First, let’s review some basic concepts…
Theranostics is an approach that combines diagnosis and treatment by targeting the same receptors on tumor cells to detect them (diagnosis) or destroy them (therapy).
Theranostics = Therapeutics + diagnostics
With NET, the diagnostic phase of theranostics is typically performed with the Ga-68 dotatate scan (NETSPOT®) or Cu-64 dotatate scan (Detectnet™). This means that the dotatate scan is done and must show uptake, and indicate the presence of somatostatin receptors on the tumors, in order for a patient to be a candidate for PRRT treatment. [Note: Ga-68 DOTATOC is also FDA-approved for imaging.]
The therapeutic phase is PRRT.
PRRT = Peptide Receptor Radionuclide Therapy
PRRT is a targeted therapy where radiation is delivered to the tumor cells. Currently, the only FDA-approved PRRT therapy for NET in the United States is Lu-177 dotatate (Lutathera®). For more on the basics of PRRT, read the LACNETS blog post, These Four Letters: PRRT Part 1.
Note: Radioisotopes such as Ga-68 and Lu-177 are used not only for NET but also for other types of cancer. In this article, we address their use for NET.
Beta vs. Alpha
Beta and alpha particles are forms of radiation currently being used to treat NET in the form of PRRT. For more on radiation basics, read the United States Nuclear Regulatory Commission’s Radiation Basics.
Lu-177 dotatate or (Lutathera®) is a type of beta PRRT.
Although Lutathera® is currently the only FDA-approved PRRT, the other types of PRRT, notably alpha PRRT, are under investigation. There are two alpha isotopes available through clinical trials:
Actinium 225 or Ac-225 – The study is called “ACTION-1,” a phase 3 study sponsored by RayzeBio. For more information on eligibility criteria, trial locations, study details, etc., view this trial on ClinicalTrials.gov (NCT05477576).
Lead 212 or Pb-212 – The drug name is “AlphaMedix,” available through a clinical trial sponsored by Radiomedix and Orano Med. For more information on eligibility criteria, trial locations, study details, etc., view this trial on ClinicalTrials.gov (NCT05153772).
*Lu177 DOTATATE is the only FDA-approved treatment.
**In the USA, available only in the clinical trial as of April 2023
Currently, there are different types of PRRT trials:
PRRT naïve: Someone who has not had PRRT before
Someone who has had PRRT before
PRRT combination therapy: There are studies comparing Lu177 in combination with another drug, often used as a radiosensitizer, to enhance the effects of the radiation. [See these PRRT combination clinical trials.]
Sequencing treatments: comparing one treatment, such as PRRT, to another treatment to evaluate the order in which they should be given
For more on PRRT: