Evaluation of 99mTc-HYNIC-TMTP1 as a tumor-homing imaging agent targeting metastasis with SPECT

Li, Fēi; Cheng, Teng; Dong, Qingjian; Wei, Rui; Zhang, Zhenzhong; Luo, Danfeng; Ma, Xiangyi; Wang, Shixuan; Gao, Qinglei; Ma, Ding; Zhu, Xiaoyan

doi:10.1016/j.nucmedbio.2014.11.001

Cited by 29 publications

(25 citation statements)

References 31 publications

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“…Except the kidneys, all other normal organs had relatively low uptake of [ 18 F]AlF-NOTA-G-TMTP1. However, the absolute tumors uptake value of [ 18 F] AlF-NOTA-G-TMTP1 was lower than [ 18 F]AlF-NOTA-RGD [28], combined with the cell uptake results, we suspect that it may be due to the much faster blood clearance and less expression of TMTP1 receptors on the cell surface, which was consistent with the previously reported study (21). There are still some ways in which the pharmacokinetics characteristic of the probe may get improved (28,29).…”

Section: Discussionsupporting

confidence: 92%

“…In this study, we conjugated NOTA to TMTP1 via a glycine residue which provided a spacer function to maintain its own activity and improve its excretion kinetics. The lipophilicity of [ 18 F]AlF-NOTA-G-TMTP1 (log P, -3.166 ± 0.022) and 99m Tc labeled TMTP1 (log P, -2.648 ± 0.026) was in the same range (21), but [ 18 F]AlF-NOTA-G-TMTP1 was more hydrophilic than 99m Tc-HYNIC-TMTP1 which decreased the physiological uptake in the liver area. The metastatic potential of HepG2 cell and SMCC-7721 were controversial, some reports suggested HepG2 had a low metastatic phenotype (22,23), while other referred HepG2 with highly metastatic potential (24).…”

Section: Discussionmentioning

confidence: 99%

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Syntheses and preliminary evaluation of [¹⁸F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Zhang

Shi

et al. 2016

Contrast Media & Molecular

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The goal of this study is to evaluate a new (18) F-labeled imaging agent for diagnosing high metastatic (aggressive) hepatocellular carcinoma using positron emission tomography (PET). The new (18) F-labeled imaging agent [(18) F]AlF-NOTA-G-TMTP1 was synthesized and radiolabeled with (18) F using NOTA-AlF chelation method. The tumor-targeting characteristics of [(18) F]AlF-NOTA-G-TMTP1 was assessed in HepG2, SMCC-7721, HCC97L and HCCLM3 xenografts. The total synthesis time was about 20 min with radiochemical yield of 25 ± 6%. The specific activity was about 11.1-14.8 GBq/µmol at the end of synthesis based on the amount of peptide used and the amount of radioactivity trapped on the C18 column. The log P value of [(18) F]AlF-NOTA-G-TMTP1 was -3.166 ± 0.022. [(18) F]AlF-NOTA-G-TMTP1 accumulated in SMCC-7721 and HCCLM3 tumors (high metastatic potential) in vivo and result in tumor/muscle (T/M) ratios of 4.5 ± 0.3 and 4.7 ± 0.2 (n = 4) as measured by PET at 40 min post-injection (p.i.). Meanwhile, the tumor/muscle (T/M) ratios of HepG2 and HCC97L tumors (low metastatic potential) were1.6 ± 0.3 and 1.8 ± 0.4. The tumor uptake of [(18) F]AlF-NOTA-G-TMTP1 could be inhibited 61.9% and 57.6% by unlabeled G-TMTP1 in SMCC-7721 and HCCLM3 xenografts at 40 min p.i., respectively. Furthermore, [(18) F]AlF-NOTA-G-TMTP1 showed pretty low activity in the liver and intestines in all tumor bearing mice, such in vivo distribution pattern would be advantageous for the detection of hepatic carcinoma. Overall, [(18) F]AlF-NOTA-G-TMTP1 may specifically target high metastatic or/and aggressive hepatocellular carcinoma with low background activity and, therefore, holds the potential to be used as an imaging agent for detecting tumor lesions within the liver area. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Syntheses and preliminary evaluation of [¹⁸F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Zhang

Shi

et al. 2016

Contrast Media & Molecular

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“…In contrast, in the peptide-free reaction, after 1 min (Fig. 1c), ~10 % Tc-99m remained at the origin, consistent with the formation of TcO 2 colloid [16]. However, after the 15 min incubation, there was no evidence of colloid (Fig.…”

Section: Resultsmentioning

confidence: 58%

“…Using this solvent, the peptide remains at the origin (rf=0) and Tc0 4 − moves with the solvent front rf 1.0 [16]. Developed strips were imaged with an ITLC reader (BioScan 1000) and the purity calculated using regions of interest drawn in the WINSCAN software (BioScan Inc, Washington DC).…”

