A^99mTc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors

Abstract

In this study, a new neurotensin (NT) analog was labeled with (99m) Tc via HYNIC chelator and tricine as coligand and investigated further. An NT (7-13) analog was prepared, and labeling with (99m) Tc was performed. The internalization rate and biodistribution of radiopeptide were studied in HT-29 cells and nude mice bearing tumor, respectively. Radiolabeling with (99m) Tc was performed at high specific activities (54 MBq/nmol) with an acceptable labeling yield (>95%). In vitro cell line studies showed a specific internalization uptake up to 13.23 ± 0.45% during 4 h which was blocked in the presence of excess cold peptide to 0.83 ± 0.15%. In biodistribution studies, uptake was observed in NT receptor-positive organs so that after 1 h the uptakes in mouse intestine and tumor were 1.23 ± 0.16% ID/g and 1.12 ± 0.11% ID/g, respectively. In animals co-injected with excess cold peptide, reduction uptake in tumor and intestines were 73% (1.10% vs. 0.29% ID/g at 4 h) and 61% (1.22% vs. 0.47% ID/g at 4 h) respectively. Predominant renal excretion pathway with a highest accumulation of activity in bladder was observed for this radiopeptide. This radiolabeled peptide could be a candidate for detection of NT positive tumors.

99mTc-radiolabeled GE11-modified peptide for ovarian tumor targeting

“…Plasma samples were then treated with 500 μl of a mixture of acetonitrile and ethanol (1:1), centrifuged (14,000 rpm, 6 min), filtered (0.22 μm) and degradation of the radiolabeled peptide was assessed in supernatant by RP-HPLC [24]. …”

Radiopharmaceuticals for imaging and endoradiotherapy of neurotensin receptor‐positive tumors

“…Biodistribution was determined in healthy mice, showing predominantly renal excretion along with remarkable liver and intestinal uptake for both radiotracers . Another HYNIC‐bearing NT(8–13) analog with an additional glycine at the N‐terminus and the Lys‐for‐Arg 9 and D‐Tyr‐for‐Tyr 11 exchanges was reported (entry 21, Table ) . In HT29 tumor‐bearing mice, the tumor uptake of the 99m Tc‐labeled peptide was 0.6 to 1.1 and 0.3 to 1.1%ID/g 1 and 4 hours after tracer injection, respectively.…”

New neurotensin analogue radiolabeled by 99m‐technetium as a potential agent for tumor identification

“…However, an appropriate candidate was not yet discovered. [10,22,33,34] According to this result, we were encouraged to evaluate a new analogue of NT for tumor imaging. In the present study, we evaluate a new HYNIC-coupled NT analogue with a modified structure for pancreatic tumor imaging.…”

“…labeled a novel neurotensin analogue with 99m Tc-HYNIC through two different coligand system, namely tricine [34] and tricine/EDDA. [37] Tumor-to-non-target ratios of their analogue for tricine containing radiopeptide are lower than the ratios of our analogue, but ratios for tricine/EDDA containing radiopeptide are within the same range It is important to note that the tumor uptake of biomolecules is a complex phenomenon and not only impacted by biomolecules characteristic.…”