title: 188Re-HDD/lipiodol therapy for hepatocellular carcinoma: a phase I clinical trial.
abstract: The aim of this study was to investigate the pharmacokinetics, organ dosimetry, and toxicity after the intraarterial administration of (188)Re-labeled 4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol ((188)Re-HDD/lipiodol) for palliative treatment of hepatocellular carcinoma (HCC). A secondary objective was to document the response.
  
  
  METHODS
  A mean activity of 3.60 GBq (188)Re-HDD/lipiodol (range, 1.86-4.14 GBq) was administered to 11 patients (16 treatment sessions) via a transfemoral catheter. The pharmacokinetic and dosimetric data were collected by means of venous blood samples, urine collections, and 4 or 5 gamma-scintigraphies over 76 h. Absorbed doses to the various organs were calculated according to the MIRD formalism, using the MIRDOSE3.1 software. The toxicity was assessed until 6 wk after administration by means of the Common Toxicity Criteria scale. The response was evaluated on MRI and by monitoring of the tumor marker.
  
  
  RESULTS
  A fast blood clearance of the injected activity was observed with a calculated effective half-life of 7.6 +/- 2.2 h (+/-SD) in blood. The predominant elimination of the activity was through urinary excretion with a mean renal clearance of 44.1% +/- 11.7% (+/-SD) of the injected activity within the 76 h after administration. Fecal elimination was negligible. The calculated whole-body effective half-life was 14.3 +/- 0.9 h (+/-SD). The absorbed dose to the liver tissue, the lungs, the kidneys, and the thyroid was 4.5 +/- 1.9, 4.1 +/- 1.2, 0.9 +/- 0.7, and 0.3 +/- 0.1 Gy, respectively. Treatment was well tolerated, except in 2 patients. One Child B patient experienced a worsening of his liver dysfunction (hyperbilirubinemia) and another patient experienced dyspnea and coughing. Response assessment on MRI showed 1 case of partial response, disease stabilization in 11 treatments, and progressive disease in 1 treatment. In 5 of 8 treatment sessions with an initially elevated alpha-fetoprotein, a reduction (range, 19%-90%) was observed 6 wk later.
  
  
  CONCLUSIONS
  After the intraarterial administration of 3.60 GBq (188)Re-HDD/lipiodol, a fast clearance of the activity appearing in the blood is observed and the predominant elimination is through urinary excretion. The tolerance as well as the preliminary response rates of the present phase I study are encouraging.
authors.affiliation: Nuclear Medicine Division, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Bieke.Lambert@Ugent.be
authors.forename: Bieke
authors.initials: B
authors.lastname: Lambert
authors.forename: Klaus
authors.initials: K
authors.lastname: Bacher
authors.forename: Luc
authors.initials: L
authors.lastname: Defreyne
authors.forename: Filip
authors.initials: F
authors.lastname: Gemmel
authors.forename: Hans
authors.initials: H
authors.lastname: Van Vlierberghe
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Christophe
authors.initials: C
authors.lastname: Van de Wiele
authors.forename: Hubert
authors.initials: H
authors.lastname: Thierens
authors.forename: Filip
authors.initials: F
authors.lastname: De Vos
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007459:Iodized Oil / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: C498051:188Re-4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol lipiodol conjugate; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D007459:Iodized Oil