PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer

J Nucl Med. 2004 Nov;45(11):1966-71.

Abstract

16 beta-fluoro-5 alpha-dihydrotestosterone (FDHT) is a promising new PET radiopharmaceutical for the imaging of prostate cancer. A recent clinical trial provided the opportunity for refinement of normal-tissue radiation-absorbed dose estimates based on quantitative PET. The objective of the current study was to derive estimates of normal-tissue absorbed doses for (18)F-FDHT administered to patients with advanced prostate cancer.

Methods: Absorbed dose estimates were derived from 10 (18)F-FDHT PET studies (administered activity, 111-407 MBq) of 7 prostate cancer patients. Activity concentrations in plasma and red marrow (assuming a plasmacrit of 0.58, an extracellular fluid fraction of 0.40, and equilibration of activity between plasma and marrow extracellular fluid) were measured ex vivo from a peripheral blood sample. Liver, spleen, urinary bladder contents, and total-body activities were measured by region-of-interest analysis of quantitative whole-body studies acquired with a dedicated PET scanner. Total organ activities and residence times were calculated from the respective PET scan-derived activity concentrations assuming standard (70 kg) man organ masses. Urinary excretion was corrected for hepatobiliary excretion (liver activity), and a first-order adjustment was made for the bladder-wall mass based on the patient's total-body mass. Mean organ absorbed doses were calculated with the MIRD formalism and the standard man model using the MIRDOSE3 software program.

Results: The absorbed doses (mean +/- SD) ranged from 0.00057 +/- 0.000281 cGy/MBq (to skin) to 0.00868 +/- 0.00481 cGy/MBq (to bladder wall) (voiding intervals, 1-2 h), and the effective dose equivalent was 0.00177 +/- 0.000152 cSv/MBq.

Conclusion: The maximum absorbed dose among all tissues in all 10 studies, 0.0151 cGy/MBq, occurred for the urinary bladder wall (with hydration and 1- to 2-h voiding intervals). To ensure that the maximum normal-tissue absorbed dose is kept below the recommended maximum permissible dose of 5 cGy per single administration, a maximum administered activity of 331 MBq (5 cGy/[0.0151 cGy/MBq]) is recommended for (18)F-FDHT.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Body Burden
  • Dihydrotestosterone / analogs & derivatives*
  • Dihydrotestosterone / pharmacokinetics*
  • Humans
  • Image Interpretation, Computer-Assisted / methods*
  • Male
  • Metabolic Clearance Rate
  • Organ Specificity
  • Positron-Emission Tomography / methods*
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / metabolism*
  • Radiation Dosage
  • Radiation Protection / methods*
  • Radiometry / methods*
  • Relative Biological Effectiveness
  • Risk Assessment / methods
  • Risk Factors
  • Tissue Distribution
  • Whole-Body Counting / methods*

Substances

  • 16-fluorodihydrotestosterone
  • Dihydrotestosterone