In vitro and in vivo studies with no-carrier added radioiodinated MIBG

Q J Nucl Med. 1995 Dec;39(4 Suppl 1):72-7.

Abstract

An important drawback of radioiodinated MIBG prepared by isotopic exchange (maximum specific activity: 100 Ci/mmol) is that a considerable amount of carrier is present in the "ready to use" radiopharmaceutical, thus affecting MIBG uptake in the target cells. To improve the therapeutic utility of MIBG an interesting method was developed for the no-carrier-added (n.c.a.) radioiodination of MIBG via a halodesilylation reaction using 3-trimethylsilybenzylguanidine (TMSBG) as precursor. In order to investigate its possible clinical usefulness, n.c.a. [125I]- and [131I]MIBG was prepared according this procedure. HPLC analysis of the labeling mixture showed that the labeling yield reached values greater than 98% within 20 minutes at 70 degrees C. HPLC fraction containing [131I]MIBG was then recovered and tetrahydrofurane was removed under nitrogen stream. Biodistribution studies were performed in BALB/c normal mice and compared with those obtained using [131I]MIBG prepared by isotopic exchange. Preliminary results showed that at 4 hours myocardial uptake was significantly higher than that of c.a. MIBG (20.3 +/- 0.4 %ID/g). Adrenal uptake gradually increased over time; at 24 hours adrenal uptake was almost twofold that a 1 hour. MIBG uptake was also studied in the human neuroblastoma cell line SH-SY5Y which has a specific uptake system for MIBG. The kinetic parameters for MIBG in this line are: km = 0.27 +/- 0.03 microM, Vmax = 39.5 + 1.8 pmol/10(6) cell/10 min. Preliminary data from in vitro binding studies showed that significantly higher levels of specifically incorporated radioactivity can be achieved using n.c.a. [125I]MIBG instead of c.a. [125I]MIBG.

Publication types

  • Comparative Study

MeSH terms

  • 3-Iodobenzylguanidine
  • Adrenal Glands / metabolism
  • Adrenergic Uptake Inhibitors / pharmacology
  • Animals
  • Benzoates / chemistry
  • Chromatography, High Pressure Liquid
  • Furans / chemistry
  • Guanidines / chemistry
  • Humans
  • Imipramine / pharmacology
  • Iodine Radioisotopes / chemistry
  • Iodine Radioisotopes / pharmacokinetics
  • Iodine Radioisotopes / therapeutic use*
  • Iodobenzenes / chemical synthesis
  • Iodobenzenes / chemistry
  • Iodobenzenes / pharmacokinetics
  • Iodobenzenes / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Myocardium / metabolism
  • Neuroblastoma / metabolism
  • Neuroblastoma / radiotherapy*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use*
  • Solvents / chemistry
  • Tissue Distribution
  • Trimethylsilyl Compounds / chemistry
  • Tumor Cells, Cultured

Substances

  • Adrenergic Uptake Inhibitors
  • Benzoates
  • Furans
  • Guanidines
  • Iodine Radioisotopes
  • Iodobenzenes
  • Radiopharmaceuticals
  • Solvents
  • Trimethylsilyl Compounds
  • 3-trimethylsilylbenzylguanidine
  • 3-Iodobenzylguanidine
  • tetrahydrofuran
  • Imipramine