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( A ) Pharmacokinetic profiles of SPD1 [10 mg/kg, intravenously (iv)] and SPD2 (10 mg/kg, iv) in healthy mice. Plasma concentrations were determined via PpIX fluorescence, and pharmacokinetic parameters were calculated using <t>PKSolver</t> 2.0 software. Data are expressed as means ± SD ( n = 3). ( B ) Blood Gd 3+ levels measured by ICP-MS in orthotopic Hepa1-6 tumor-bearing mice after Gd-DOTA-N 3 administration (0.1 mmol/kg, iv), with or without 6 hours pretreatment with SPD1 or SPD2 (10 mg/kg, iv). ( C ) Ex vivo fluorescence (FL) images of the tumors (T), heart (H), liver (Li), spleen (Sp), lung (Lu), kidney (K), and intestine (I), at indicated time points following SPD1 injection (10 mg/kg, iv) in orthotopic Hepa1-6 tumor-bearing mice. Red dashed circles indicate tumors. Representative images from three mice per time point are shown. ( D ) Quantification of the fluorescence intensity in tumor and major organs of (C). ( E ) Representative micrographs demonstrate H&E staining, GPC3 IHC, and TUNEL staining in orthotopic Hepa1-6 tumor specimens from C57BL/6 mice treated with the following regimens: SPD1 pretreatment followed by Gd-DOTA-N 3 6 hours later, SPD2 pretreatment followed by Gd-DOTA-N 3 6 hours later, Gd-DOTA-N 3 alone, and Gd-DOTA alone. Representative images are shown from three biologically independent experiments. Scale bars, 100 μm. ( F ) Schematic illustration of the molecular imaging mechanism of the SPD1+Gd-DOTA-N 3 probe, highlighting self-assembly into nanofibers and signal amplification via r 1 enhancement. d, days. ( G ) In vivo T 1 -weighted images of subcutaneous Hepa1-6 tumor-bearing mice at multiple time points under four different experimental protocols. Red circles mark tumor regions. Representative images from three mice per group are shown. ( H ) In vivo T 1 -weighted images of orthotopic Hepa1-6 tumor-bearing mice under four different treatment protocols. Red circles mark tumor regions. Representative images from three mice per group are shown.
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( A ) Pharmacokinetic profiles of SPD1 [10 mg/kg, intravenously (iv)] and SPD2 (10 mg/kg, iv) in healthy mice. Plasma concentrations were determined via PpIX fluorescence, and pharmacokinetic parameters were calculated using <t>PKSolver</t> 2.0 software. Data are expressed as means ± SD ( n = 3). ( B ) Blood Gd 3+ levels measured by ICP-MS in orthotopic Hepa1-6 tumor-bearing mice after Gd-DOTA-N 3 administration (0.1 mmol/kg, iv), with or without 6 hours pretreatment with SPD1 or SPD2 (10 mg/kg, iv). ( C ) Ex vivo fluorescence (FL) images of the tumors (T), heart (H), liver (Li), spleen (Sp), lung (Lu), kidney (K), and intestine (I), at indicated time points following SPD1 injection (10 mg/kg, iv) in orthotopic Hepa1-6 tumor-bearing mice. Red dashed circles indicate tumors. Representative images from three mice per time point are shown. ( D ) Quantification of the fluorescence intensity in tumor and major organs of (C). ( E ) Representative micrographs demonstrate H&E staining, GPC3 IHC, and TUNEL staining in orthotopic Hepa1-6 tumor specimens from C57BL/6 mice treated with the following regimens: SPD1 pretreatment followed by Gd-DOTA-N 3 6 hours later, SPD2 pretreatment followed by Gd-DOTA-N 3 6 hours later, Gd-DOTA-N 3 alone, and Gd-DOTA alone. Representative images are shown from three biologically independent experiments. Scale bars, 100 μm. ( F ) Schematic illustration of the molecular imaging mechanism of the SPD1+Gd-DOTA-N 3 probe, highlighting self-assembly into nanofibers and signal amplification via r 1 enhancement. d, days. ( G ) In vivo T 1 -weighted images of subcutaneous Hepa1-6 tumor-bearing mice at multiple time points under four different experimental protocols. Red circles mark tumor regions. Representative images from three mice per group are shown. ( H ) In vivo T 1 -weighted images of orthotopic Hepa1-6 tumor-bearing mice under four different treatment protocols. Red circles mark tumor regions. Representative images from three mice per group are shown.
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( A ) Pharmacokinetic profiles of SPD1 [10 mg/kg, intravenously (iv)] and SPD2 (10 mg/kg, iv) in healthy mice. Plasma concentrations were determined via PpIX fluorescence, and pharmacokinetic parameters were calculated using <t>PKSolver</t> 2.0 software. Data are expressed as means ± SD ( n = 3). ( B ) Blood Gd 3+ levels measured by ICP-MS in orthotopic Hepa1-6 tumor-bearing mice after Gd-DOTA-N 3 administration (0.1 mmol/kg, iv), with or without 6 hours pretreatment with SPD1 or SPD2 (10 mg/kg, iv). ( C ) Ex vivo fluorescence (FL) images of the tumors (T), heart (H), liver (Li), spleen (Sp), lung (Lu), kidney (K), and intestine (I), at indicated time points following SPD1 injection (10 mg/kg, iv) in orthotopic Hepa1-6 tumor-bearing mice. Red dashed circles indicate tumors. Representative images from three mice per time point are shown. ( D ) Quantification of the fluorescence intensity in tumor and major organs of (C). ( E ) Representative micrographs demonstrate H&E staining, GPC3 IHC, and TUNEL staining in orthotopic Hepa1-6 tumor specimens from C57BL/6 mice treated with the following regimens: SPD1 pretreatment followed by Gd-DOTA-N 3 6 hours later, SPD2 pretreatment followed by Gd-DOTA-N 3 6 hours later, Gd-DOTA-N 3 alone, and Gd-DOTA alone. Representative images are shown from three biologically independent experiments. Scale bars, 100 μm. ( F ) Schematic illustration of the molecular imaging mechanism of the SPD1+Gd-DOTA-N 3 probe, highlighting self-assembly into nanofibers and signal amplification via r 1 enhancement. d, days. ( G ) In vivo T 1 -weighted images of subcutaneous Hepa1-6 tumor-bearing mice at multiple time points under four different experimental protocols. Red circles mark tumor regions. Representative images from three mice per group are shown. ( H ) In vivo T 1 -weighted images of orthotopic Hepa1-6 tumor-bearing mice under four different treatment protocols. Red circles mark tumor regions. Representative images from three mice per group are shown.
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( A ) Pharmacokinetic profiles of SPD1 [10 mg/kg, intravenously (iv)] and SPD2 (10 mg/kg, iv) in healthy mice. Plasma concentrations were determined via PpIX fluorescence, and pharmacokinetic parameters were calculated using <t>PKSolver</t> 2.0 software. Data are expressed as means ± SD ( n = 3). ( B ) Blood Gd 3+ levels measured by ICP-MS in orthotopic Hepa1-6 tumor-bearing mice after Gd-DOTA-N 3 administration (0.1 mmol/kg, iv), with or without 6 hours pretreatment with SPD1 or SPD2 (10 mg/kg, iv). ( C ) Ex vivo fluorescence (FL) images of the tumors (T), heart (H), liver (Li), spleen (Sp), lung (Lu), kidney (K), and intestine (I), at indicated time points following SPD1 injection (10 mg/kg, iv) in orthotopic Hepa1-6 tumor-bearing mice. Red dashed circles indicate tumors. Representative images from three mice per time point are shown. ( D ) Quantification of the fluorescence intensity in tumor and major organs of (C). ( E ) Representative micrographs demonstrate H&E staining, GPC3 IHC, and TUNEL staining in orthotopic Hepa1-6 tumor specimens from C57BL/6 mice treated with the following regimens: SPD1 pretreatment followed by Gd-DOTA-N 3 6 hours later, SPD2 pretreatment followed by Gd-DOTA-N 3 6 hours later, Gd-DOTA-N 3 alone, and Gd-DOTA alone. Representative images are shown from three biologically independent experiments. Scale bars, 100 μm. ( F ) Schematic illustration of the molecular imaging mechanism of the SPD1+Gd-DOTA-N 3 probe, highlighting self-assembly into nanofibers and signal amplification via r 1 enhancement. d, days. ( G ) In vivo T 1 -weighted images of subcutaneous Hepa1-6 tumor-bearing mice at multiple time points under four different experimental protocols. Red circles mark tumor regions. Representative images from three mice per group are shown. ( H ) In vivo T 1 -weighted images of orthotopic Hepa1-6 tumor-bearing mice under four different treatment protocols. Red circles mark tumor regions. Representative images from three mice per group are shown.
