(188)Re-HDD/lipiodol therapy for hepatocellular carcinoma: an activity escalation study

Eur J Nucl Med Mol Imaging. 2006 Mar;33(3):344-52. doi: 10.1007/s00259-005-1954-1. Epub 2005 Dec 7.

Abstract

Purpose: The aim of this study was to investigate the feasibility of administering increasing activities of (188)Re-4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol ((188)Re-HDD/lipiodol) for the treatment of hepatocellular carcinoma (HCC) in patients with well-compensated cirrhosis.

Methods: The activity levels were increased by 1.1 GBq/step after a 6-week interval without unacceptable adverse events in at least five consecutive patients. Absorbed doses to the various organs were calculated according to the MIRD formalism, based on three gamma-scintigraphic studies. Response was assessed by means of MRI and alpha-fetoprotein (AFP) monitoring.

Results: Thirty-five treatments were carried out in 28 patients. Activities from 4.8 to 7.0 GBq (188)Re-HDD/lipiodol were administered via a transfemoral catheter. The mean absorbed dose to the liver (including tumour) was 7.6+/-2.2, 9.8+/-4.9 and 15.2+/-4.9 Gy for the 4.8-, 5.9- and 7.0-GBq groups, respectively. Treatment was well tolerated at all activity levels. Further escalation of the administered activity was not feasible owing to limitations related to the radiolabelling procedure. Response assessment on MRI showed partial response, stable disease and disease progression in 1, 28 and 2 assessable treatments, respectively. In 8 of 17 treatment sessions with an initially elevated AFP, a reduction ranging from 19% to 97% was observed 6 weeks later.

Conclusion: Following the intra-arterial administration of 4.8-7.0 GBq (188)Re-HDD/lipiodol in patients with HCC and well-compensated liver cirrhosis, no severe adverse events occurred. Further escalation was not feasible owing to limitations in the radiolabelling procedure.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / radiotherapy*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Administration Schedule
  • Feasibility Studies
  • Half-Life
  • Humans
  • Iodized Oil / pharmacokinetics*
  • Iodized Oil / therapeutic use*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / radiotherapy*
  • Metabolic Clearance Rate
  • Middle Aged
  • Organ Specificity
  • Organometallic Compounds / pharmacokinetics*
  • Organometallic Compounds / therapeutic use*
  • Radiation Dosage
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Tissue Distribution
  • Treatment Outcome
  • Whole-Body Counting

Substances

  • 188Re-4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol lipiodol conjugate
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Iodized Oil