Development of 68Ga labeled human serum albumin for blood pool imaging: a comparison between two ligands

Jain, Akanksha; Pandey, Usha; Gamre, Naresh; Sarma, Haladhar Dev; Dash, Ashutosh

doi:10.1007/s10967-017-5320-0

Cited by 9 publications

(12 citation statements)

References 26 publications

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“…It has been reported previously that higher DOF of HSA with a bifunctional chelator may alter the intrinsic properties of the HSA molecule resulting in higher accumulation in the liver. 22 Our results also showed higher accumulation of activity in the liver compared to blood with an increase in DOF. Additionally, conventional 99m Tc-HSA showed low whole blood activity and high liver uptake.…”

Section: Molecular Pharmaceuticssupporting

confidence: 69%

“…For imaging purpose, HSA has also been labeled with several radioisotopes including 68 Ga, , 18 F, − 125 I, and 99m Tc through diverse bifunctional chelators. Compared with other radioisotopes, 99m Tc is widely used in nuclear medicine because of its optimum photon energy ( t 1/2 = 6 h, E γ = 140 keV) for SPECT imaging, low cost, and its widespread availability from commercial generator system .…”

Section: Discussionmentioning

confidence: 99%

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Development of ^99mTc-Labeled Human Serum Albumin with Prolonged Circulation by Chelate-then-Click Approach: A Potential Blood Pool Imaging Agent

et al. 2019

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Technetium-99m-labeled human serum albumin (99mTc-HSA) has been utilized as a blood pool imaging agent in the clinic for several decades. However, 99mTc-HSA has a short circulation time, which is a critical shortcoming for a blood pool imaging agent. Herein, we developed a novel 99mTc-labeled HSA with a long circulation time using click chemistry and a chelator, 2,2′-dipicolylamine (DPA), (99mTc-DPA-HSA). Specifically, we examined the feasibility of copper-free strain-promoted alkyne-azide cycloaddition (SPAAC) for the incorporation of HSA to the [99mTc (CO)3(H2O)3]+ system by adopting a chelate-then-click approach. In this strategy, a potent chelate system, azide-functionalized DPA, was first complexed with [99mTc (CO)3(H2O)3]+, followed by the SPAAC click reaction with azadibenzocyclooctyne-functionalized HSA (ADIBO–HSA) under biocompatible conditions. Radiolabeling efficiency of azide-functionalized DPA (99mTc-DPA) was >98%. Click conjugation efficiency of 99mTc-DPA with ADIBO–HSA was between 76 and 99% depending on the number of ADIBO moieties attached to HSA. In whole-body in vivo single photon emission computed tomography images, the blood pool uptakes of 99mTc-DPA-HSA were significantly enhanced compared to those of 99mTc-HSA at 10 min, 2, and 6 h after the injection (P < 0.001, 0.025, and 0.003, respectively). Furthermore, the blood activities of 99mTc-DPA-HSA were 8 times higher at 30 min and 10 times higher at 3 h after the injection compared to those of conventional 99mTc-HSA in ex vivo biodistribution experiment. The results exhibit the potential of 99mTc-DPA-HSA as a blood pool imaging agent and further illustrate the promise of the pre-labeling SPAAC approach for conjugation of heat-sensitive biological targeting vectors with [99mTc (CO)3(H2O)3]+.

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Section: Molecular Pharmaceuticssupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Development of ^99mTc-Labeled Human Serum Albumin with Prolonged Circulation by Chelate-then-Click Approach: A Potential Blood Pool Imaging Agent

et al. 2019

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“…Similarly, in one study, indocyanine green (ICG) dye was conjugated after disulfide bond cleavage of HSA (HSA-ICG), and the HSA-ICG showed a limited circulation half-life (2.8 h) with a high liver uptake 43. However, recent labeling methods without using reducing agent showed a longer circulation half-life (4.8 h) 16, 17. Therefore, using a reducing agent to albumin may alter the surface chemistry of albumin and cause an immune response that decreases the circulation time.…”

Section: Resultsmentioning

confidence: 99%

“…For example, 99m Tc-labeled HSA has a very short circulation half-life (32 minutes), and has been applied clinically for several decades 13-15. Other albumin nanoplatforms with a longer circulation half-life (4.8 h) have been reported 16, 17. However, it has yet to be evaluated which factor is affecting or how to control the distribution of the albumin nanoplatforms.…”

