What Is Nuclear Medicine? The Tracer Principle

In the early 1910s a young chemist named George de Hevesy was given a job he could not do. His task was to separate “radium D”, a radioactive substance, from the ordinary lead it was mixed with. He failed: radium D, we now know, is lead — a radioactive isotope of it — so no chemical method could ever pull the two apart.

By 1913 Hevesy had turned the failure around [1]. If radium D could not be separated from lead, then wherever lead went, radium D would go too. And because radium D announces itself with radiation, it could be used to follow lead through a chemical reaction — and, a decade later, through a living bean plant. A radioactive atom could act as a spy inside an ordinary molecule. That idea earned him the Nobel Prize in Chemistry for 1943 [2], and it is still the whole of nuclear medicine in one sentence.

The tracer principle in three steps

Every nuclear medicine procedure, from a routine bone scan to a cutting-edge cancer therapy, follows the same three steps.

1. Choose a molecule that goes somewhere interesting. It might mimic glucose, bind a receptor that cancer cells over-express, or be absorbed by the thyroid. The molecule’s chemistry and biology decide its destination.
2. Attach a radioactive atom. This atom — a radionuclide — is the messenger or the weapon. It is chosen so that it does not change where the molecule goes (in practice, designers work hard to make sure of this; we cover how in Part IV of this series).
3. Use the radiation. If the radionuclide emits photons that escape the body, a camera outside can record where the molecule went. If it emits particles that stop within a fraction of a millimetre or a few millimetres, it deposits its energy — and damages cells — right where the molecule went.

The amounts involved are astonishingly small. A typical FDG PET scan uses a few hundred megabecquerels of fluorine-18 — at 370 MBq, that is about a tenth of a nanogram of radioactive fluorine atoms. Even a full therapeutic dose of 7.4 GBq of lutetium-177 corresponds to only about two micrograms of the radionuclide itself (our calculation from the half-lives [4]). Quantities this small do not disturb the biology they are reporting on. That is what makes them tracers.

Function, not anatomy

Most of medical imaging shows structure. An X-ray or CT scan sends radiation through the body from a machine outside it and records how much each tissue absorbs, producing a picture of shapes and densities. MRI uses magnetic fields and radio waves, again mostly to show anatomy.

Nuclear medicine works the other way round. The source of radiation is inside the patient, attached to a molecule, so the image shows what tissues are doing: which ones are consuming glucose, which carry a particular receptor, where bone is being remodelled, how blood is flowing into the heart muscle.

The most widely used example is FDG, a glucose look-alike carrying fluorine-18. Cells take FDG up as if it were glucose and start to process it, but the first chemical step traps it inside the cell. Many cancers burn glucose avidly, so they light up on an FDG PET scan [5]. The same principle has limits — the brain, the heart and inflamed tissue are hungry for glucose too — which is one reason more specific tracers have been developed.

Function can change before structure does, or without it. A lymph node can look normal in size on CT yet contain cancer cells that a targeted PET scan picks up. That is why nuclear medicine is so often combined with CT or MRI in a single machine (PET/CT, SPECT/CT, PET/MR): one shows where things are, the other shows what they are doing.

Two halves: diagnosis and therapy

Nuclear medicine is far bigger than most people realise. The World Nuclear Association estimates over 50 million procedures a year worldwide: over 20 million in the United States and about 10 million in Europe, around 2 million of which are therapeutic [3]. Roughly 90% are diagnostic [3].

One radionuclide dominates the diagnostic side: technetium-99m (⁹⁹ᵐTc), used in about 80% of all procedures [3]. It is close to ideal for imaging. Its half-life of about six hours [4] is long enough to prepare a dose and complete a scan, but short enough that the radioactivity fades quickly afterwards. And it emits a single gamma photon of about 140 keV [4], energetic enough to escape the body but easy for a camera to stop and record. Heart perfusion scans, bone scans and thyroid scans are everyday ⁹⁹ᵐTc examinations. PET, the other major imaging technology, uses positron emitters such as fluorine-18 and gallium-68.

Therapy is the smaller half but the fastest-moving one. Its history begins on 31 March 1941, when Saul Hertz at Massachusetts General Hospital gave radioactive iodine to a patient with an overactive thyroid [6]. The thyroid concentrates iodine, so the radioiodine treated the gland from the inside. Radioiodine is still standard care for thyroid disease and thyroid cancer today.

The modern form of the same idea is radioligand therapy: a radionuclide attached to a molecule that seeks out cancer cells. Lutathera, for neuroendocrine tumours, was approved in the United States in 2018 [7]; Pluvicto, for prostate cancer, in 2022 [8]. Both carry lutetium-177, a beta emitter whose particles travel up to about 1.7 mm in tissue [9] — far enough to hit a cluster of cells around each bound molecule, short enough to spare most healthy tissue further away.

Whether a radionuclide is used for imaging or for therapy comes down to the kind of radiation it emits. Imaging needs photons that escape the body: gamma rays, or the pair of 511 keV photons produced when a positron meets an electron. Therapy needs particles that stay local and deposit their energy in a small volume: beta particles, alpha particles or Auger electrons. Part III of this series explains these in detail.

Theranostics: see it, then treat it

Some radionuclides do both. Iodine-131 emits beta particles, which treat, and gamma rays, which can be imaged [4]. Hertz’s radioiodine was therefore the first theranostic — a word that simply joins therapy and diagnostics.

