Tag Archives: PET

H2hox and Gallium: A Dynamic Duo in Medical Imaging

Posted on April 5, 2020 by | Leave a comment

Not every molecule gets to find their best “partner” in life. Luckily in 2019, Dr. Chris Orvig and his team at the University of British Columbia constructed a partner molecule for Gallium to work with in medical imaging. They also determined that their creation has superior stability and binding ability compared to similar molecules currently being used.

THE NEW MOLECULE IN TOWN

The partner molecule is a chelating ligand known as H2hox. Let’s break down its name piece-by-piece to get a better understanding of what it does.

A ligand is a molecule that binds onto a metal ion such as iron (Fe3+) or copper (Cu2+). In the case of H2hox, the metal ion is Gallium (Ga3+ ).

The word chelating comes from the latin root word chela, which means claw. This is because chelating ligands have multiple points of attachment to a metal ion, similar to a crab’s claw, making them significantly stronger binders to metal ions.

Image sources (left to right): Research Gate, Wang et al..

THE DUO GETS TO WORK

H2hox is used in a form of medical imaging known as positron-emission tomography (PET). PET imaging is used to diagnose health issues related to the processes occurring inside our cells, such as cancer.

The main function of H2hox in PET imaging is to bind to radioactive Gallium ions, which aids in producing an image of a desired area or tissue inside the body.

To test how well H2hox worked together with its partner, Gallium, the researchers conducted a PET scan in mice. The group witnessed high stability of the dynamic duo within mice, and they observed that it was rapidly excreted from the mice, which is important for a decrease in side effects.

Furthermore, the ligand has a strong affinity to Gallium, such that only low amounts of ligand are needed to significantly bind to Gallium ions in just five minutes! As a result of the molecule’s advanced properties, H2hox surpasses any ligand currently used as a Gallium’s partner.

ALL IT TAKES IS 1 STEP

In the lab, H2hox is synthesized (made) in only one reaction and is easy to purify, unlike similar ligands which are synthesized over multiple labor- and resource- intensive steps. As a bonus, the chemicals used to make it are inexpensive and readily available.

To put this into perspective, it’s like baking a box cake versus baking a cake from scratch. The former is quite easy to do, while the latter is a lot harder and is more labour-intensive. Ease of manufacturing is a key feature because it determines the commercial success of the product.

THE FUTURE IS PROMISING

The combination of unprecedented properties and easy synthesis makes H2hox a launching-off point for the development of even better chelating ligands to improve the future of PET imaging. With H2hox being such an advantageous molecule for Gallium PET imaging, we cannot wait to see what else this dynamic duo has to offer the world.

Literature cited:

  1. Wang, X.; Jaraquemada-Pelaez, M. d. G.; Cao, Y.; Pan, J.; Lin, K.-S.; Patrick, B.O., Orvig, C. H2hox: Dual-Channel Oxine-Derived Acyclic Chelating Ligand for 68Ga Radiopharmaceuticals. J. Am. Chem. Soc. 2019, 58, 2275-2285

 

-Group 6 (Mark, Akash, Athena, Charles)

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Posted in Biological Chemistry, Chemistry News, Inorganic Chemistry, Uncategorized

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A New and Advantageous Molecule for Diagnostic Nuclear Medicine

Posted on March 29, 2020 by | Leave a comment

You may be aware of the role physicists and doctors play in diagnostic nuclear medicine; however you may not know that chemists also play a significant role in this area of science! In 2019, Dr. Chris Orvig and his team at the University of British Columbia constructed an advantageous molecule for use in medical imaging whose purpose is to bind to radioactive Gallium (Ga) ions. They also determined that their molecule has superior properties to similar molecules currently being used.

WHAT IS IT?

The molecule that was created by Dr. Orvig’s team is simply known as H2Hox , a chelating ligand. Let’s break its name down piece-by-piece to get a better understanding of what it does.

A ligand is a type of molecule that can bind onto a metal ion, like iron (Fe3+) or copper (Cu2+). In the case of H2hox, the metal ion is Gallium (Ga3+) because it is widely used in medical imaging. The word chelating comes from the latin root word chela, which means claw. This is because chelating ligands have multiple points of attachment to a metal ion, similar to a crab’s claw, making them significantly stronger binders to metal ions.