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( A ) Pharmacokinetic profiles of SPD1 [10 mg/kg, intravenously (iv)] and SPD2 (10 mg/kg, iv) in healthy mice. Plasma concentrations were determined via PpIX fluorescence, and pharmacokinetic parameters were calculated using <t>PKSolver</t> 2.0 software. Data are expressed as means ± SD ( n = 3). ( B ) Blood Gd 3+ levels measured by ICP-MS in orthotopic Hepa1-6 tumor-bearing mice after Gd-DOTA-N 3 administration (0.1 mmol/kg, iv), with or without 6 hours pretreatment with SPD1 or SPD2 (10 mg/kg, iv). ( C ) Ex vivo fluorescence (FL) images of the tumors (T), heart (H), liver (Li), spleen (Sp), lung (Lu), kidney (K), and intestine (I), at indicated time points following SPD1 injection (10 mg/kg, iv) in orthotopic Hepa1-6 tumor-bearing mice. Red dashed circles indicate tumors. Representative images from three mice per time point are shown. ( D ) Quantification of the fluorescence intensity in tumor and major organs of (C). ( E ) Representative micrographs demonstrate H&E staining, GPC3 IHC, and TUNEL staining in orthotopic Hepa1-6 tumor specimens from C57BL/6 mice treated with the following regimens: SPD1 pretreatment followed by Gd-DOTA-N 3 6 hours later, SPD2 pretreatment followed by Gd-DOTA-N 3 6 hours later, Gd-DOTA-N 3 alone, and Gd-DOTA alone. Representative images are shown from three biologically independent experiments. Scale bars, 100 μm. ( F ) Schematic illustration of the molecular imaging mechanism of the SPD1+Gd-DOTA-N 3 probe, highlighting self-assembly into nanofibers and signal amplification via r 1 enhancement. d, days. ( G ) In vivo T 1 -weighted images of subcutaneous Hepa1-6 tumor-bearing mice at multiple time points under four different experimental protocols. Red circles mark tumor regions. Representative images from three mice per group are shown. ( H ) In vivo T 1 -weighted images of orthotopic Hepa1-6 tumor-bearing mice under four different treatment protocols. Red circles mark tumor regions. Representative images from three mice per group are shown.
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( A ) Pharmacokinetic profiles of SPD1 [10 mg/kg, intravenously (iv)] and SPD2 (10 mg/kg, iv) in healthy mice. Plasma concentrations were determined via PpIX fluorescence, and pharmacokinetic parameters were calculated using <t>PKSolver</t> 2.0 software. Data are expressed as means ± SD ( n = 3). ( B ) Blood Gd 3+ levels measured by ICP-MS in orthotopic Hepa1-6 tumor-bearing mice after Gd-DOTA-N 3 administration (0.1 mmol/kg, iv), with or without 6 hours pretreatment with SPD1 or SPD2 (10 mg/kg, iv). ( C ) Ex vivo fluorescence (FL) images of the tumors (T), heart (H), liver (Li), spleen (Sp), lung (Lu), kidney (K), and intestine (I), at indicated time points following SPD1 injection (10 mg/kg, iv) in orthotopic Hepa1-6 tumor-bearing mice. Red dashed circles indicate tumors. Representative images from three mice per time point are shown. ( D ) Quantification of the fluorescence intensity in tumor and major organs of (C). ( E ) Representative micrographs demonstrate H&E staining, GPC3 IHC, and TUNEL staining in orthotopic Hepa1-6 tumor specimens from C57BL/6 mice treated with the following regimens: SPD1 pretreatment followed by Gd-DOTA-N 3 6 hours later, SPD2 pretreatment followed by Gd-DOTA-N 3 6 hours later, Gd-DOTA-N 3 alone, and Gd-DOTA alone. Representative images are shown from three biologically independent experiments. Scale bars, 100 μm. ( F ) Schematic illustration of the molecular imaging mechanism of the SPD1+Gd-DOTA-N 3 probe, highlighting self-assembly into nanofibers and signal amplification via r 1 enhancement. d, days. ( G ) In vivo T 1 -weighted images of subcutaneous Hepa1-6 tumor-bearing mice at multiple time points under four different experimental protocols. Red circles mark tumor regions. Representative images from three mice per group are shown. ( H ) In vivo T 1 -weighted images of orthotopic Hepa1-6 tumor-bearing mice under four different treatment protocols. Red circles mark tumor regions. Representative images from three mice per group are shown.
