Positron emission tomography (PET): Expanding the horizons of oncology drug development

Lisa A. Hammond, Louis Denis, Umber Salman, Paul Jerabek, Charles Thomas, John G. Kuhn

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Positron emission tomography (PET) allows three-dimensional quantitative determination of the distribution of radioactivity permitting measurement of physiological, biochemical, and pharmacological functions at the molecular level. Until recently, no method existed to directly and noninvasively assess transport and metabolism of neoplastic agents as a function of time in various organs as well as in the tumor. Standard preclinical evaluation of potential anticancer agents entails radiolabeling the agent, usually with tritium or 14C, sacrifice experiments, and high-performance liquid chromatography (HPLC) analysis to determine the biodistribution and metabolism in animals. Radiolabeling agents with positron-emitting radionuclides allows the same information to be obtained as well as in vivo pharmacokinetic (PK) data by animal tissue and plasma sampling in combination with PET scanning. In phase I/II human studies, classic PK measurements can be coupled with imaging measurements to define an optimal dosing schedule and help formulate the design of phase III studies that are essential for drug licensure [1]. Many of the novel agents currently in development are cytostatic rather than cytotoxic and therefore, the traditional standard endpoints in phase I and II studies may no longer be relevant. The use of a specialized imaging modality that allows PK and pharmacodynamic (PD) evaluation of a drug of interest has been proposed to permit rapid and sensitive assessment of the biological effects of novel anticancer agents. The progress to date and the challenges of incorporating PET technology into oncology drug development from the preclinical to clinical setting are reviewed in this article.

Original languageEnglish (US)
Pages (from-to)309-340
Number of pages32
JournalInvestigational New Drugs
Volume21
Issue number3
DOIs
StatePublished - Aug 2003
Externally publishedYes

Fingerprint

Positron-Emission Tomography
Pharmacokinetics
Antineoplastic Agents
Pharmaceutical Preparations
Essential Drugs
Drug Evaluation
Tritium
Cytostatic Agents
Licensure
Radioisotopes
Radioactivity
Appointments and Schedules
High Pressure Liquid Chromatography
Pharmacology
Electrons
Technology
Neoplasms

Keywords

  • Oncology drug development
  • Positron emission tomography

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Positron emission tomography (PET) : Expanding the horizons of oncology drug development. / Hammond, Lisa A.; Denis, Louis; Salman, Umber; Jerabek, Paul; Thomas, Charles; Kuhn, John G.

In: Investigational New Drugs, Vol. 21, No. 3, 08.2003, p. 309-340.

Research output: Contribution to journalArticle

Hammond, Lisa A. ; Denis, Louis ; Salman, Umber ; Jerabek, Paul ; Thomas, Charles ; Kuhn, John G. / Positron emission tomography (PET) : Expanding the horizons of oncology drug development. In: Investigational New Drugs. 2003 ; Vol. 21, No. 3. pp. 309-340.
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