Image sources (left to right): Research Gate, Wang et al..

HOW IS IT MADE?

H2Hox is easy to synthesize, avoiding a number of potentially challenging synthetic pathways typically associated with Ga chelating species. The initial starting materials were inexpensive and readily available. To put this into perspective, it’s like baking a box cake versus baking a cake from scratch. The former is simple and quite easy to do, while the latter is a lot harder and is a lot more intensive. Ease of synthesis is an important feature as it can affect the commercial applicability of the molecule.

WHAT DOES IT DO?

H2Hox is used in a form of medical imaging known as positron-emission tomography (PET). PET imaging is primarily used to diagnose health issues related to biochemical processes occurring inside our cells, such as cancer. The main function of H2Hox in PET imaging is to bind to the radioactive Gallium ion, which aids in producing an image of a desired area or tissue inside the body.

To test how well H2Hox worked, the researchers conducted a PET scan in mice. The group witnessed high stability of the combined ligand and ion in mice, and more importantly, they observed that it was rapidly excreted from the mice. Furthermore, the ligand has a strong affinity to Gallium, exhibiting significant radiolabeling capabilities (binding to Ga3+) in only five minutes with low amounts of ligand under room temperature. As a result of the molecule’s advanced properties, H2Hox surpasses any ligand currently used as a Gallium chelator.

THE FUTURE IS PROMISING

The combination of superior properties and easy synthesis makes H2Hox an effective and convenient molecule for Gallium PET imaging. H2Hox acts as a launching-off point for the development of even better chelating ligands to improve the quality and ease of PET imaging.

Literature cited:

1. Wang, X.; Jaraquemada-Pelaez, M. d. G.; Cao, Y.; Pan, J.; Lin, K.-S.; Patrick, B.O., Orvig, C. H2hox: Dual-Channel Oxine-Derived Acyclic Chelating Ligand for 68Ga Radiopharmaceuticals. J. Am. Chem. Soc. 2019, 58, 2275-2285

 

-Group 6 (Mark, Akash, Athena, Charles)

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68Ga and H2hox: A Dynamic Duo

Posted on March 23, 2020 by | Leave a comment

Not every molecule gets to find their best partner in life. Luckily, in 2019, Orvig and his team at the University of British Columbia made a perfect partner for Gallium-68 (68Ga) to improve the results of medical imaging.

Medical imaging encompasses tests such as X-rays and ultrasound, and these tests allow doctors to look inside of our bodies to determine if there are any problems, or to monitor any changes post-surgery. Therefore, it is important that the science and technique behind the imaging is advanced, and that the results can be obtained quickly and accurately.

WHAT IS 68Ga?

68Ga, is an imaging tracer used in positron emission tomography (PET) scan, which is a type of imaging test. With a relatively short half-life, 68Ga wants to perform to the best of its ability during the test, and it yearns for an efficient partner to help show activity within the tissues. However, current partners present limitations in terms of synthesis and performance.

H2hox: IS IT THE ONE? 

Therefore, researchers created a molecule named H2hox. Unlike previous candidates for 68Ga, H2hox was easily synthesized within two steps. The team saw how strongly attracted H2hox was to 68Ga, and that only mild conditions and low concentrations of H2hox were needed for the two to bind together.

Figure 1. The chemical structure of H2hox. Adapted from Wang et al. (2019).

Once bound, the team found that a highly stable metal complex, [68Ga(hox)]+, was formed within the pH range of 1 to 11. Furthermore, this complex only existed as a single species, and did not require further purification. Because these combined characteristics were impossible to achieve with previous partners, the researchers thought that H2hox could be the one for 68Ga.

TESTING THEIR TEAMWORK

To test how well this complex worked in real life, the researchers conducted a PET/computed tomography (CT) scan in mice. The group witnessed high stability of the metal complex in mice, and more importantly, they observed that the metal complex was rapidly excreted from the mice. 

Furthermore, because the fluorescence intensity of H2hox increased upon complexing with 68Ga, the team thought that the complex could be used to analyze intracellular distribution and stability studies.

