99mTc labeled HYNIC-EDDA/tricine-GE11 peptide as a successful tumor targeting agent

Toward the Development of GE11-Based Radioligands for Imaging of Epidermal Growth Factor Receptor-Positive Tumors

“… 13 , 14 However, the bigger part of publications dealing with the development of GE11-based compounds describe effects similar to those observed here, namely, that no or very low affinities to the EGFR were found. 10 , 11 , 17 , 18 This heterogeneous literature situation is mostly justified by the fact that GE11 presumably shows a relevant EGFR affinity only in a multivalent form, as for example, during its discovery by phage display 9 or in the case of GE11-modified dendrimers, polymers, or particle-based systems. 45 − 48 This is confirmed by a recent study that addressed this very question and found an unmeasurably low affinity for the unmodified GE11 monomer of more than 1 mM on different EGFR-positive cell lines (among these, A431, MDA-MB-468, and U87MG cells), while showing a moderate affinity for a GE11 polymer (GE11-modified polyethyleneimine-polyethyleneglycol) of 1900 ± 432 nM.…”

“…In these studies, some consistent features with respect to in vivo pharmacokinetics, tumor uptakes, and organ distribution of the radiotracers were observed: (i) their primarily renal excretion, (ii) relatively low tumor accumulation with resulting low tumor-to-muscle ratios of 3−3.5 within the observation period of 2–4 h post injection, and (iii) an only moderately blockable accumulation ranging from 1 / 3 to about 1 / 2 of the uptake into the tumor, raising doubts about a high EGFR specificity of the radioligands. 10 , 11 , 13 , 14 , 17 At best, the pharmacokinetic characteristics of the radioligands enabled only suboptimal visualization of the corresponding tumors.…”

“…As a result, several groups have reported the development of GE11-based radiotracers over the past five years. Some of these comprised γ emitters such as 99m Tc and 111 In for application in SPECT imaging, − but most of the attempts focused on the development of PET radiotracers comprising β + emitters such as 18 F, 68 Ga, 64 Cu, and 124 I. ,− Although some of the studies only described the synthesis and radiosynthesis of the radioligands without evaluating them in silico , in vitro , or in vivo , several agents were also studied in vivo in tumor-bearing mice. In these studies, some consistent features with respect to in vivo pharmacokinetics, tumor uptakes, and organ distribution of the radiotracers were observed: (i) their primarily renal excretion, (ii) relatively low tumor accumulation with resulting low tumor-to-muscle ratios of 3−3.5 within the observation period of 2–4 h post injection, and (iii) an only moderately blockable accumulation ranging from 1 / 3 to about 1 / 2 of the uptake into the tumor, raising doubts about a high EGFR specificity of the radioligands. ,,,, At best, the pharmacokinetic characteristics of the radioligands enabled only suboptimal visualization of the corresponding tumors.…”

Peptide Based Imaging Agents for HER2 Imaging in Oncology

“…This group was also able to confirm the specificity of the peptide for HER2 by cell-blocking studies using trastuzumab as a blocking agent. 34 Tumor-to-muscle ratios of 2.4 and 3.4 at 1 hour and 4 hours, respectively were obtaining in SKOV-3 tumor bearing mice.…”

Preparation and evaluation of 99mTc-labeled porphyrin complexes prepared using PNP and HYNIC cores: studying the effects of core selection on pharmacokinetics and tumor uptake in a mouse model

“…Radiolabeling of compound (vii) with 99m Tc was carried out by following the generalized procedure usually employed for 99m Tc-labeling of HYNIC-coupled ligands. 31,32 Stock solutions of SnCl 2 (1 mg mL −1 ) and EDDA (ethylenediamine-N,N′diacetic acid, 50 mg mL −1 ) were prepared. Compound (vii) (0.5 mg, 0.478 μmol) was dissolved in PBS (phosphate buffered saline, 0.2 mL) and the resulting solution was transferred to a glass vial containing tricine (20 mg), EDDA (10 mg) and SnCl 2 (100 μg) followed by the addition of freshly eluted 99m TcO 4 − (1 mL, 12 mCi).…”