Radiopharmaceuticals: Individualized diagnostics and therapy

Malignant tumors can be fought with X-rays – usually with radiation therapy from outside the body. Nuclear medicine physicians can also accomplish this inside the body with radioactive materials, called radiopharmaceuticals. They also offer big benefits for clinical diagnostics as long as a specific target can be assigned to them.


Photo: PET-Scanner

Radiopharmaceuticals are drugs containing radionuclides whose radiation is used in diagnostic and therapy; ©

The field of imaging has changed dramatically over the past few years and molecular imaging has increasingly become more prominent. Nuclear medicine makes molecular processes in the body visible to detect disease processes early and enable a targeted treatment. Examination techniques such as positron emission tomography (PET) or single-photon emission computer tomography (SPECT) cover this area. These methods are also able to illustrate tumor metabolism, that being a tumor’s response to a specific treatment, much sooner than an MRI or CT.

Both of these nuclear medicine imaging techniques focus on showing the function of individual organs by illustrating their metabolism. To do this, so-called radiopharmaceuticals that bind to specific antibodies, protein compounds, or sugar molecules are being introduced into the body.

"Radiopharmaceuticals have two components," explains Professor Torsten Kuwert, Director of the Erlangen University Hospital Department of Nuclear Medicine. "The first one is a radioactive isotope and the other another molecule that is attached to the radioactive isotope. It connects to target structures that are expressed in tumors, for example."

Photo: PET scan before therapy

PET/CT examination with the radiopharmaceutical Ga-68 DOTATOC of a neuroendocrine tumor before the begin of therapy; © Prof. Torsten Kuwert/UKE

A typical example of a radiopharmaceutical for diagnostic use is fluorine-18-deoxyglucose. Fluorine-18 is a radioactive fluorine isotope that decays by positron emission. This irradiation can be detected by positron emission tomography and its distribution in the tissue illustrated. The second molecule part – deoxyglucose – is sugar. The radiopharmaceutical is absorbed by the cells by this sugar content which exhibits an elevated glucose concentration. Certain types of cancers have an increased glucose metabolism. Conglomerations of malignant tumors can be detected with this.

Making malignant or healthy tissue visible

Generally, both malignant and healthy tissue can be detected with radiopharmaceuticals. Although there are radioactive materials that make healthy tissue visible – for instance, if you want to illustrate the excretory function of the liver or the hormone synthesis in the thyroid gland - yet their primary purpose is not to make healthy tissue and the body structure visible.

There is also a continuum between malignant and healthy tissue: when you want to diagnose Alzheimer’s disease with fluorine-18-deoxyglucose using positron emission tomography, areas of the brain that don’t function as well and exhibit less concentrations are made visible. Unlike when you want to illustrate a tumor, which generates a higher signal due to an increased concentration of radiopharmaceuticals.
Photo: PET scan after therapy

Partial treatment success of a neuroendocrine tumor through somatostatin radioreceptor therapy; © Prof. Torsten Kuwert/UKE

All-rounder radiopharmaceutical: from diagnosis to treatment

Of course, there are also therapeutic radiopharmaceuticals. "They emit short-range particulate radiation in radioactive decay, for instance, electrons. Whereas, as little tissue as possible is being damaged during a diagnostic evaluation, during treatment, a specific tissue type is being attacked and destroyed," Kuwert explains.

This is why personalized approaches play an increasing role in radiopharmaceutical development. "Certain types of cancer cultivate specific target molecules but not in all patients. Not every pharmaceutical that proves effective in a clinical trial works the same way in all patients. There are different ways to use radiopharmaceuticals to control and predict the response. Of course, the most elegant case is to directly utilize the target structure that is also activated during the treatment for diagnostic purposes with a radiopharmaceutical. After all, if a tumor doesn’t have this target structure, the treatment is not successful. The development in this field is presently very intense and is partially already being implemented in practice."

Effectiveness confirmed for prostate cancer

Just recently, there has been a breakthrough in the diagnosis and treatment of prostate cancers. The German Cancer Research Center in Heidelberg developed a radiopharmaceutical that facilitates both the diagnosis of tumors and their metastasis in the body and treatment.

Kuwert confirms: "This is a beautiful example of personalized medicine. By using the diagnostic radiopharmaceutical, you can show that a specific prostate cancer exhibits the prostate-specific membrane antigen (PSMA) in high density; you are subsequently able to bind the same molecular structure to a therapeutic radionuclide such as Lutetium-177 and treat the tumor."

The ever-widening spectrum of effective types of radiopharmaceutical therapies that are actuated via the same molecule offers great potential and will, therefore, continue to keep research busy in the future.
Photo: Melanie Günther; Copyright: B. Frommann

©B. Frommann

The article was conducted by Melanie Günther and translated from German by Elena O'Meara.