CLINICAL SIGNS, DIAGNOSIS, AND TREATMENT OF LEAD INTOXICATION IN AN ELECTRIC EEL ( ELECTROPHORUS ELECTRICUS).

An adult, wild-caught electric eel ( Electrophorus electricus), weighing 18 kg and measuring 2 m in length, presented with bilateral swellings behind the pectoral fins, lethargy, and anorexia for 2 days. Anesthesia was performed with immersion in tricaine methanesulphonate and supplemented with 0.11 mg/kg medetomidine and 2.2 mg/kg ketamine intramuscularly. Endoscopy revealed blood in the oral and gastric cavity. The stomach was grossly enlarged, flaccid, and contained a lead wire which was removed manually. Blood lead values were severely elevated. The fish was treated with 28 mg/kg calcium disodium ethylenediaminetetraacetate intramuscularly every 72 hr for 5 doses, which resulted in an improved clinical condition. Because lead values had not decreased to normal values within 4 wk of initial presentation, 35 mg/kg dimercaptosuccinic acid was given orally twice weekly for 3 wk. The electric eel made a full recovery.

DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals.

Earlier studies have shown that modification of the octapeptide octreotide in positions 3 and 8 may result in compounds with increased somatostatin receptor affinity that, if radiolabelled, display improved uptake in somatostatin receptor-positive tumours. The aim of a recent research study in our laboratory was to employ the parallel peptide synthesis approach by further exchanging the amino acid in position 3 of octreotide and coupling the macrocyclic chelator DOTA(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to these peptides for labelling with radiometals like gallium-67 or -68, indium-111, yttrium-90 and lutetium-177. The purpose was to find radiopeptides with an improved somatostatin receptor binding profile in order to extend the spectrum of targeted tumours. A first peptide, [111In,90Y-DOTA]-1-Nal3-octreotide (111In,90Y-DOTA-NOC), was isolated which showed an improved profile. InIII-DOTA-NOC exhibited the following IC50 values (nM) when studied in competition with [125I][Leu8, d-Trp22, Tyr25]somatostatin-28 (values for YIII-DOTA-NOC are shown in parentheses): sstr2, 2.9 +/- 0.1 (3.3 +/- 0.2); sstr3, 8 +/- 2 (26 +/- 1.9); sstr5, 11.2 +/- 3.5 (10.4 +/- 1.6). Affinity towards sstr1 and 4 was very low or absent. InIII-DOTA-NOC is superior to all somatostatin-based radiopeptides having this particular type of binding profile, including DOTA-lanreotide, and has three to four times higher binding affinity to sstr2 than InIII,YIII-DOTA-Tyr3-octreotide (InIII,YIII-DOTA-TOC). In addition, [111In]DOTA-NOC showed a specific and high rate of internalization into AR4-2J rat pancreatic tumour cells which, after 4 h, was about two times higher than that of [111In]DOTA-TOC and three times higher than that of [111In]DOTA-octreotide ([111In]DOTA-OC). The internalized radiopeptides were externalized intact upon 2 h of internalization followed by an acid wash. After 2-3 h of externalization a plateau is reached, indicating a steady-state situation explained by reactivation of the receptors followed by re-endocytosis. Biodistribution studies in CA 20948 tumour-bearing rats showed rapid clearance from all sstr-negative tissues except the kidneys. At 4 h the uptake of [111In]DOTA-NOC in the tumour and sstr-positive tissues, such as adrenals, stomach and pancreas, was three to four times higher than that of [111In]DOTA-TOC. Differential blocking studies indicate that this is at least partially due to the uptake mediated by sstr3 and sstr5. These very promising preclinical data justify the use of this new radiopeptide for imaging and potentially internal radiotherapy studies in patients.