Our Science


The chelating agent 3,4,3-LI(1,2-HOPO) has been specifically optimized for the selective binding of heavy metals, and it promotes their rapid removal from the body. Unlike other chelating agents, it does so without depleting the body of essential mineral elements such as zinc and calcium. These properties are optimal for multiple clinical indications across several sectors, including pediatric and maternal health, environmental contamination, radiology and MRI contrast agents, defense and disaster preparedness, and nuclear energy research, waste treatment, and power plant operations.

Childhood Lead Poisoning

The consequences of lead (Pb) exposure during gestation and early childhood are both devastating and lifelong. Even low level exposure causes developmental disabilities such as hyperactivity, lower IQ, and attention deficits, as well as increased risk of kidney and cardiovascular disease later in life. Young children are particularly vulnerable to Pb exposure, as their growing bodies retain almost 500% more ingested Pb than adults. During pregnancy, Pb that has accumulated in the mother’s body can also be passed on to the developing child, placing them at risk and disadvantage even before birth. The available data show that the harm caused by Pb poisoning, particularly the neurological effects, cannot be undone. Thus, the only ways to minimize this lifelong damage are to remove Pb from a child’s body as quickly as possible, or more ideally to prevent its accumulation in the first place.

The societal and economic impact of Pb poisoning cannot be overstated. Exposed children are less likely to graduate high school and succeed by any available metric, and have a higher likelihood of juvenile delinquency, incarceration, and premature death. In the United States alone, the total economic cost of Pb poisoning is estimated at around $84 billion per year. Lower-income and minority communities make up the majority of the most severely affected areas, and the transgenerational impact of Pb poisoning only serves to further existing disparities in achievement, opportunities, and healthcare.

There is currently no treatment available for the overwhelming majority of children exposed to Pb. HOPO Therapeutics is developing its oral chelating agent as a best-in-class solution to this unmet need, and is committed to our vision of a world in which Pb poisoning is a treatable and passing diagnosis, rather than a life sentence for lower achievement and poorer health.

Gadolinium From MRI Contrast Agents

There are over 15 million magnetic resonance imaging (MRI) procedures performed in the United States each year that utilize an injected gadolinium-based contrast agent, or GBCA. The release of the toxic heavy metal gadolinium from these GBCAs results in gadolinium deposition throughout the body, and can lead to serious health complications. Currently there is no way to prevent or treat gadolinium deposition, and the diagnostic benefits of the contrast MRI are generally accepted to outweigh the risks.

In preclinical studies, 3,4,3-LI(1,2-HOPO) enabled the effective prevention of gadolinium deposition . Our oral formulation enables the course of treatment we believe will be the most effective at preventing gadolinium deposition: a regimen of pills taken in the days following contrast MRI to ensure that gadolinium released into the body from the GBCA compound will be chelated and excreted from the body, instead of depositing in the kidneys, brain, and bones.

We are evaluating the efficacy of 3,4,3-LI(1,2-HOPO) for removal of pre-existing, deposited gadolinium from patients who have already received GBCAs. The design of an effective dosing strategy requires a detailed knowledge of the compound’s pharmacokinetics in humans - information we anticipate will be available following our first-in-human clinical trial.

Finally, The American College of Radiology advises against the use of GBCAs for patients with impaired kidney function due to the risk of nephrogenic systemic fibrosis (NSF), making those individuals ineligible for MRI or MR angiography (MRA) with gadolinium-based contrast. Instead, patients with kidney disease often undergo alternative imaging procedures using ionizing radiation, such as CT or PET. GBCAs are normally cleared from the body through the kidneys, however the primary excretion route of 3,4,3-LI(1,2-HOPO) is via the liver. Using the compound to reduce the strain on the kidneys associated with clearing a large dose of GBCA could enable patients with kidney disease to undergo contrast MRI and MRA procedures, giving physicians ideal diagnostic information, and avoiding unnecessary exposure to radiation.

Radiological Disaster Preparedness

The oral formulation of 3,4,3-LI(1,2-HOPO) has been designed to provide a safe, easily distributed, effective treatment in a large-scale radiological incident. Additionally, the excellent prophylactic efficacy observed in preclinical studies suggests that 3,4,3-LI(1,2-HOPO) can provide an effective means to protect first responders, nuclear workers, or other individuals entering a radiological contamination zone. Inspired by the COVID-19 pandemic, the overhauling of the US Strategic National Stockpile will likely look to include next-generation treatments for a radiological or nuclear disaster scenario. HOPO Therapeutics is positioned to provide a best-in-class, uniquely orally-available treatment to both the US and foreign governments seeking to improve their strategic stockpile supplies. Read more

Accidental Exposure in Nuclear Workers

Despite rigorous safety protocols, people who handle radioactive material are sometimes inadvertently exposed to elements such as uranium, plutonium, americium, and other actinides. With an accelerated schedule of decommissioning of nuclear plants in France and other countries, as well as increased US production of plutonium-238 for space applications , there is a growing workforce of nuclear workers who are currently without a safe, reliable treatment option in the event of an accidental exposure.

Development and Properties

The development of HOPO Therapeutics’ flagship active pharmaceutical ingredient, 3,4,3-LI(1,2-HOPO), began with the aim of creating a pill that could be used to protect and treat people in a nuclear disaster scenario . After extensive investigation and pre-clinical evaluation, 3,4,3-LI(1,2-HOPO) emerged as a promising candidate capable of binding to, or chelating, heavy metals and removing them from the body. It has several properties that make it exceptionally suited to serve as a chelating agent for heavy metal toxicity.


The therapeutic interventions that are currently available for the treatment of heavy metal contamination, including EDTA and DTPA, will deplete the body’s supply of metal ions that are essential for the body’s function, such as iron, zinc, and calcium. Due to its size and molecular shape, the 3,4,3-LI(1,2-HOPO) chelates the f-block elements of the periodic table, including gadolinium, but does not chelate any essential ions. Read more

Oral Availability

The most convenient drug delivery route is an oral medication. This allows for easy self-administration, and is ideal for rapid distribution and treatment for a large population. In pre-clinical studies, 3,4,3-LI(1,2-HOPO) shows good oral availability, and it maintains efficacy when formulated as an oral capsule. Read more

Prophylactic and Delayed Efficacy

3,4,3-LI(1,2-HOPO) effectively removes heavy metals from the body when used either as a prophylaxis or when administered days or weeks following contamination. It can be used to provide protection prior to exposure to heavy metals, e.g. to protect first responders in a nuclear disaster scenario, as well as to treat patients that have already been contaminated. Read more

Rapid Clearance

Heavy metals are excreted quickly once bound by 3,4,3-LI(1,2-HOPO). This ensures that heavy metals spend a minimal amount of time in the body.

Related Publications

Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials
Structural and spectroscopic characterization of an einsteinium complex
Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents
Biodistribution of the Multidentate Hydroxypyridinonate Ligand [ 14 C]-3,4,3-LI(1,2-HOPO), a Potent Actinide Decorporation Agent
In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)