99mTc(CO)3-DTMA bombesin conjugates having high affinity for the GRP receptor

Lane, Stephanie R.; Veerendra, B.; Rold, Tammy L.; Sieckman, Gary L.; Hoffman, Timothy J.; Jurisson, Silvia S.; Smith, Charles J.

doi:10.1016/j.nucmedbio.2007.11.007

Cited by 34 publications

(23 citation statements)

References 41 publications

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“…Authors suggest that an aliphatic tethering group in the -alanine derivative decreases the ability of lysosomal proteases to degrade the peptide. A similar effect of a linker was found by Lane and co-workers [166] for this bombesin analogue labelled with the [ 99m Tc(CO) 3 ] + tridentate 2-(N,N -Bis(tertbutoxycarbonyl)diethylenetriamine) acetic acid (DTMA) chelator. This can be explained by the inability of lysosomal proteases to fragment the aliphatic -Ala linker as compared to the amino acid linkers.…”

Section: Good Retention Of Internalised Radio Activity In Cancer Cellssupporting

confidence: 81%

“…Tumour accumulation one hour after injection in mice bearing PC-3 tumours was lower for a -alanine linker (in spite of the best affinity), presumably due to avid uptake in the liver. A shift to renal excretion by a linker containing polar serine was reported [166] for a 99m Tc(CO) 3 -labelled bombesin conjugate with a 2-(N,N -Bis(tert-butoxycarbonyl) diethylenetriamine) acetic acid (DTMA) chelator. A decrease of liver uptake by the introduction of hydrophilic lysine into the -alanine linker between bombesin and the retro[N -carboxymethylhistidine] chelator was reported by Garayoa et al [123].…”

Section: Rapid Clearance Of Non-reacted Targeting Protein From Blood mentioning

confidence: 96%

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Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

Tolmachev

Orlova

2010

CMC

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Progress in genomics and proteomics provides clinical oncology with new anti-cancer drugs, which target selectively aberrantly expressed membrane proteins and associated signalling pathways in malignant cells. Molecular targeting also enables specific delivery of cytotoxic substances to tumours sparing healthy tissues. Improved selectivity of the treatment reduces side effects and widens the therapeutic window. However, only a part of the patients might benefit from such treatment due to inter- and intrapatient heterogeneity of therapeutic target expression. This makes it necessary to identify patients, who may benefit from targeting therapy. Radiolabelled peptides can provide selective and sensitive detection of molecular therapeutic targets in both primary tumours and metastases in a single non-invasive procedure, making personalised treatment possible. The choice of detection method (single photon emission tomography or positron emission tomography), radionuclide for labelling and labeling chemistry can appreciably influence the imaging property of a tracer. The labelling method might affect the binding affinity, the cellular processing and retention of a radionuclide, the biodistribution of a targeting peptide, and excretion pathways of a non-bound tracer and radiocatabolites. This influences the sensitivity and specificity of the imaging. This influence is exemplified by three classes of tumour-targeting peptides: somatostatin analogues, bombesin analogues and Affibody molecules. The review suggests approaches for selection of an optimal labelling chemistry.

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Section: Good Retention Of Internalised Radio Activity In Cancer Cellssupporting

confidence: 81%

Section: Rapid Clearance Of Non-reacted Targeting Protein From Blood mentioning

confidence: 96%

Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

Tolmachev

Orlova

2010

CMC

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“…SPECT still has a larger installed base of cameras and lower cost than PET, and widespread availability of generator produced 99m Tc, as well as 111 In (17, 18). NODAGA for 64 Cu and 68 Ga, DOTA-MA for 111 In and the diethylenetriamine for “ 99m Tc(CO) 3 ” were chosen as chelators because they form highly stable complexes with these metal ions (21, 22). Imaging studies showed that the thrombus target was clearly visualized by 68 Ga-FBP14 and 111 In-FBP15 in two different animal models with high thrombus-to-background ratios, but that 99m Tc-FBP16 was ineffective.…”