Today theranostics usually means a pair: the same target is imaged with one radionuclide, then treated with another. Prostate cancer is the clearest example. Prostate cancer cells usually carry a protein called PSMA on their surface. A PSMA PET scan, for example with gallium-68, shows whether a patient’s tumours carry enough PSMA. If they do, the patient can be treated with Pluvicto, which carries lutetium-177 to the same protein. The drug’s label requires exactly this: patients are selected by a PSMA PET scan before treatment [8], as they were in the VISION trial that led to its approval [10].

Lutetium-177 also emits low-energy gamma rays [4], so after treatment a SPECT scan can show where the drug actually went — and how much radiation each tumour and organ received.

There is a subtlety worth flagging early. In the prostate example the “pair” is really two different molecules that bind the same protein, not one molecule carrying two different radionuclides. Whether that matters — and how designers build true matched pairs — is the subject of Part IV.

How much radiation is involved?

Nuclear medicine uses three different units, and mixing them up causes most of the confusion around radiation.

For a diagnostic scan the useful comparison is with natural background radiation. The FDG for a PET scan gives an effective dose of about 0.019 millisieverts per megabecquerel [12], so a 370 MBq injection gives about 7 mSv (the CT part of a PET/CT adds to this). Americans receive about 3 mSv a year from natural sources alone [13], so the tracer is roughly equivalent to two to three years of background radiation.

Therapy is deliberately different. The goal is a high absorbed dose — tens of grays — in the tumour, while keeping organs such as the kidneys, salivary glands and bone marrow below their limits. Getting that balance right is the science of dosimetry, the subject of article 8. Radioligand therapies do have side effects, such as dry mouth, tiredness and lower blood counts; we look at them, and at the field’s other hard problems, in article 20.

Why now?

Nuclear medicine is more than eighty years old, yet the past few years have been the busiest in its history.

These developments rest on the same century-old idea. What has changed is our ability to design molecules that find cancer cells precisely, to produce the right radionuclides at scale, and to prove in large trials that the result helps patients.

What comes next in this series

This is the first of 21 articles. Part II tells the history — from Becquerel’s photographic plates to total-body PET — because the story introduces almost every concept in a memorable order. Part III covers the physics and biology: how atoms decay, how different particles damage cells, where medical isotopes come from, how scanners work and how radiation dose is calculated. Part IV takes a radiopharmaceutical apart, piece by piece. Part V looks at what nuclear medicine does in the clinic today, and Part VI at the frontier: alpha emitters, new targets, the bottlenecks, and the rapid rise of nuclear medicine in China.

If you are new to the terminology, the companion piece Radionuclide or Radioisotope? explains two words you will see throughout.

References

1. Lindau Nobel Laureate Meetings. George de Hevesy — research profile (radium D as an indicator of lead). mediatheque.lindau-nobel.org/laureates/de-hevesy/research-profile
2. The Nobel Prize in Chemistry 1943: George de Hevesy, “for his work on the use of isotopes as tracers in the study of chemical processes”. NobelPrize.org. nobelprize.org/prizes/chemistry/1943/summary
3. World Nuclear Association. Radioisotopes in Medicine (updated 23 October 2026). world-nuclear.org
4. Laboratoire National Henri Becquerel (LNHB/CEA). Table de Radionucléides: decay data for ⁹⁹ᵐTc, ¹⁸F, ¹³¹I and ¹⁷⁷Lu. Masses calculated by XNucMed from the half-lives.
5. Fowler JS. ¹⁸F-FDG radiosynthesis: a landmark in the history of PET. J Nucl Med. 2020;61(Suppl 2):105S–109S. doi:10.2967/jnumed.120.250191
6. Fahey FH, Grant FD, Thrall JH. Saul Hertz, MD, and the birth of radionuclide therapy. EJNMMI Phys. 2017;4:15. doi:10.1186/s40658-017-0182-7
7. FDA approves Lutathera for gastroenteropancreatic neuroendocrine tumors (approval of 26 January 2018). Cancer Network, January 2018. cancernetwork.com
8. US Food and Drug Administration. PLUVICTO (lutetium Lu 177 vipivotide tetraxetan) prescribing information. accessdata.fda.gov
9. Stokke C, Kvassheim M, Blakkisrud J. Radionuclides for targeted therapy: physical properties. Molecules. 2022;27:5429. doi:10.3390/molecules27175429
10. Sartor O, de Bono J, Chi KN, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385:1091–1103. doi:10.1056/NEJMoa2107322
11. US Nuclear Regulatory Commission. Release of patients administered radioactive material (10 CFR 35.75 guidance). nrc.gov/docs/ML1716/ML17166A200.pdf
12. International Commission on Radiological Protection. Radiation dose to patients from radiopharmaceuticals: a compendium of current information related to frequently used substances. ICRP Publication 128. Ann ICRP. 2015;44(2S).
13. National Council on Radiation Protection and Measurements. Ionizing radiation exposure of the population of the United States. NCRP Report No. 160. 2009.
14. Novartis. FDA approves Pluvicto for PSMA-positive metastatic hormone-sensitive prostate cancer. Media release, 31 July 2026. novartis.com
15. Bristol Myers Squibb completes acquisition of RayzeBio. BioSpace, 26 February 2024. biospace.com
16. Bristol Myers Squibb. Positive topline results from the interim analysis of Phase 3 ACTION-1 for RYZ101. Press release, 12 October 2026. news.bms.com