The early efforts at PRRT were done with a form of Indium-111. This form of radiation was found to have a very short radius of action, causing little or no collateral damage to nearby tissue, but was most effective on very small tumors. Doctors using the Indium-111 found that it was not ideal for PRRT because the small particle range resulted in short tissue penetration and limited effectiveness on tumors 2cm and larger.

In the late 1990s and early 2000s, Doctors started using two other radionuclides that were coupled to Octreotide. These were Yttrium-90 and Lutetium-177. Later some doctors tried a combination of these two radionuclides (done in sequence). Both of these radionuclides are stronger than the Indium-111 and have longer tissue penetration. The Y-90 has the longest tissue penetration and therefore is commonly used to treat patients with larger tumors. One rule of thumb used to ascertain which isotope to use says that tumors from 2cm to 4cm should be treated with Lutetium-177 while tumors 4cm and larger should be treated with Yttrium-90.