Synthesis, relaxation properties and in vivo assessment of a carborane-GdDOTA-monoamide conjugate as an MRI blood pool contrast agent

Org Biomol Chem. 2015 Sep 7;13(33):8912-8. doi: 10.1039/c5ob00876j. Epub 2015 Jul 24.

Abstract

The synthesis, relaxivity measurements and in vivo assessment of a carborane-GdDOTA-monoamide (CB-GdDOTA-MA) amphiphilic conjugate as a blood pool contrast agent (BPCA) is reported. This BPCA exhibited excellent binding (87.4%) with human serum albumin (HSA) and showed a higher relaxivity value (r1 = 6.8 mM(-1) s(-1), 7 T) as compared to the clinically used BPCA, MS-325 (r1 = 5.1 mM(-1) s(-1), 9.4 T) in PBS. The blood pool contrast enhancement (CE) capability of CB-GdDOTA-MA was evaluated by performing MR angiography (MRA) in CF1 mice (n = 4) at a Gd dose of 0.1 mmol per kg body weight. The significant CE of blood vessels persisted for about 3-4 min post-injection (p.i.) and quickly diminishes over time. The significant CE of the bladder for up to 3 h p.i. indicated that the renal system is the primary clearance pathway for CB-GdDOTA-MA. However, the CE of liver tissues and intestine (up to 24 h p.i.) is suggestive of a significant hepatic uptake of the CB-GdDOTA-MA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Boranes / chemical synthesis*
  • Boranes / chemistry
  • Contrast Media / chemical synthesis*
  • Contrast Media / chemistry
  • Gated Blood-Pool Imaging*
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Humans
  • Magnetic Resonance Angiography
  • Magnetic Resonance Imaging*
  • Mice
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Serum Albumin / metabolism
  • Spectrophotometry, Atomic

Substances

  • Boranes
  • Contrast Media
  • Heterocyclic Compounds
  • Organometallic Compounds
  • Serum Albumin
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate