In vivo molecular malacological screening of specific uptake of commonly used radiopharmaceuticals in the leopard slug (Limax maximus) PET/SPECT imaging to determine effectiveness and human homology

Imagine the world of medical detectives trying to solve the mystery of how new medicines travel through the body. For decades, to see where a drug goes, scientists have had to use small mammals like mice and rats as their test subjects. It's a bit like using a complex, expensive, and ethically heavy machine to test a simple idea. But science is always looking for a lighter, friendlier way to do things. Enter the world of "molecular imaging," a high-tech way of taking pictures of the inside of a body using special glowing tracers. Think of these tracers as tiny, glowing fireflies injected into the bloodstream; as they travel, cameras can snap photos of exactly where they stop and stick, revealing which organs are hungry for the medicine and which are just letting it pass through. The big question scientists are asking right now is: Can we swap out the mice for something simpler, cheaper, and less controversial? Something that still has a body complex enough to tell us something useful, but doesn't require the same ethical heavy lifting?

This is where the story of the leopard slug comes in. The paper you are about to read explores a very curious idea: Could a garden slug, specifically the leopard slug (Limax maximus), be the new superstar of medical testing? These slugs are easy to keep, they breed like crazy, and they don't have the same "feelings" or nervous systems as mammals, making them a much more ethically friendly option. The researchers wanted to see if these squishy creatures could act as a stand-in for humans when testing eight different, very famous medical tracers used in hospitals today. They wanted to know: If we inject a human medicine into a slug, does it light up the same organs? Does it behave like it does in a human body, or does the slug just swallow it and forget it? It's a bit like testing a new key in a lock that looks nothing like a door; does it still turn, or does it just fall out?

The Great Slug Glow-Up

In this study, the scientists took eight different "glowing keys" (radiopharmaceuticals) that doctors use to scan human hearts, brains, bones, and tumors. They gently injected these glowing tracers into the foot of the leopard slug. Because slugs have an "open" circulatory system—imagine their blood (or hemolymph) flowing freely in a big pool rather than being trapped in tight pipes like in humans—the tracers spread through the slug's body very quickly. After waiting a couple of hours, they put the slugs into a giant, high-tech camera (a PET/SPECT scanner) to see where the glow ended up.

The results were a mix of "Whoa, that's exactly like humans!" and "Wait, that's totally weird."

The Heart and Kidney Connection
For several tracers, the slug's heart and kidney area lit up like a neon sign. This is actually great news because in humans, these organs are often the ones that filter out or process these medicines.

• One tracer called [123I]I-mIBG, which is used to look at heart nerves in people, showed a massive spike in the slug's heart/kidney area. The activity was 32.83 times higher than the background level. It was the only place this tracer really cared about, suggesting the slug's heart handles this chemical very similarly to a human heart.
• Another tracer, [18F]FDG (the one used to find cancer because it loves sugar), also lit up the heart area. The researchers even spotted two distinct bright spots that looked like the slug's heart chambers. This matched what we see in humans and mice, showing that slugs use sugar in their hearts just like we do.

The Brain and the "Ganglia"
The slug's brain is called a "ganglia." Usually, this part of the body is hard to see with these tracers. However, one specific tracer, [99mTc]Tc-sestamibi, made the slug's brain glow brightly. The activity ratio was 4.71, meaning the brain showed notable accumulation of this chemical, while the other seven tracers showed little to no uptake in this region. This is a unique finding that suggests the slug's brain might have a special way of grabbing this specific type of medicine.

The Stomach and Digestive Tract
The slug's stomach and digestive gland (a big organ that helps digest food) were also popular destinations.

• [68Ga]Ga-PSMA, a tracer used to find prostate cancer in humans, showed up strongly in the slug's stomach and digestive gland. The stomach had a ratio of 4.44, and the digestive gland had 2.32.
• [123I]I-ioflupane, which looks for dopamine (a brain chemical), also lit up the stomach and digestive gland with a ratio of 4.53.
  This suggests that in slugs, these organs might be doing the job of filtering or processing these chemicals, similar to how the liver and kidneys work in humans.

The Mystery of the Shell
Here is where things got really interesting and a little confusing. Slugs have an internal shell, a tiny plate inside their body.

• When the scientists used [99mTc]Tc-HDP, a tracer designed to stick to human bones, the slug's internal shell glowed incredibly bright. The activity was a staggering 28,700.68 times higher than the background! This suggests the tracer is sticking to the shell's minerals (which are made of calcite and aragonite, not human bone).
• However, when they used [18F] NaF, another tracer that usually sticks to bones, the shell stayed dark. It showed almost no uptake (a ratio of just 1.01).
  This is a huge difference. It tells us that while the slug's shell can grab some bone-hunting chemicals, it doesn't grab them all. It's like a lock that accepts one key but rejects another, showing that slug shells are chemically different from human bones.

What Didn't Work (or Wasn't Clear)
Not every tracer behaved perfectly. The tracer [68Ga]Ga-edotreotide, which targets specific receptors in human tumors, showed only a mild increase in the slug's heart and other organs. The researchers suggest this might be because slugs have a similar chemical cousin to the human receptor, but they aren't 100% sure which one it is yet. They also noted that the slug's nervous system didn't light up for PSMA, which contradicts what was seen in other related creatures, meaning there is still a lot to learn about how these chemicals interact with slug brains.

The Verdict

So, what does this all mean? The study suggests that the leopard slug is a promising, low-cost, and ethically friendly alternative for testing how medicines move through the body. For some tracers, the slug acts almost exactly like a human, lighting up the heart and digestive organs in the same way. For others, like the bone tracers, the slug behaves differently, which is actually useful information in itself—it tells scientists where the "human model" might break down.

The researchers are careful to say this is just the beginning. They haven't proved that slugs can replace mice for everything, but they have shown that slugs can be a great "first look" model. They can help scientists figure out if a new medicine is worth testing on more complex animals, or if it's just going to get stuck in a slug's shell. By using these garden creatures, science might be able to reduce the number of mice and rats used in research, making the path to new cures a bit kinder and a lot more efficient. The leopard slug, it turns out, might just be the unsung hero of the future of medical imaging.