PET for in vivo pharmacokinetic and pharmacodynamic measurements.
Positron emission tomography (PET) scanning is evolving as a unique tool for drug development in oncology for improving both the efficacy of established treatment and in evaluating novel anticancer agents. As a non-invasive functional imaging modality, PET has an unrivalled sensitivity when monitoring the pharmacokinetics and pharmacodynamics of drugs and biochemicals when radiolabelled with short living positron-emitting radioisotopes. This is of particular relevance in assessing newer molecular-targeted therapy where conventional evaluation criteria (maximum tolerated dose and tumour shrinkage for example) may be inappropriate. PET has already been applied to a wide number of drugs to demonstrate activity in vivo from standard chemotherapy such as 5-fluorouracil (5-FU) [J Clin Oncol 17 (1999) 1580], to novel molecular agents such as those involved in tumour angiogenesis [Br J Cancer 83 (2000) P6] and antivascular therapy [Proc Annu Meet Am Soc Clin Oncol 19 (2000) 179a]. This review will evaluate the achievements of PET in the drug development process, an approach that promises to facilitate the rapid translation of scientific research into current clinical practice.
Gupta
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Cancer Research UK PET Oncology Group, Section of Cancer Therapeutics, Imperial College of Science, Technology and Medicine, MRC Cyclotron Unit, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
Price
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PM
Aboagye
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EO
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D002455:Cell Division; D015687:Cell Hypoxia; D017321:Clinical Trials, Phase I as Topic; D018432:Drug Resistance, Multiple; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D011355:Prodrugs; D019275:Radiopharmaceuticals; D011955:Receptors, Drug / Q000032:analysis; D014055:Tomography, Emission-Computed / Q000379:methods*
D000906:Antibodies; D000970:Antineoplastic Agents; D011355:Prodrugs; D019275:Radiopharmaceuticals; D011955:Receptors, Drug