99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours: first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives

Abstract

[111In-diethylene triamine penta-acetic acid-D-Phe1]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary excretion was lower compared with the 111In derivatives. Semi-quantitative region of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99mTc images. We conclude that 99mTcEDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111In-labelled octreotide derivatives.

The utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for assessment of lung lesions in patients with neuroendocrine tumors

“…Semiquantitative results in our study confirm previously reported higher T/NT ratios on SPECT than whole body images [9,15]. As expected, therefore, SPECT should be preferred over whole body scintigraphy as it can more precisely detect and localize focal lung lesions.…”

“…Mecke and Behe introduced hydrasinonicotinamide (HYNIC) as a bifunctional chelator for 99m Tc labeling of octreotide and Tyr 3 -octreotide (TOC) with high efficiency [8]. Decristoforo and co-workers reported favorable clinical characteristics of HYNIC when ethylene diamine diacetic acid (EDDA) was used as a co-ligand, thereby introducing 99m Tc-EDDA/HYNIC-TOC somatostatin analogue to clinical practice [9]. Recent investigations indicated a potential value of 99m Tc-EDDA/HYNIC-TOC for evaluating malignant tumors that express SSTRs, especially subtype 2, but indicated the need for further investigations [10,11].…”

The influence of Ki-67 proliferation index on Tc-99m-EDDA-HYNIC-TOC somatostatin receptor scintigraphy in patients with carcinoids

“…However, poor physical properties of In-111 have triggered intense efforts to synthesize somatostatin analogues which can be labeled with Tc-99m, for the purpose of achieving better image quality, smaller expositional radiation doses per patient, and ready availability [29,30]. This is how octreotide derivates which can be labeled with Tc-99m-pertechnetate were synthesized, including Tc-99m-Na-(hydroxynitrile)-Tyr3-octreotide (HYNIC-TOC, Tectrotyd), which yields excellent image quality in NET patients [31][32][33][34][35]. Comparative studies have shown that HYNIC-TOC labeled with Tc-99m ensures a better detection of lesions in comparison to In-111-Octreotide, and also that it decreases the chances of false positive findings [31,32].…”

“…This is how octreotide derivates which can be labeled with Tc-99m-pertechnetate were synthesized, including Tc-99m-Na-(hydroxynitrile)-Tyr3-octreotide (HYNIC-TOC, Tectrotyd), which yields excellent image quality in NET patients [31][32][33][34][35]. Comparative studies have shown that HYNIC-TOC labeled with Tc-99m ensures a better detection of lesions in comparison to In-111-Octreotide, and also that it decreases the chances of false positive findings [31,32]. Apart from the appropriate pharmacokinetics, better spatial resolution and availability, the advantage of Tc-99m labeled somatostatin analogue is the imaging which can be finished over the course of one day, which makes this radiopharmaceutical suitable for routine use.…”

99mTc-EDDA/HYNIC-TOC in management of patients with head and neck somatostatin receptor positive tumors

“…Technetium-99m ( 99m Tc) labeled hydrazinonicotinyl-Tyr3-octreotide (EDDA/HYNIC-TOC, Tektrotyd) has advantages of short half-life, lower radiation burden; so higher dosage can be administered producing better image quality. Physical characteristics of 99m Tc are more suited for gamma cameras and single photon emission computed tomography (SPECT) imaging [10][11][12]. 99m Tc labeled EDDA/HYNIC-TOC is also a good alternative to Gallium-68 radiotracers ( Tc-EDDA/HYNIC-TOC is the promising method [13][14][15].…”