Section: Discussionmentioning

confidence: 99%

Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of ¹¹¹In- and ⁶⁸Ga-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats

et al. 2015

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We recently showed the high target specificity and favorable imaging properties of 64Cu and Al18F positron emission tomography (PET) probes for non-invasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with 68Ga, 111In, or 99mTc as thrombus imaging agents for PET and single-photon emission computed tomography (SPECT). In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in two animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Methods Radiotracers were synthesized using a known fibrin-binding peptide conjugated to NODAGA, DOTA-MA, or a diethylenetriamine ligand (DETA-PA), followed by labeling with 68Ga (FBP14, 68Ga-NODAGA), 111In (FBP15, 111In-DOTA-MA) or 99mTc (FBP16, 99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed 125I-labeled thrombi and with a non-binding control probe using SPECT/PET/CT imaging. Results All three radiotracers showed similar affinity to soluble fibrin fragment DD(E) (Ki = 0.53–0.83 μM). After the kidneys, the highest uptake of 68Ga-FBP14 and 111In-FBP15 was in the thrombus (1.0 ± 0.2% ID/g) with low off-target accumulation. Both radiotracers underwent fast systemic elimination (t1/2 = 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. 99mTc-FBP16 displayed low target uptake and distribution consistent with aggregation and/or degradation. Triple isotope imaging experiments showed that both 68Ga-FBP14 and 111In-FBP15, but not the nonbinding derivative 64Cu-D-Cys-FBP8, detected the location of the 125I-labeled thrombus, confirming high target specificity. Conclusion 68Ga-FBP14 and 111In-FBP15 have high fibrin affinity and thrombus specificity, and represent useful PET and SPECT probes for thrombus detection.

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“…A number of potent BBS analogues have been labeled with various radionuclides, such as 99 m Tc, 111 In, 90 Y, 64 Cu, 177 Lu, 68 Ga, or 18 F, for targeting GRPR-expressing cancer cells in both animal models and human subjects (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Among the available PET nuclides, 18 F has ideal characteristics for peptide receptor imaging studies in terms of its half-life (109.7 min) and low + energy (0.64 MeV) (26).…”

Section: Introductionmentioning

confidence: 99%

In Vitro and in Vivo Characterization of Novel ¹⁸F-Labeled Bombesin Analogues for Targeting GRPR-Positive Tumors

Honer

Becaud

et al. 2010

Bioconjugate Chem.

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The gastrin-releasing peptide receptor (GRPR) is overexpressed on a number of human tumors and has been targeted with radiolabeled bombesin analogues for the diagnosis and therapy of these cancers. Seven bombesin analogues containing various linkers and peptide sequences were designed, synthesized, radiolabeled with (18)F, and characterized in vitro and in vivo as potential PET imaging agents. Binding studies displayed nanomolar binding affinities toward human GRPR for all synthesized bombesin analogues. Two high-affinity peptide candidates 6b (K(i) = 0.7 nM) and 7b (K(i) = 0.1 nM) were chosen for further in vivo evaluation. Both tracers revealed specific uptake in GRPR-expressing PC-3 tumors and the pancreas. Compared to [(18)F]6b, compound [(18)F]7b was characterized by superior tumor uptake, higher specificity of tracer uptake, and more favorable tumor-to-nontarget ratios. In vivo PET imaging allowed for the visualization of PC-3 tumor in nude mice suggesting that [(18)F]7b is a promising PET tracer candidate for the diagnosis of GRPR-positive tumors in humans.

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99mTc(CO)3-DTMA bombesin conjugates having high affinity for the GRP receptor

Cited by 34 publications

References 41 publications

Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of ¹¹¹In- and ⁶⁸Ga-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats

In Vitro and in Vivo Characterization of Novel ¹⁸F-Labeled Bombesin Analogues for Targeting GRPR-Positive Tumors

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99mTc(CO)3-DTMA bombesin conjugates having high affinity for the GRP receptor

Cited by 34 publications

References 41 publications

Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of 111In- and 68Ga-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats

In Vitro and in Vivo Characterization of Novel 18F-Labeled Bombesin Analogues for Targeting GRPR-Positive Tumors

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Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of ¹¹¹In- and ⁶⁸Ga-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats

In Vitro and in Vivo Characterization of Novel ¹⁸F-Labeled Bombesin Analogues for Targeting GRPR-Positive Tumors