Section: Introductionmentioning

confidence: 99%

Versatile and Finely Tuned Albumin Nanoplatform based on Click Chemistry

Park¹,

Song²,

Kim³

et al. 2019

Theranostics

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Albumin is one of the most attractive nanoplatforms for targeted imaging and drug delivery due to its biocompatibility and long circulation half-life. However, previously reported albumin-based nanoplatforms have shown inconsistent blood circulation half-life according to the modified methods, and the affecting factors were not well evaluated, which could hamper the clinical translation of albumin-based nanoplatforms. Herein, we developed a finely tuned click-chemistry based albumin nanoplatform (CAN) with a longer circulation half-life and an efficient tumor targeting ability. Methods: CAN was synthesized in two steps. First, albumin was conjugated with ADIBO-NHS (albumin-ADIBO) by reacting albumin with various molar ratios of ADIBO. The number of attached ADIBO moieties was determined using matrix-assisted laser desorption ionization time of flight (MALDI-TOF). Second, the desired modalities including azide-functionalized chelator, a fluorescence dye, and folate were incorporated into albumin-ADIBO using strain-promoted alkyne-azide cycloaddition reaction (SPAAC reaction). The biodistribution and targeting efficiency of functionalized CANs were demonstrated in mice. Results: The degree of functionalization (DOF) and resulting in vivo biodistribution was controlled precisely using the click chemistry approach. Specifically, the numbers of attached azadibenzocyclooctyne (ADIBO) moieties on albumin, the DOF, were optimized by reacting albumin with varying molar ratios of ADIBO with a high reproducibility. Furthermore, we developed a simple and efficient method to estimate the DOF using UV - visible spectrophotometry (UV-vis), which was further validated by matrix-assisted laser desorption ionization time of flight (MALDI-TOF). The biodistribution of CAN could be controlled by DOF, and CAN with an optimized DOF showed a long circulation half-life (> 18 h). CAN was further functionalized using a simple click chemistry reaction with an azide functionalized chelator, a fluorescence dye, and folate. 64 Cu- and folate-labeled CAN ( 64 Cu-CAN-FA) showed effective and specific folate receptor targeting in vivo , with an over two-fold higher uptake than the liver at 24 h post-injection. Conclusions: Our development from the precisely controlled DOF demonstrates that an optimized CAN can be used as a multifunctional nanoplatform to obtain a longer half-life with radioisotopes and ligands, and provides an effective method for the development of albumin-based tumor theranostic agents.

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“…Blood pool imaging by positron emission tomography (PET) and single photon emission computed tomography (SPECT) have been used for the investigation of infection, 1 gastrointestinal bleeding, 2 cardiac function, [3][4][5] and to measure changes in vascularity and perfusion of tumors and organs. 6,7 Radiolabeled small molecules and blood proteins (such as human serum albumin (HSA)) have been widely used for this purpose, [8][9][10] but radiolabeled erythrocytes in particular have been demonstrated to have numerous applications in nuclear medicine. [11][12][13] Such uses include measurement of total erythrocyte volume and erythrocyte survival time, identification of sites of erythrocyte destruction, selective spleen imaging with damaged erythrocytes, and general blood pool imaging (BPI) studies.…”

Section: Introductionmentioning

confidence: 99%

Automated synthesis of [⁶⁸Ga]oxine, improved preparation of⁶⁸Ga-labeled erythrocytes for blood-pool imaging, and preclinical evaluation in rodents

et al. 2018

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Radiolabeled erythrocytes have multiple applications in nuclear medicine, including blood pool imaging. Historically they have been labeled with SPECT radionuclides. A PET blood pool imaging agent is highly desirable as it would improve clinical applications with better image quality and resolution, higher sensitivity, and dynamic scanning capabilities. With the coming of age of modern Ge/Ga generator systems, gallium-68 is now widely accessible. In this paper we describe an updated method for the preparation of Ga-labeled erythrocytes and their preliminary use in rodent blood pool imaging. A novel automated synthesis of [Ga]oxine using a Ga/Ge generator and automated synthesis module is reported. [Ga]Oxine was synthesized in 50 ± 5% ( = 3) non-decay corrected radiochemical yield and >99% radiochemical purity. Rat and human erythrocytes were successfully labeled with the complex in 42% RCY, and the Ga-labeled erythrocytes have been shown to clearly image the blood pool in a healthy rat. Human erythrocytes labelled with [Ga]oxine were shown to be viable up to 2 hours post-labelling, and washout of the radiolabel was minimal up to 1 hour post-labelling. Further optimization of the labeling method to translate for use in human cardiac and oncologic blood pool PET imaging studies, is underway.

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Development of 68Ga labeled human serum albumin for blood pool imaging: a comparison between two ligands

Cited by 9 publications

References 26 publications

Development of ^99mTc-Labeled Human Serum Albumin with Prolonged Circulation by Chelate-then-Click Approach: A Potential Blood Pool Imaging Agent

Development of ^99mTc-Labeled Human Serum Albumin with Prolonged Circulation by Chelate-then-Click Approach: A Potential Blood Pool Imaging Agent

Versatile and Finely Tuned Albumin Nanoplatform based on Click Chemistry

Automated synthesis of [⁶⁸Ga]oxine, improved preparation of⁶⁸Ga-labeled erythrocytes for blood-pool imaging, and preclinical evaluation in rodents

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Development of 68Ga labeled human serum albumin for blood pool imaging: a comparison between two ligands

Cited by 9 publications

References 26 publications

Development of 99mTc-Labeled Human Serum Albumin with Prolonged Circulation by Chelate-then-Click Approach: A Potential Blood Pool Imaging Agent

Development of 99mTc-Labeled Human Serum Albumin with Prolonged Circulation by Chelate-then-Click Approach: A Potential Blood Pool Imaging Agent

Versatile and Finely Tuned Albumin Nanoplatform based on Click Chemistry

Automated synthesis of [68Ga]oxine, improved preparation of68Ga-labeled erythrocytes for blood-pool imaging, and preclinical evaluation in rodents

Contact Info

Product

Resources

About

Development of ^99mTc-Labeled Human Serum Albumin with Prolonged Circulation by Chelate-then-Click Approach: A Potential Blood Pool Imaging Agent

Development of ^99mTc-Labeled Human Serum Albumin with Prolonged Circulation by Chelate-then-Click Approach: A Potential Blood Pool Imaging Agent

Automated synthesis of [⁶⁸Ga]oxine, improved preparation of⁶⁸Ga-labeled erythrocytes for blood-pool imaging, and preclinical evaluation in rodents