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( A ) Pharmacokinetic profiles of SPD1 [10 mg/kg, intravenously (iv)] and SPD2 (10 mg/kg, iv) in healthy mice. Plasma concentrations were determined via PpIX fluorescence, and pharmacokinetic parameters were calculated using PKSolver 2.0 software. Data are expressed as means ± SD ( n = 3). ( B ) Blood Gd 3+ levels measured by ICP-MS in orthotopic Hepa1-6 tumor-bearing mice after Gd-DOTA-N 3 administration (0.1 mmol/kg, iv), with or without 6 hours pretreatment with SPD1 or SPD2 (10 mg/kg, iv). ( C ) Ex vivo fluorescence (FL) images of the tumors (T), heart (H), liver (Li), spleen (Sp), lung (Lu), kidney (K), and intestine (I), at indicated time points following SPD1 injection (10 mg/kg, iv) in orthotopic Hepa1-6 tumor-bearing mice. Red dashed circles indicate tumors. Representative images from three mice per time point are shown. ( D ) Quantification of the fluorescence intensity in tumor and major organs of (C). ( E ) Representative micrographs demonstrate H&E staining, GPC3 IHC, and TUNEL staining in orthotopic Hepa1-6 tumor specimens from C57BL/6 mice treated with the following regimens: SPD1 pretreatment followed by Gd-DOTA-N 3 6 hours later, SPD2 pretreatment followed by Gd-DOTA-N 3 6 hours later, Gd-DOTA-N 3 alone, and Gd-DOTA alone. Representative images are shown from three biologically independent experiments. Scale bars, 100 μm. ( F ) Schematic illustration of the molecular imaging mechanism of the SPD1+Gd-DOTA-N 3 probe, highlighting self-assembly into nanofibers and signal amplification via r 1 enhancement. d, days. ( G ) In vivo T 1 -weighted images of subcutaneous Hepa1-6 tumor-bearing mice at multiple time points under four different experimental protocols. Red circles mark tumor regions. Representative images from three mice per group are shown. ( H ) In vivo T 1 -weighted images of orthotopic Hepa1-6 tumor-bearing mice under four different treatment protocols. Red circles mark tumor regions. Representative images from three mice per group are shown.

Journal: Science Advances

Article Title: In vivo membrane engineering traps Gd-based MRI contrast agents for detecting microhepatocellular carcinoma

doi: 10.1126/sciadv.aec9913

Figure Lengend Snippet: ( A ) Pharmacokinetic profiles of SPD1 [10 mg/kg, intravenously (iv)] and SPD2 (10 mg/kg, iv) in healthy mice. Plasma concentrations were determined via PpIX fluorescence, and pharmacokinetic parameters were calculated using PKSolver 2.0 software. Data are expressed as means ± SD ( n = 3). ( B ) Blood Gd 3+ levels measured by ICP-MS in orthotopic Hepa1-6 tumor-bearing mice after Gd-DOTA-N 3 administration (0.1 mmol/kg, iv), with or without 6 hours pretreatment with SPD1 or SPD2 (10 mg/kg, iv). ( C ) Ex vivo fluorescence (FL) images of the tumors (T), heart (H), liver (Li), spleen (Sp), lung (Lu), kidney (K), and intestine (I), at indicated time points following SPD1 injection (10 mg/kg, iv) in orthotopic Hepa1-6 tumor-bearing mice. Red dashed circles indicate tumors. Representative images from three mice per time point are shown. ( D ) Quantification of the fluorescence intensity in tumor and major organs of (C). ( E ) Representative micrographs demonstrate H&E staining, GPC3 IHC, and TUNEL staining in orthotopic Hepa1-6 tumor specimens from C57BL/6 mice treated with the following regimens: SPD1 pretreatment followed by Gd-DOTA-N 3 6 hours later, SPD2 pretreatment followed by Gd-DOTA-N 3 6 hours later, Gd-DOTA-N 3 alone, and Gd-DOTA alone. Representative images are shown from three biologically independent experiments. Scale bars, 100 μm. ( F ) Schematic illustration of the molecular imaging mechanism of the SPD1+Gd-DOTA-N 3 probe, highlighting self-assembly into nanofibers and signal amplification via r 1 enhancement. d, days. ( G ) In vivo T 1 -weighted images of subcutaneous Hepa1-6 tumor-bearing mice at multiple time points under four different experimental protocols. Red circles mark tumor regions. Representative images from three mice per group are shown. ( H ) In vivo T 1 -weighted images of orthotopic Hepa1-6 tumor-bearing mice under four different treatment protocols. Red circles mark tumor regions. Representative images from three mice per group are shown.

Article Snippet: A standard fluorescence-concentration calibration curve was constructed, and the plasma concentration-time profiles were fitted using noncompartmental analysis with PKSolver (v2.0, China Pharmaceutical University, Nanjing, China).

Techniques: Clinical Proteomics, Fluorescence, Software, Ex Vivo, Injection, Staining, TUNEL Assay, Imaging, Amplification, In Vivo