Author

Amy Rabideau

Document Type

Honors Capstone Project

Date of Submission

Spring 5-1-2010

Capstone Advisor

Dr. Robert Doyle

Honors Reader

Dr. Jon Zubieta

Capstone Major

Biology

Capstone College

Arts and Science

Audio/Visual Component

no

Capstone Prize Winner

yes

Won Capstone Funding

yes

Honors Categories

Sciences and Engineering

Subject Categories

Biology | Chemistry

Abstract

Vitamin B12 (B12)-based bioprobes were produced and investigated in vitro for studying the B12 uptake pathway in certain cancer cell lines and their target-specific capabilities as imaging and/or contrast agents in vivo. An intrinsic factor (IF)-bound B12 conjugate (B12-ReBQBA) was produced containing rhenium(I) for in vitro analysis of the cubilin-expressing placental choriocarcinoma cell line. B12-ReBQBA has millimolar toxicity in vitro and excitation and emission wavelengths in the visible region, 488 nm and 560 nm, respectively. The rhenium metal in this bioprobe can be readily exchanged for the metastable radioactive metal technetium-99m for in vivo single-positron emission computed tomography (SPECT) scanning. A second B12-based derivative was produced, incorporating a lanthanide metal in a bifunctional macrocycle, 1,4,7,10-tetraazacyclododecane-N,N¢,N¢¢,N¢¢¢-tetraacetic acid (DOTA). Europium(III) and terbium(III) were chelated by B12-enDOTA to produce target-specific imaging agents with unique fluorescent properties. These bioprobes, which excite in the UV region, are currently being tested on breast and pancreatic cancer cell lines, T-47D and MIA PaCa-2, respectively. Future work includes sensitizing the Eu(III) and Tb(III) bioprobes so they excite and emit light in the visible region.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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