radiotracer

Days 23-26: July 5-8: Nuclear Medicine Week

Nuclear Medicine Week. 75% of the students in this program will shudder at the very mention of this name. But, because I cater to those who want to learn and share in my experiences, I will recount my survival of Medicine Week for those readers who might be interested in the material. Who I commend for their bravery and dedication to such a ridiculous (but very important) science.

Tuesday: Dr. Cathy Cutler from Washington University in Missouri and Dr. Henry Van Brocklin from University of California-San Francisco were our guest lecturers for the week. Dr. Cutler also works at the University of Missouri Research Reactor (MURR.) I had the hardest time staying awake for all 6 hours of lecture this day. But I took some notes on some interesting things so bear with me:

  • Radiotracers are very small amounts of a radioactive isotope that are injected into the body that participate in biological processes but do not perturb the processes. It can be used either for treatment or diagnosis of diseases. 
  • The Magic Bullet was Paul Ehrlich’s idea to use a drug that would seek out and attack the ‘parasitic invader’ but not harm the host. This resulted in the cure for syphilis in 1909. He also attached toxins to antibodies so that the body could naturally transport the drug to the diseased site. This paved the way for the development of immunotoxins.
  • Technetium-99m is a very important isotope that is used extensively in radiopharmacy. We’ll come back to all the cool things it does.
  • Imaging! I’m sure most of you have heard of one of the following: MRI (Magnetic Resonance Imaging), SPECT (Single-Photon Emission Computed Tomography), or PET (Positron-Emission Tomography) scans. I’ll go into detail about them later.
  • Radiolabeled Probes/Drugs: there were a couple stories in here about how iodine-123 is used for treatment of the thyroid (maybe for cancer?? I don’t know, my notes started to suck at this point) and strontium-90 is used to treat bone cancer. Also, it is difficult to get the isotope to go exactly where you want it to in the body, so that is a current challenge. Other challenges to consider when using radioisotopes in medicine are production capacity (can we make enough of it for efficient use?) and the economy (can we afford to regularly make the drug with this isotope?) Something to keep in mind is that every radioisotope used in medicine has to have a fairly short half life so that it decays away quickly and the patient doesn’t receive an excess dose of radiation. That means the production of the drug needs to be fast, and the process of administration to the patient needs to be fast. 
  • George de Hevesy did research with radioactive isotopes of lead-210 (which he thought were forms of radium, called “radium-D”) in Ernest Rutherford’s lab in his earlier career, won the 1943 Nobel Prize in chemistry for his studies of radiotracers in plants, animals, and humans, developed the technique of neutron activation analysis (NAA - you’ll hear about this technique later) and discovered element # 72, Hafnium. He was an accomplished man, but throughout the course of Medicine Week we heard this famous landlady story about his first radiotracer 'investigation’ a billion times: While at boarding school in Manchester, England, he suspected that the landlady was recycling their food scraps from each meal after he began having chronic upset stomach. To test his hypothesis, he placed trace amounts of radioactive material in the Sunday meal, then tested the meal served a few days later, confirming the presence of radioactivity in the food and confronting a bewildered landlady. Cheeky Bastard.

Wednesday: I came to class prepared with an energy drink the size of my quad that day. I definitely enjoyed today’s lecture the best (maybe because I was awake for all of it??) Dr. Cutler talked about radionuclide generators because we did a lab that afternoon using one. Basically a generator is a device that produces a useful short-lived supply of a medical radionuclide (called the “daughter” in nuke chem) from a non-medical long-lived radionuclide (called the “parent.”) [Note: the reaction is the parent with the long half-life decays into the daughter with the short half-life.] Here’s a summary of the lab we did, which includes the concepts that complemented it from lecture:

  1. Prepared Technetium-99m PnAO (the “m” means “meta-stable,” so a very short half-life) by directly combining 99mTcO4-, PnAO, Sn2+ and NaHCO3.
  2. Prepared it again using a Glucoscan kit as an exchange ligand. The kit contains glucoheptonate, Sn2+ and some other stabilizers.
  3. Executed paper chromatography using the Technetium-99m PnAO produced using both the above methods with ether, acetone, and saline as the chromatography solvents.
  4. Executed a solvent extraction on both types of Technetium-99m PnAO solutions, separating the 99mTcPnAO from the pertechnetate anion and the 99mTc-GH in ether and saline. The former compound partitioned into the organic ether layer, while the latter two sank into the aqueous saline layer.
  5. Both the Chromatography and Solvent Extraction methods were used to illustrate the concept of Quality Control. QC just checks on the purity of the compounds used in the generator, to make sure you are synthesizing exactly what you need and the amount of that product you need without the presence of by-products (radiochemical purity) or other unwanted isotopes (radionuclidic purity.)

I’m convinced that the write-up instructions for this lab were sent to us directly from Hell. I even received an email from Dr. Van Brocklin asking if I sent him the entire report or if the last few pages got lost in cyberspace… I had to assure him that what I sent him was my report in its entirety :P But in happier news, all the suffering I endured last Fall semester in Biochemistry I paid off… I understood quite a bit of the chemistry between the radionuclides and the body! Yay for retention! Also, for all you biochem kids out there, when Dr. Cutler starting talking about 'current Good Manufacturing Practice,’ or 'cGMP,’ all I could think about was cyclic guanosine monophosphate! Hahaha

Thursday: Dr. Van Brocklin lectured for a RIDICULOUS AMOUNT OF TIME about PET scans. No one should know that much about PET, let alone choose to teach it to a group of nuclear chemistry students who would rather play with accelerator beams and fission reactions than even utter the words “molecular imaging.” However, we sally forth. Dr. Cutler talked about MURR and the research she does over there with medical radioisotope production. The MURR, as the name suggests, is home to a nuclear reactor that uses a flux of neutrons generated in the cyclotron to produce molybdenum-99 (which decays to the famous technetium-99 isotope) as well as many other medical radionuclides.

Friday: **TO BE CONTINUED**

The art of...

Nuclear medicine is a branch of medical imaging that uses small amounts of radioactive material to diagnose and determine the severity of or treat a variety of diseases, including many types of cancers, heart disease, gastrointestinal, endocrine, neurological disorders and other abnormalities within the body. Because nuclear medicine procedures are able to pinpoint molecular activity within the body, they offer the potential to identify disease in its earliest stages as well as a patient’s immediate response to therapeutic interventions.

Diagnosis

Nuclear medicine imaging procedures are noninvasive and, with the exception of intravenous injections, are usually painless medical tests that help physicians diagnose and evaluate medical conditions. These imaging scans use radioactive materials called radiopharmaceuticals or radiotracers.

Depending on the type of nuclear medicine exam, the radiotracer is either injected into the body, swallowed or inhaled as a gas and eventually accumulates in the organ or area of the body being examined. Radioactive emissions from the radiotracer are detected by a special camera or imaging device that produces pictures and provides molecular information.

In many centers, nuclear medicine images can be superimposed with computed tomography (CT) or magnetic resonance imaging (MRI) to produce special views, a practice known as image fusion or co-registration. These views allow the information from two different exams to be correlated and interpreted on one image, leading to more precise information and accurate diagnoses. In addition, manufacturers are now making single photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT) units that are able to perform both imaging exams at the same time. An emerging imaging technology, but not readily available at this time is PET/MRI.

Therapy

Nuclear medicine also offers therapeutic procedures, such as radioactive iodine (I-131) therapy that use small amounts of radioactivematerial to treat cancer and other medical conditions affecting the thyroid gland, as well as treatments for other cancers and medical conditions.

Non-Hodgkin’s lymphoma patients who do not respond to chemotherapy may undergo radioimmunotherapy (RIT).

Radioimmunotherapy (RIT) is a personalized cancer treatment that combines radiation therapy with the targeting ability ofimmunotherapy, a treatment that mimics cellular activity in the body’s immune system.