Synthesis and ex vivo biodistribution of two 68Ga-labeled tetrazine tracers: Comparison of pharmacokinetics

Lambidis, Elisavet; Lumén, Dave; Koskipahta, Elina; Imlimthan, Surachet; Lopez, Brianda B.; Fraguas-Sánchez, Ana Isabel; Sarparanta, Mirkka; Cheng, R. Holland; Airaksinen, Anu J.

doi:10.1016/j.nucmedbio.2022.05.004

Cited by 4 publications

(7 citation statements)

References 49 publications

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“…As expected, 177 Lu-TZ-2 was almost completely excreted (%ID > 98%) from the body at the time of sacrifice (4 h). The rapid clearance of 177 Lu-TZ-2 is similar to other structurally analogous tetrazine-based chaser agents …”

Section: Resultsmentioning

confidence: 70%

“…The rapid clearance of 177 Lu-TZ-2 is similar to other structurally analogous tetrazine-based chaser agents. 38 Our initial pretargeted biodistribution studies were conducted by using NOD SCID mice in an OVCAR-3 ovarian cancer model. A dual-isotope strategy was utilized to examine the simultaneous biodistributions of the 177 Lu-DOTA-TZ probe and 111 In-labeled copolymers.…”

Section: Acs Applied Polymer Materialsmentioning

confidence: 99%

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Exploration of a Pretargeted Theranostic Copolymer Employing Inverse Electron-Demand Diels–Alder Conjugation in Ovarian Cancer

Alshehri,

Rawat,

Basiri

et al. 2023

ACS Appl. Polym. Mater.

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Similar to radioimmunotherapeutics, nanomedicinebased radiotherapeutics are hampered by dose-limiting radiotoxicities due to long blood circulation times. To address this limitation, we explored the pretargeting approach using the inverse electron-demand Diels−Alder (IEDDA) reaction between trans-cyclooctene (TCO) and tetrazine (TZ). Specifically, we synthesized low (22.7 kDa)-and high (93.7−108.7 kDa)-molecular-weight N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers with TCO-incorporated linkers of various lengths in parallel with small-molecule 177 Lu-labeled TZ chaser agents. The IEDDA reaction kinetics between the TCOincorporated copolymer and TZ chaser agents was found to be initially rapid but quickly decreased as copolymer molecular weight increased. The various linkers employed in this study were found to significantly impact IEEDA kinetics but did not yield a clear trend between length and kinetics. The pretargeted system was examined in an OVCAR-3 ovarian cancer mouse model. The tumor uptake of the TCOincorporated copolymers by 76 h ranged from 10 to 14.1%ID/g, but the elevated residual blood retention of the high-molecularweight copolymers led to undesirable IEDDA reaction and retention in the blood compartment. The high off-target blood retention resulted in modest tumor uptake and poor tumor-to-nontarget tissue ratios at 4 h postadministration of the chaser agent. A masking agent (DP-TZ) that reacts with and inactivates TCO moieties in the blood compartment was found to substantially lower the undesirable retention of the 177 Lu-labeled TZ chaser agent in the blood, leading to significant improvements in tumor-to-nontarget ratios.

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Section: Resultsmentioning

confidence: 70%

Section: Acs Applied Polymer Materialsmentioning

confidence: 99%

Exploration of a Pretargeted Theranostic Copolymer Employing Inverse Electron-Demand Diels–Alder Conjugation in Ovarian Cancer

Alshehri,

Rawat,

Basiri

et al. 2023

ACS Appl. Polym. Mater.

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“…The iEDDA reaction between a tetrazine and TCO is known for its bioorthogonality and fast reaction kinetics . The reaction has been successfully applied for radiolabeling of several different types of nanomaterial-based drug delivery systems in mild reaction conditions, − and it is especially well-suited for materials which are sensitive for harsh reaction conditions. Furthermore, the fast reaction kinetics allows its use for labeling with radionuclides with a short physical half-life, such as for fluorine-18 ( t 1/2 = 109.7 min).…”

Section: Resultsmentioning

confidence: 99%

In Vivo Imaging of [60]Fullerene-Based Molecular Spherical Nucleic Acids by Positron Emission Tomography

et al. 2023

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fullerene-based molecular spherical nucleic acids (MSNAs), consisting of a human epidermal growth factor receptor 2 (HER2) mRNA antisense oligonucleotide sequence with a native phosphodiester and phosphorothioate backbone, were synthesized, site-specifically labeled with a positron emitting fluorine-18 and intravenously administrated via tail vein to HER2 expressing HCC1954 tumor-bearing mice. The biodistribution of the MSNAs was monitored in vivo by positron emission tomography/computed tomography (PET/CT) imaging. MSNA with a native phosphodiester backbone (MSNA-PO) was prone to rapid nuclease-mediated degradation, whereas the corresponding phosphorothioate analogue (MSNA-PS) with improved enzymatic stability showed an interesting biodistribution profile in vivo. One hour after the injection, majority of the radioactivity was observed in spleen and liver but also in blood with an average tumor-tomuscle ratio of 2. The prolonged radioactivity in blood circulation may open possibilities to the targeted delivery of the MSNAs.

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“…A range of targeting vectors, such as antibodies ,,, and other nanomedicines ,,, modified with TCO have been radiolabeled in vivo with various radiolabeled tetrazine derivatives to investigate the pretargeting concept. Despite all the benefits of the pretargeting approach, the development of new efficient PET radiotracers is still needed for the adaptation of this multistep strategy to daily clinical use.…”

Section: Introductionmentioning

confidence: 99%

“…13−17 The introduction of a two-step approach not only greatly lowers radiation dose to healthy tissue but also improves PET image contrast by decreasing the background radioactivity in nontarget organs (Figure 1A). 11,18 A range of targeting vectors, such as antibodies 15,17,19,20 and other nanomedicines 7,16,21,22 modified with TCO have been radiolabeled in vivo with various radiolabeled tetrazine derivatives to investigate the pretargeting concept. Despite all the benefits of the pretargeting approach, the development of new efficient PET radiotracers is still needed for the adaptation of this multistep strategy to daily clinical use.…”

Section: ■ Introductionmentioning

confidence: 99%

Tetrazine Glycoconjugate for Pretargeted Positron Emission Tomography Imaging of trans-Cyclooctene-Functionalized Molecular Spherical Nucleic Acids

Auchynnikava,

Äärelä,

Liljenbäck

et al. 2023

ACS Omega

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Synthesis and ex vivo biodistribution of two 68Ga-labeled tetrazine tracers: Comparison of pharmacokinetics

Cited by 4 publications

References 49 publications

Exploration of a Pretargeted Theranostic Copolymer Employing Inverse Electron-Demand Diels–Alder Conjugation in Ovarian Cancer

Exploration of a Pretargeted Theranostic Copolymer Employing Inverse Electron-Demand Diels–Alder Conjugation in Ovarian Cancer

In Vivo Imaging of [60]Fullerene-Based Molecular Spherical Nucleic Acids by Positron Emission Tomography

Tetrazine Glycoconjugate for Pretargeted Positron Emission Tomography Imaging of trans-Cyclooctene-Functionalized Molecular Spherical Nucleic Acids

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