Novel fluorine-18 labeled 5-(1-pyrrolidinylsulfonyl)-7-azaisatin derivatives as potential PET tracers for in vivo imaging of activated caspases in apoptosis

Waldmann, Christopher M.; Hermann, Sven; Faust, Andreas; Riemann, Burkhard; Schober, Otmar; Schäfers, Michael; Haufe, Günter; Kopka, Klaus

doi:10.1016/j.bmc.2015.07.014

Cited by 9 publications

(9 citation statements)

References 32 publications

(40 reference statements)

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“…When normalized to 125 I-SGMIB-5F7 levels (Fig. 3), tumor uptake of 18 F-RL-I-5F7 was 26–28% higher ( P <0.05) than that of 18 F-SFB-5F7, consistent with the hypothesized effects of charged guanidine (17) and polar triazole (21) moieties in 18 F-RL-I on trapping of labeled catabolites, thereby enhancing tumor uptake. Generally, uptake of the two 18 F-5F7 conjugates in normal tissues was more than an order of magnitude lower than that in tumor, with the exception of renal levels for 18 F-RL-I-5F7, which were comparable to those for 125 I-SGMIB-5F7.…”

Section: Resultssupporting

confidence: 59%

“…A factor that could contribute to the low renal activity levels seen with 18 F-SFB-5F7 is the formation of 4- 18 F-fluorohippuric acid, the primary metabolite reported from other proteins labeled using the 18 F-SFB method (34). On the other hand, the polar triazole (21) and especially the guanidine moieties in 18 F-RL-I might have contributed to its high renal retention as seen with Nanobodies bearing other polar functionalities (24,25). Future studies are planned to determine whether the radioactivity retained in kidneys is due to intact 18 F-RL-I-5F7 or trapping of lower molecular weight catabolites generated by its lysosomal proteolysis (33,35).…”

Section: Discussionmentioning

confidence: 99%

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Preclinical Evaluation of ¹⁸F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET

et al. 2016

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The human growth factor receptor type 2 (HER2) is overexpressed in breast as well as other types of cancer. ImmunoPET, a noninvasive imaging procedure that could assess HER2 status in both primary and metastatic lesions simultaneously, could be a valuable tool for optimizing application of HER2-targeted therapies in individual patients. Herein, we have evaluated the tumor targeting potential of the 5F7 anti-HER2 Nanobody (single-domain antibody fragment; ~13 kDa) after 18F labeling by two methods. Methods The 5F7 Nanobody was labeled with 18F using the novel residualizing label N-succinimidyl 3-((4-(4-18F-fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate (18F-SFBTMGMB; 18F-RL-I) and also via the most commonly utilized 18F protein labeling prosthetic agent, N-succinimidyl 3-18F-fluorobenzoate (18F-SFB). For comparison, 5F7 Nanobody was also labeled using the residualizing radioiodination agent N-succinimidyl 4-guanidinomethyl-3-125I-iodobenzoate (125I-SGMIB). Paired label (18F/125I) internalization assays and biodistribution studies were performed on HER2-expressing BT474M1 breast carcinoma cells and in mice with BT474M1 subcutaneous xenografts, respectively. Micro positron emission tomography/computed tomography (microPET/CT) imaging of 5F7 Nanobody labeled using 18F-RL-I also was performed. Results Internalization assays indicated that intracellularly retained radioactivity for 18F-RL-I-5F7 was similar to that for co-incubated 125I-SGMIB-5F7, while that for 18F-SFB-5F7 was lower than co-incubated 125I-SGMIB-5F7 and decreased with time. BT474M1 tumor uptake of 18F-RL-I-5F7 was 28.97 ± 3.88 %ID/g at 1 h and 36.28 ± 14.10 %ID/g at 2 h, reduced by >90% trastuzumab blocking, indicating HER2-specificity of uptake, and also 26–28% higher (P < 0.05) than that of 18F-SFB-5F7. At 2 h, the tumor-to-blood ratio for 18F-RL-I-5F7 (47.4 ± 13.1) was significantly higher (P < 0.05) than for 18F-SFB-5F7 (25.4 ± 10.3); however, kidney uptake was 28–36-fold higher for 18F-RL-I-5F7. Conclusion 18F-RL-I-5F7 is a promising tracer for evaluating HER2 status by immunoPET; however, in settings where renal background is problematic, strategies for reducing its kidney uptake may be needed.

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Section: Resultssupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of ¹⁸F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET

et al. 2016

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“…Their mechanism of inhibition is believed to involve the formation of a tetrahedral thiohemiketal intermediate after reaction between the electrophilic C-3 carbonyl group of the isatin moiety and the catalytic cysteine residue (Figure 3). Isatin sulfonamide-based PET radiotracers targeting active caspase-3 have been extensively investigated in preclinical studies; a selection is summarised in Table 1 [11,[16][17][18][19][20][21][22][23][24][25][26][27][28]. Although there is one example of a boron-dipyrromethene (abbreviated as BODIPY) attachment, most derivations at the N1 position feature 5/6-membered triazole and phenyl rings.…”

Section: Chemical Design and Radiolabelling Of [ 18 F]icmt-11mentioning

confidence: 99%

“…Isatin sulfonamide-based PET radiotracers targeting active caspase-3 have been extensively investigated in preclinical studies; a selection is summarised in Table 1 [ 11 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Although there is one example of a boron-dipyrromethene (abbreviated as BODIPY) attachment, most derivations at the N1 position feature 5/6-membered triazole and phenyl rings.…”

Section: Chemical Design and Radiolabelling Of [ 18 mentioning

confidence: 99%

Development of [18F]ICMT-11 for Imaging Caspase-3/7 Activity during Therapy-Induced Apoptosis

Garcia-Arguello

Lopez-Lorenzo

Cornelissen

et al. 2020

Cancers

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Insufficient apoptosis is a recognised hallmark of cancer. A strategy to quantitatively measure apoptosis in vivo would be of immense value in both drug discovery and routine patient management. The first irreversible step in the apoptosis cascade is activation of the “executioner” caspase-3 enzyme to commence cleavage of key structural proteins. One strategy to measure caspase-3 activity is Positron Emission Tomography using isatin-5-sulfonamide radiotracers. One such radiotracer is [18F]ICMT-11, which has progressed to clinical application. This review summarises the design and development process for [18F]ICMT-11, suggesting potential avenues for further innovation.

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“…153 In conclusion, [ 18 F]fluoroethyl azide is a useful building block for the fluorine-18 labelling of biomolecules and small Scheme 42 PET tracers synthesised from [ 18 F]fluoroethyl azide in a CuAAC. 55,148,149,151,[156][157][158][159][160]163,164,[166][167][168][169][170][171][172][173][174][175][176][177][178][179][180] 181 Besides introduction of fluorine-18, this building block was employed frequently to increase polarity of the PET tracer and thereby improve its pharmacokinetic properties.…”

confidence: 99%

Fluorine-18 labelled building blocks for PET tracer synthesis

et al. 2017

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Positron emission tomography (PET) is an important driver for present day healthcare. Fluorine-18 is the most widely used radioisotope for PET imaging and a thorough overview of the available radiochemistry methodology is a prerequisite for selection of a synthetic approach for new fluorine-18 labelled PET tracers. These PET tracers can be synthesised either by late-stage radiofluorination, introducing fluorine-18 in the last step of the synthesis, or by a building block approach (also called modular build-up approach), introducing fluorine-18 in a fast and efficient manner in a building block, which is reacted further in one or multiple reaction steps to form the PET tracer. This review presents a comprehensive overview of the synthesis and application of fluorine-18 labelled building blocks since 2010.

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Novel fluorine-18 labeled 5-(1-pyrrolidinylsulfonyl)-7-azaisatin derivatives as potential PET tracers for in vivo imaging of activated caspases in apoptosis

Cited by 9 publications

References 32 publications

Preclinical Evaluation of ¹⁸F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET

Preclinical Evaluation of ¹⁸F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET

Development of [18F]ICMT-11 for Imaging Caspase-3/7 Activity during Therapy-Induced Apoptosis

Fluorine-18 labelled building blocks for PET tracer synthesis

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Novel fluorine-18 labeled 5-(1-pyrrolidinylsulfonyl)-7-azaisatin derivatives as potential PET tracers for in vivo imaging of activated caspases in apoptosis

Cited by 9 publications

References 32 publications

Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET

Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET

Development of [18F]ICMT-11 for Imaging Caspase-3/7 Activity during Therapy-Induced Apoptosis

Fluorine-18 labelled building blocks for PET tracer synthesis

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Preclinical Evaluation of ¹⁸F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET

Preclinical Evaluation of ¹⁸F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET