 2000 ; Vol. 11, No. 2. pp. 253-257.
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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.",
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