Section: Methodsmentioning

confidence: 99%

Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis

et al. 2015

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Purpose Systemic peripheral amyloidosis is a rare disease in which misfolded proteins deposit in various organs. We have previously developed I-124 labeled peptide p5+14 as a tracer for positron emission tomography imaging of amyloid in patients. In this report, we now document the labeling efficiency, bioactivity, and stability of Tc-99m labeled p5+14 for single-photon emission computed tomography (SPECT) imaging of amyloidosis, validated in a mouse model of systemic amyloidosis. Procedures Radiochemical yield, purity, and biological activity of [99mTc]p5+14 were documented by instant thin-layer chromatography (ITLC), SDS-PAGE and a quantitative amyloid fibril pulldown assay. The efficacy and stability were documented in serum amyloid protein A (AA) amyloid-bearing or wild-type (WT) control mice imaged with SPECT/X-ray computed tomography (CT) at two time points. The uptake and retention of [99mTc]p5+14 in hepatosplenic amyloid was evaluated using region of interest (ROI) and tissue counting measurements. Results Tc-99m p5+14 was produced with a radiochemical yield of 75 % with greater than 90 % purity and biological activity comparable to that of radioiodinated peptide. AA amyloid was visualized by SPECT/CT imaging with specific uptake seen in amyloid-laden organs at levels ~5 folds higher than in healthy mice. ROI analyses of decay-corrected SPECT/CT images showed <20 % loss of radiolabel from the 1 to 4 h imaging time points. Biodistribution data confirmed the specificity of the probe accumulation by amyloid-laden organs as compared to non-diseased tissues. Conclusion [99mTc]p5+14 is a specific and stable radiotracer for systemic amyloid in mice and may provide a convenient and inexpensive alternative to imaging of peripheral amyloidosis in patients.

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“…The pentamer TMTP-1 sequence has an affinity for such micro-metastasis (Yang et al, 2008). Furthermore TMTP-1 has been incorporated in polymeric systems assisting in tumorhoming imaging and targeting of anti-tumor peptides both in vitro and in mouse models (Li et al, 2015;Liu et al, 2012;Ma et al, 2012). To assess whether metastatic targeting was retained when the TP was included in the RMHT and RM 3 GT vector design two experiments were completed.…”

Section: Resultsmentioning

confidence: 99%

Development of TMTP-1 targeted designer biopolymers for gene delivery to prostate cancer

McBride

Massey

McCaffrey

et al. 2016

International Journal of Pharmaceutics

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Designer biopolymers (DBPs) represent state of the art genetically engineered biomacromolecules designed to condense plasmid DNA, and overcome intra- and extra- cellular barriers to gene delivery. Three DBPs were synthesized, each with the tumor molecular targeting peptide-1 (TMTP-1) motif to specifically target metastases. Each DBP was complexed with a pEGFP-N1 reporter plasmid to permit physiochemical and biological assay analysis. Results indicated that two of the biopolymers (RMHT and RM3GT) effectively condensed pEGFP-N1 into cationic nanoparticles <100 nm and were capable of transfecting PC-3 metastatic prostate cancer cells. Conversely the anionic RMGT DBP nanoparticles could not transfect PC-3 cells. RMHT and RM3GT nanoparticles were stable in the presence of serum and protected the cargo from degradation. Additionally it was concluded that cell viability could recover post-transfection with these DBPs, which were less toxic than the commercially available transfection reagent Lipofectamine(®) 2000. With both DBPs, a higher transfection efficacy was observed in PC-3 cells than in the moderately metastatic, DU145, and normal, PNT2-C2, cell lines. Blocking of the TMTP-1 receptors inhibited gene transfer indicating internalization via this receptor. In conclusion RMHT and RM3GT are fully functional DBPs that address major obstacles to gene delivery and target metastatic cells expressing the TMTP-1 receptor.

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Evaluation of 99mTc-HYNIC-TMTP1 as a tumor-homing imaging agent targeting metastasis with SPECT

Cited by 29 publications

References 31 publications

Syntheses and preliminary evaluation of [¹⁸F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Syntheses and preliminary evaluation of [¹⁸F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis

Development of TMTP-1 targeted designer biopolymers for gene delivery to prostate cancer

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Evaluation of 99mTc-HYNIC-TMTP1 as a tumor-homing imaging agent targeting metastasis with SPECT

Cited by 29 publications

References 31 publications

Syntheses and preliminary evaluation of [18F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Syntheses and preliminary evaluation of [18F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis

Development of TMTP-1 targeted designer biopolymers for gene delivery to prostate cancer

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Resources

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Syntheses and preliminary evaluation of [¹⁸F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Syntheses and preliminary evaluation of [¹⁸F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma