Synthesis and biological evaluation of water-soluble progesterone-conjugated probes for magnetic resonance imaging of hormone related cancers.

Abstract

Progesterone receptor (PR) is strongly associated with disease prognosis and therapeutic efficacy in hormone-related diseases such as endometriosis and breast, ovarian, and uterine cancers. Receptor status is currently determined by immunohistochemistry assays. However, noninvasive PR imaging agents could improve disease detection and help elucidate pathological molecular pathways, leading to new therapies and animal disease models. A series of water-soluble PR-targeted magnetic resonance imaging (MRI) probes were synthesized using Cu(I)-catalyzed click chemistry and evaluated in vitro and in vivo. These agents demonstrated activation of PR in vitro and preferential accumulation in PR(+) compared to PR(-) human breast cancer cells with low toxicity. In xenograft tumor models, the agents demonstrated enhanced signal intensity in PR(+) tumors compared to PR(-) tumors. The results suggest that these agents may be promising MRI probes for PR(+) diseases.

• Authors: Preeti A Sukerkar, Keith W MacRenaris, Taryn R Townsend, Roshan A Ahmed, Joanna E Burdette, Thomas J Meade
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 22 Issue 11 Pg. 2304-16 (Nov 16 2011) ISSN: 1520-4812 [Electronic] United States
• PMID: 21972997 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Azides
• Contrast Media
• Receptors, Progesterone
• Water
• Europium
• Progesterone
• Gadolinium

Topics

• Animals
• Azides (chemical synthesis, chemistry, metabolism)
• Click Chemistry (methods)
• Contrast Media (chemical synthesis, chemistry, metabolism)
• Europium (chemistry)
• Female
• Gadolinium (chemistry)
• Humans
• Magnetic Resonance Imaging (methods)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Molecular Structure
• Neoplasm Transplantation
• Neoplasms, Experimental (diagnosis, metabolism, pathology)
• Progesterone (chemistry, metabolism)
• Receptors, Progesterone (genetics, metabolism)
• Water (chemistry)