title: Prodrug enzymes and their applications in image-guided therapy of cancer: tracking prodrug enzymes to minimize collateral damage.
abstract: Many cytotoxic therapies are available to kill cancer cells. Unfortunately, these also inflict significant damage on normal cells. Identifying highly effective cancer treatments that have minimal or no side effects continues to be a major challenge. One of the strategies to minimize damage to normal tissue is to deliver an activating enzyme that localizes only in the tumor and converts a nontoxic prodrug to a cytotoxic agent locally in the tumor. Such strategies have been previously tested but with limited success due in large part to the uncertainty in the delivery and distribution of the enzyme. Imaging the delivery of the enzyme to optimize timing of the prodrug administration to achieve image-guided prodrug therapy would be of immense benefit for this strategy. Here, we have reviewed advances in the incorporation of image guidance in the applications of prodrug enzymes in cancer treatment. These advances demonstrate the feasibility of using clinically translatable imaging in these prodrug enzyme strategies.
authors: JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Marie-France
authors: MF
authors: Penet
authors: Zhihang
authors: Z
authors: Chen
authors: Cong
authors: C
authors: Li
authors: Paul T
authors: PT
authors: Winnard
authors: Zaver M
authors: ZM
authors: Bhujwalla
keywords: Cancer; Imaging; Prodrug enzymes
references: Gastroenterology. 2005 Jun;128(7):1787-95
references: 15940613
references: Bioorg Med Chem. 2009 Jul 15;17(14):4888-93
references: 19541487
references: Mol Ther. 2004 Nov;10(5):916-28
references: 15509509
references: Physiol Rev. 2011 Jul;91(3):1071-121
references: 21742796
references: Cancer Res. 1998 Sep 15;58(18):4075-8
references: 9751613
references: ACS Nano. 2010 Nov 23;4(11):6707-16
references: 20958072
references: J Nucl Med. 2010 Sep;51(9):1395-403
references: 20810757
references: Cancer Lett. 2011 Aug 1;307(1):53-61
references: 21546157
references: Q J Nucl Med. 1999 Jun;43(2):163-9
references: 10429512
references: Curr Pharm Des. 2011;17(32):3527-47
references: 22074425
references: J Nucl Med. 2006 Jul;47(7):1136-43
references: 16818948
references: Adv Drug Deliv Rev. 2011 Jul 18;63(8):659-70
references: 21333700
references: Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):814-25
references: 15701872
references: Hum Gene Ther. 1997 May 20;8(8):985-1001
references: 9195221
references: Magn Reson Med. 2009 Nov;62(5):1300-4
references: 19780183
references: Mol Ther. 2009 Jul;17(7):1292-9
references: 19367257
references: Mol Imaging Biol. 2007 May-Jun;9(3):110-6
references: 17294333
references: NMR Biomed. 2011 May;24(4):343-50
references: 20891022
references: Nat Rev Cancer. 2007 Nov;7(11):870-9
references: 17943135
references: Acta Oncol. 2008;47(7):1211-20
references: 18661431
references: Clin Cancer Res. 2008 Jan 15;14(2):515-22
references: 18223227
references: Cancer Gene Ther. 2011 Nov;18(11):817-24
references: 21869821
references: Int J Cancer. 2000 Feb 15;85(4):571-7
references: 10699932
references: Clin Cancer Res. 2012 Jan 1;18(1):238-47
references: 22019516
references: Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16206-11
references: 21930952
references: Cancer Res. 2007 Feb 15;67(4):1706-15
references: 17308112
references: J Nucl Med. 2010 Jul;51(7):1092-8
references: 20554721
references: Clin Cancer Res. 2001 Nov;7(11):3314-24
references: 11705842
references: J Clin Oncol. 1999 Jul;17(7):2180-9
references: 10561274
references: Gene Ther. 2012 Mar;19(3):295-302
references: 21753794
references: Structure. 1997 Mar 15;5(3):337-47
references: 9083113
references: PLoS One. 2011;6(10):e26142
references: 22028820
references: J Nucl Med. 2008 Apr;49(4):637-48
references: 18344433
references: Nat Rev Cancer. 2003 May;3(5):330-8
references: 12724731
references: Cancer Gene Ther. 2005 Mar;12(3):329-39
references: 15592447
references: Mol Cancer Ther. 2007 Nov;6(11):2928-37
references: 18025277