Indium-111 labelled DTPA-D-Phe(1)-octreotide (DTPA-OC, OctreoScan) has been introduced into clinical routine for the detection of somatostatin receptor (SSTR)-positive tumours, which are predominantly of neuroendocrine origin, Potential further applications in other SSTR-positive cancers (e.g, small cell lung cancer, breast cancer, melanoma) have been limited mainly by the restricted availability and the high radionuclide costs. Previous attempts to introduce technetium-99m labelled analogues of octreotide have not been very successful in terms of the labelling procedure, in vive biodistribution and/or tumour detection capabilities. The aim of this study was to assess the performance of the new Tc-99m-labelled analogue HYNIC-D-Phe(1)-Tyr(3)-oct-reotide (HYNIC-TOC), using tricine as co-ligand, for the detection of SSTR-positive tumours in patients in comparison with In-111-DTPA-OC. Overall, 13 patients were examined using Tc-99m-tricine- YNIC-TOC. Twelve patients had proven SSTR-positive turnours, while one patient presented with an SSTR-negative tumour. In 9 of the, 13 patients both tracers (Tc-99m-tricine-HYNIC-TOC and In-111-DTPA-OC) were used. Serial whole-body scans, spot views and/or single-photon emission tomography studies were performed. Images were qualitatively and semi-quantitatively (ROI analyses) evaluated. The biodistribution of Tc-99m-tricine-HYNIC-TOC in patients showed high physiological uptake in kidneys, moderate uptake in liver and spleen and little uptake in the gut. The tracer showed predominantly renal and negligible hepatobiliary excretion. Known SSTR-positive tumour sites showed rapid and intense tracer accumulation, Tc-99m-tricine-HYNIC-TOC demonstrated rapid tissue uptake within the first hour after injection and had basically no significant clearance (<20%) from normal or tumour tissue thereafter: In contrast, In-111-DTPA-OC showed continuous clearance from normal tissues as well as renal and very little hepatobiliary excretion. Nevertheless, the patterns of accumulation of Tc-99m-tricine-HYNIC-TOC in tumours and normal organs were comparable to those of In-111-DTPA-OC, A lesion-by-lesion comparison showed comparable tumour detection capabilities in intrahepatic tumour sites and superior capabilities of Tc-99m-tricine-HYNIC-TOC in respect of extrahepatic lesions. In conclusion, Tc-99m-tricine-HYNIC-TOC shows promise as a tracer for SSTR imaging, given its favourable clinical characteristics (specific and high receptor affinity, food biodistribution, renal excretion, low radiation exposure, high imaging quality, on-demand availability) and cost-effectiveness, Tc-99m-tricine-HYNIC-TOC allows earlier diagnosis (10 min-4h) compared with In-111-DTPA-OC (4-24 h).