Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters.

• The radio-iodinated noradrenaline analogue meta-iodobenzylguanidine (MIBG) can be used for scintigraphy and radiation therapy of neuroendocrine (NE). The aim of the present study was to study the importance of vesicular monoamine transporters (VMATs) for the uptake of (123)I-MIBG in NE tumours. In nude mice, bearing the human transplantable midgut carcinoid GOT1, all organs and xenografted tumours accumulated (123)I after i.v. injection of (123)I-MIBG. A high concentration of (123)I was maintained in GOT1 tumours and adrenals, which expressed VMATs, but rapidly decreased in all other tissues. In the VMAT-expressing NE tumour cell lines GOT1 and BON and in VMAT-expressing primary NE tumour cell cultures (carcinoids, n=4 and pheochromocytomas, n=4), reserpine significantly reduced the uptake of (123)I-MIBG. The membrane pump inhibitor clomipramine had no effect on the uptake of (123)I-MIBG in GOT1 and BON cells, but inhibited the uptake in one out of four primary carcinoid cell cultures and three out of four primary pheochromocytoma cell cultures. In conclusion, VMATs and secretory granules are of importance for the uptake and retention of (123)I-MIBG in NE tumours. Information about the type and degree of expression of VMATs in NE tumours may be helpful in future to select patients suitable for radiation therapy with radio-iodinated MIBG.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

3-Iodobenzylguanidine

pharmacokinetics

Adrenal Gland Neoplasms

metabolism

Adrenergic Uptake Inhibitors

pharmacology

Animals

Antineoplastic Agents

pharmacokinetics

Blotting

Western

Chromogranin A

Chromogranins

metabolism

Clomipramine

pharmacology

Humans

Immunoenzyme Techniques

Iodine Radioisotopes

pharmacokinetics

Male

Membrane Glycoproteins

metabolism

Membrane Transport Proteins

Mice

Mice

Inbred BALB C

Mice

Nude

Nerve Tissue Proteins

metabolism

Neuroendocrine Tumors

metabolism

Neuropeptides

Pheochromocytoma

metabolism

Reserpine

pharmacology

Serotonin Uptake Inhibitors

pharmacology

Tumor Cells

Cultured

metabolism

Vesicular Biogenic Amine Transport Proteins

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