Tumor-Selective Radiopharmaceutical Targeting via Receptor-Mediated Endocytosis of Gallium-67-Deferoxamine-Folate

Carla J. Mathias, Susan Wang, Robert J. Lee, David J. Waters, Philip S. Low, Mark A. Green

Research output: Contribution to journalArticlepeer-review

185 Scopus citations


The receptor-mediated endocytosis uptake pathway for the vitamin folate was investigated as a target for tumor-selective radiopharmaceutical delivery. The molecular target for this delivery mechanism is a membrane-associated folate binding protein (FBP) that is overexpressed by a variety of malignant cell lines. Methods: The ability of a 67Ga-labeled deferoxamine-folate conjugate (67Ga-DF-folate) to target tumor cells in vivo was examined using an athymic mouse tumor model. Subcutaneous inoculation of ∼4 × 106 folate-receptor-positive KB (human nasopharyngeal carcinoma) cells into athymic mice yielded ∼0.20 g tumors in 15 days, at which time either 67Ga-DF-folate, 67Ga-deferoxamine (67Ga-DF) or 67Ga-citrate was administered by intravenous injection. Results: The 67Ga-DF-folate conjugate showed marked tumor-specific deposition in vivo, with 1.0 ± 0.3% of the injected dose (%ID) in tumor at 4 hr postinjection (equating to 5.2 ± 1.5 %ID/g tumor; n = 3 mice). Corresponding tumor-to-background ratios at 4 hr postinjection were: tumor/blood = 409 ± 195; tumor/muscle = 124 ± 47; tumor/liver = 11 ± 3; and tumor/kidney = 2.6 ± 0.9. Tumor uptake of 67Ga-DF-folate conjugate was effectively blocked by co-injection of 2.4 ± 1.0 mg free folate. In control experiments, 67Ga-citrate exhibited tumor uptake of 2.2 ± 0.4% of the injected dose (10.9 ± 0.2 %ID/g tumor), but very poor target-to-background contrast (tumor/blood = 0.84 ± 0.19; tumor/muscle = 5.4 ± 0.7; tumor/liver = 2.3 ± 0.2; and tumor/kidney = 2.4 ± 0.3). Unconjugated 67Ga-deferoxamine showed no tumor affinity. Conclusion: Receptor-mediated endocytosis of radiolabeled folate-conjugates may offer a suitable mechanism for selectively delivering radiopharmaceuticals to tumors for diagnostic imaging and/or radiation therapy.

Original languageEnglish (US)
Pages (from-to)1003-1008
Number of pages6
JournalJournal of Nuclear Medicine
Issue number6
StatePublished - 1996


  • Folate binding protein
  • Gallium-67
  • Receptor-mediated endocytosis
  • Tumor imaging

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology


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