IN-VIVO PROPERTIES OF I-125 SOMATOSTATIN-DEXTRAN CONJUGATES

Somatostatin analogues are frequently used clinically in the diagnosis and treatment of neuroendocrine tumours. Recently, somatostatin was c onjugated to dextran yielding a conjugate with a greater radionuclide carrying capacity. The conjugate can be potentially useful in the trea tment of neuroendocrine tumours. This study investigates the in vivo p roperties of the somatostatin-dextran conjugate. The peptide part of t he conjugate was labelled with I-125 using the Bolton & Hunter method. Female Sprague Dawley rats were injected in the tail vein with approx imately 15 mu g of dextran bound somatostatin labelled with 0.3-0.8 MB q I-125. At different time intervals, urine, faeces, blood, and organs were collected and analysed. The excretion of the conjugate was mainl y through the kidneys. Gel filtration of urine showed that after 12h, 45% of the radioactivity was found in high molecular weight fractions, indicating an intact conjugate. After 24h, this figure decreased to 6 %. In 24h most of the radioactivity was excreted (i.e. not including p ersisting radioactivity in the thyroid). The thyroid had the highest u ptake, 40% dose/g tissue after 24h, probably because of dehalogenation . Among the other organs, kidneys, liver and spleen had the highest up take, 0.25-0.9% dose/g tissue. The half-life in blood was dependent on two compartments, the first approximately 4h, and the second approxim ately 8h, This shows that the half-life of somatostatin can be conside rably prolonged by conjugation to dextran since the half-life of uncon jugated somatostatin is less than three minutes. The somatostatin-dext ran conjugate showed favourable properties that motivate further study .