Figure 2. The fluorescence intensity of H2hox increased by fourfold when it was part of the [Ga(hox)]+complex. Adapted from Wang et al. (2019).

THE FUTURE IS PROMISING

Since the researchers also observed a fast heart uptake of the complex in mice, they suggested that H2hox could form the basis for tracers in heart imaging. Additionally, the team proposed that this complex could benefit fluorescence-directed surgery.

With this many unprecedented advantages, we cannot wait to see what else this dynamic duo has to offer the world.

 

Story source

Wang, X.; Jaraquemada-Pelaez, M. d. G.; Cao, Y.; Pan, J.; Lin, K.-S.; Patrick, B.O., Orvig, C. H2hox: Dual-Channel Oxine-Derived Acyclic Chelating Ligand for 68Ga Radiopharmaceuticals. J. Am. Chem. Soc. 2019, 58, 2275-2285

-Athena Wang

 

 

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Orvig Group at UBC Creates Novel Molecule for Diagnostic Nuclear Medicine

Posted on March 22, 2020 by | Leave a comment

You may be aware of the role physicists and doctors play in diagnostic nuclear medicine, however you may not know that chemists also play a significant role in this area of science!

In 2019, Chris Orvig of the Medicinal Inorganic Chemistry Group at the University of British Columbia (UBC) created a new organic molecule for medical imaging. They also determined that their novel organic molecule has superior properties to similar molecules currently being used.

The molecule created by the inorganic chemistry group at UBC is simply known as H2hox, a hexadentate chelating ligand. What exactly does that mean? Let’s break it down piece-by-piece.

A ligand is a type of molecule that can bind onto a metal ion, like sodium (Na+) or calcium (Ca2+). In the case of H2hox, the metal ion it’s binding to is Gallium (Ga3+) because it is used in medical imaging.

The word chelating comes from the latin root word chela, which means claw. This is because chelating ligands have multiple points of attachment to a metal ion, similar to a crab’s claw, making them significantly stronger binders to metal ions.

The word hexadentate comes from the latin root words hexa, which means six and dent, which means tooth. So a hexadentate chelating ligand has six attachment points, or teeth, that can grab onto a desired metal ion.

Image sources (left to right): Research Gate, Orvig et al..

 

So why is H2hox used in medical imaging?

Molecules such as H2hox are used in a form of medical imaging known as Positron-emission tomography (PET). John Hopkins Medicine defines PET imaging as “using a scanning device (a machine with a large hole at its center) to detect photons (subatomic particles) emitted by a radionuclide in the organ or tissue being examined”.

PET imaging is primarily used to diagnose health issues related to biochemical processes occurring inside our cells, such as cancer. The radionuclide, or radioactive atom, of choice for H2hox is Gallium ions. Since ions alone cannot be used in imaging, due to their poor mobility through our cells and tissues, they are packaged together with small organic molecules, such as H2hox, before injection into human tissue.

So what makes H2hox better than the current available options?

H2hox is an advantageous ligand for Gallium PET medical imaging because…

  • It can be easily synthesized (made) through only 1 reaction step.
  • It has a strong affinity to Gallium, exhibiting significant radiolabeling (binding to Ga3+) in only 5 minutes with low amounts of ligand and under mild conditions (room temperature)
  • The combined ligand and ion have excellent stability in vitro (inside cells) and in vivo (inside a beaker).

These combined properties make H2hox an effective and convenient molecule for Gallium PET imaging. Furthermore, Orvig’s research will act as a launching-off point for the development of even better ligands to improve the quality and ease of PET imaging and diagnosis.

I hope this news article educated you about medicinal inorganic chemistry through describing its role in medical imaging.

 

Literature cited:

Wang, X.; De Guadalupe Jaraquemada-Peláez, M.; Cao, Y.; Pan, J.; Lin, K. S.;                       Patrick, B. O.; Orvig, C. H2hox: Dual-Channel Oxine-Derived Acyclic                       Chelating Ligand for 68Ga Radiopharmaceuticals. Inorg. Chem.                                 [Online] 2019, 58, 2275-2285.                                                                                          https://pubs.acs.org/doi/10.1021/acs.inorgchem.8b01208 (accessed                      March 22, 2020).

 

-Mark Rubinchik

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