A potential role for imaging technology in anticancer efficacy evaluations.
The introduction of imaging methods suitable for rodents offers opportunities for new anticancer efficacy models. Traditional models do not provide the level of sensitivity afforded by these precise and quantitative techniques. Bioluminescent endpoints, now feasible because of sensitive charge-coupled device cameras, can be non-invasively detected in live animals. Currently, the most common luminescence endpoint is firefly luciferase, which, in the presence of O(2) and ATP, catalyses the cleavage of the substrate luciferin and results in the emission of a photon of light. In vivo implantation of tumour cells transfected with the luciferase gene allows sequential monitoring of tumour growth within the viscera by measuring these photon signals. Furthermore, tumour cell lines containing the luciferase gene transcribed from an inducible promoter offer opportunities to study molecular-target modulation without the need for ex vivo evaluations of serial tumour samples. In conjunction with this, transgenic mice bearing a luciferase reporter mechanism can be used to monitor the tumour microenvironment as well as to signal when transforming events occur. This technology has the potential to reshape the efficacy evaluations and drug-testing algorithms of the future.
Hollingshead
M G
MG
Developmental Therapeutics Program, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD 20892, USA. hollingm@mail.nih.gov
Bonomi
C A
CA
Borgel
S D
SD
Carter
J P
JP
Shoemaker
R
R
Melillo
G
G
Sausville
E A
EA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004341:Drug Evaluation; D006801:Humans; D008156:Luciferases; D008163:Luminescent Measurements; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010781:Photography
D000970:Antineoplastic Agents; D008156:Luciferases