Detection of somatostatin receptor-positive tumours using the new 99m Tc-tricine-HYNIC- d -Phe 1 -Tyr 3 -octreotide: first results in patients and comparison with 111 In-DTPA- d -Phe 1 -octreotide

Abstract

Indium- 111 labelled DTPA-D-Phe1-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 vivo biodistribution and/or tumour detection capabilities. The aim of this study was to assess the performance of the new 99mTc-labelled analogue HYNIC-D-Phe1-Tyr3-octreotide (HYNIC-TOC), using tricine as co-ligand, for the detection of SSTR-positive tumours in patients in comparison with 111In-DTPA-OC. Overall, 13 patients were examined using 99mTc-tricine-HYNIC-TOC. Twelve patients had proven SSTR-positive tumours, while one patient presented with an SSTR-negative tumour. In 9 of the 13 patients both tracers (99mTc-tricine-HYNIC-TOC and 111In-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 99mTc-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. 99mTc-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, 111In-DTPA-OC showed continuous clearance from normal tissues as well as renal and very little hepatobiliary excretion. Nevertheless, the patterns of accumulation of 99mTc-tricine-HYNIC-TOC in tumours and normal organs were comparable to those of 111In-DTPA-OC. A lesion-by-lesion comparison showed comparable tumour detection capabilities in intrahepatic tumour sites and superior capabilities of 99mTc-tricine-HYNIC-TOC in respect of extrahepatic lesions. In conclusion, 99mTc-tricine-HYNIC-TOC shows promise as a tracer for SSTR imaging, given its favourable clinical characteristics (specific and high receptor affinity, good biodistribution, renal excretion, low radiation exposure, high imaging quality, on-demand availability) and cost-effectiveness. 99mTc-tricine-HYNIC-TOC allows earlier diagnosis (10 min-4 h) compared with 111In-DTPA-OC (4-24 h).

68Ga-DOTATATE PET/CT, 99mTc-HYNIC-Octreotide SPECT/CT, and Whole-Body MR Imaging in Detection of Neuroendocrine Tumors: A Prospective Trial

“…The uptake of the two tracers is comparable (12). Because of these characteristics, we chose to evaluate these patients with this modality, thus reducing radiation exposure and scanning time and increasing the accuracy and sensitivity of lesion detection.…”

6-Hydrazinonicotinamide Derivatives as Bifunctional Coupling Agents for 99mTc-Labeling of Small Biomolecules

“…It was found that the coligand has a significant impact on both the tumor accumulation and the biodistribution of 99m Tc complexes. For example, the binary ligand 99m Tc complex [ 99m Tc(HYNIC-TOC)(tricine) 2 ] shows much higher protein binding than the complexes [ 99m Tc(HYNIC-TOC)(EDDA) x ] and [ 99m Tc(HYNIC-TOC)(tricine) (NIC)] [21][22][23][24][25]. The high serum protein binding was also observed for the 99m Tc-labeled DNA oligonucleotides when tricine was used as the coligand [29][30][31].…”

“…Since then, the HYNIC technology has successfully been used for the 99m Tc-labeling of antibodies [3][4][5][6][7][8] and small biomolecules (BMs), including chemotactic peptides [9][10][11][12][13][14][15][16][17][18], somatostatin analogs [19][20][21][22][23][24][25],"stealth" liposomes [26,27], antisense oligonucleotides [28][29][30][31], a folate receptor ligand [32], and polypeptides [32][33][34]. A ternary ligand system (HYNIC, tricine, and trisodium triphenylphosphine-3,3¢,3≤-trisulfonate, TPPTS) has been used for the 99m Tc-labeling of chemotactic peptides [35] and leukotriene B 4 (LTB 4 ) receptor antagonists [36][37][38][39] for imaging infection and inflammation, integrin a v b 3 receptor antagonists for tumor imaging [40], and a glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist for imaging thrombosis [41][42][43][44][45][46]…”

Nuclear imaging of molecular processes in cancer

“…It is thus a very attractive target for the imaging of growing tumors. Several metalbased agents have been developed for the imaging of integrin expression using PET ( 64 Cu) or SPECT ( 99m Tc, 111 In) radionuclides [56][57][58][59][60][61][62][63][64]. All of these agents share a similar design, using the same peptide-based targeting vector-the sequence arginine-glycine-aspartic acid (RGD), which binds avidly to α v β 3 integrins-combined with chelators for radionuclide binding.…”

“…All of these agents share a similar design, using the same peptide-based targeting vector-the sequence arginine-glycine-aspartic acid (RGD), which binds avidly to α v β 3 integrins-combined with chelators for radionuclide binding. In particular, HYNIC-RGD peptide conjugates are used with 99m Tc and DOTA-RGD conjugates are used for the PET isotopes 64 Cu and 98 Ga as well as for 111 In for SPECT. Overall, all these agents show high α v β 3 -positive tumor uptake together with fast blood clearance and renal excretion.…”