Part 1

• Introduction to RPT, Curriculum Overview and Radiobiology I ‒ Ana Kiess, MD, PhD
• Chemistry of Radiopharmaceuticals ‒ Freddy E. Escorcia, MD, PhD

Presenters introduce the curriculum, radiopharmaceutical therapies (RPTs) in general, radiobiology of RPTs, and chemistry of RPTs. This includes discussion of pharmacokinetics, biodistribution, dose rate, subcellular targeting, molecular and cellular effects of beta/alpha emitters, deterministic and stochastic effects, and toxicities.

Part 2

• Dosimetry I: Dosimetry Methods and Individual Dose Planning, Uncertainties ‒ Yuni Dewaraja, PhD
• Dosimetry II/Radiobiology II: Bioeffect Modeling, Toxicities, Alpha Emitters ‒ Robert F. Hobbs, PhD

The first presentation introduces methods for performing organ-level and voxel-level radiopharmaceutical therapy (RPT) dosimetry. The reference model-based MIRD formulism as well as direct Monte Carlo based methods for highly patient specific dose estimation using the patient’s SPECT and CT images as the input are discussed. The main steps of the dosimetry calculation including serial imaging, activity quantification, image registration, segmentation, time-activity fitting, and absorbed dose estimation are introduced together with the main sources of uncertainty. How individualized dosimetry before, during and after therapy can enhance RPT are covered. Methods for simplifying the dosimetry protocol to make it practical for clinical implementation are discussed including recently available AI-based tools.

In the second presentation, basic bio-effect modeling based on the linear-quadratic model is introduced. A large focus is on the biological effective dose (BED), how it is calculated, why it should be more utilized in RPT than in external beam (EBRT), and why it is a better correlate with outcome than absorbed dose. The presentation explores the theoretical comparison of EBRT and RPT doses and the limitations of that translation, especially with regard to normal organ toxicity threshold determination in RPT. Finally, the particularities and challenges of alphaRPTs are explored, including low count rate imaging, radioactive daughters, sub-organ dosimetry, the relative biological effect (RBE), and stochastic energy deposition.  

Part 3 

• Principles of Clinical Molecular Imaging for Radiopharmaceutical Therapy ‒ Vikas Prasad, MD, PhD
• Physics I: Image Acquisition and Quantitation (PET, SPECT) ‒ Rameshwar Prasad, MS, PhD
• Physics II: Instrumentation and Mathematics Pertaining to the Use and Measurement of Radioactivity ‒ Rameshwar Prasad, MS, PhD
• Physics III: Radiation Protection for Radiopharmaceutical Therapies ‒ Jessica Clements, MS
• Physics IV: Regulatory Issues and Standard Operating Procedures (SOP) ‒ Jacqueline Esthappan Zoberi, PhD

Imaging works as a gatekeeper for theranostics. The first presentation elucidates the significance of target (PSMA, somatostatin receptors) visualization, quantification and heterogeneity in treatment of patients with Lu-177 DOTATATE and Lu-177 PSMA. Methods for response assessments of Lu-177 PSMA and Lu-177 DOTATATE are also briefly discussed.

Molecular imaging using PET and SPECT is an increasingly used for cancer diagnosis, treatment, and treatment response evaluation. Recent progress in radiopharmaceutical therapy demands effective and quantitative PET and SPECT imaging application for seeing the cancer targets and visualizing what has been treated. In Physics I, principles of PET and SPECT imaging, challenges and application of quantitation are discussed.

Physics II covers principles of radioactivity and its measurement challenges. Various instruments for measuring and analyzing the radioactivity are also explained. 

Physics III covers some radiation safety basics related to starting up a new radiopharmaceutical therapy program. These include updating the facility radioactive materials license, patient screening and education along with some special situations presented by patients, management of household waste, preparing for treatment day, release criteria, and after-treatment care. 

Physics IV focuses on the development of standard operating procedures (SOPs) as one of a number of tasks for implementing a radiopharmaceutical therapy. In order to develop an SOP, one needs to learn about the therapy, allocate resources, and be familiar with radioactive material use regulations.

Part 4

• Principles of Patient-Centered Clinical Radiopharmaceutical Therapy: Quality and Safety ‒ Hyun Kim, MD

The session provides instruction on ensuring quality and safety in radiopharmaceutical programs. There are many unique considerations for quality assurance in radiopharmaceutical therapy, such as workflow checklists for treatment delivery and post-treatment dosimetry. Further, responses to medical emergencies require special planning to prevent contamination of the clinic and emergency response personnel.

Part 5

• Advancing Radiation Oncology Leadership in PSMA-Targeted Radiopharmaceutical Therapy ‒ Mallika Marar, MD, MBA
• Ra-223 for mCRPC ‒ Richard G. Stock, MD
• Therapy Specific Considerations for Radioactive Iodine ‒ Stephanie Markovina, MD, PhD and Nikhil Rammohan, MD, PhD
• Therapy-Specific Considerations for Liver-Directed Radiopharmaceutical Therapy/Selective Internal Radiation Therapy (⁹⁰Y) ‒ Andrew Kennedy, MD
• Radioligand Therapy NET ‒ Ravi Shridhar, MD, PhD

The first presentation reviews current indications for ¹⁷⁷Lu-PSMA-617 and practical considerations related to PSMA-directed RPTs including practice building and multidisciplinary patient management. Applications of pre-treatment molecular imaging with PSMA PET as part of the Theragnostic treatment paradigm will be discussed along with post-treatment imaging including SPECT. The presentation also explores topics related to further improving on prostate cancer clinical outcomes with PSMA-directed RPTs including ongoing clinical trials, dosimetry, and combination therapy including with external beam radiotherapy. A discussion of challenging clinical scenarios related to applying ¹⁷⁷Lu-PSMA-617 in the clinic is also included.

In the second presentation, the role of RA-233 and its applications are discussed.

The third presentation reviews the therapy-specific considerations for RAI toward the treatment of thyroid cancer. Discussion includes the basic mechanism, indications and toxicities of RAI therapy.

Hepatic brachytherapy using intra-arterial Y90 microspheres is a maturing therapy that often is delivered without the concomitant application of personalized dosimetry planning and post-treatment confirmatory dosimetry, multidisciplinary consultation, and collaborative management prior to and post liver-directed RPT. The fourth presentation reviews the eligibility criteria for liver-directed radiotherapy using Y90 and the estimated absorbed does in tumor and normal live prior to and after implementation.

The last presentation covers NET classification, incidence, survival; mechanism of action, renal protection; Lu-177-DOTATATE; NCCN guidelines on PRRT; clinical indications, sequencing; COMPETE Trial; other considerations such as dosimetry, delivery alphas, radioresistance); and community perspective.

Part 6

• Miscellaneous and Future Applications for Radiopharmaceutical Therapy / How To Become an Authorized User ‒ Michael Folkert, MD, PhD
• New Isotopes and Indications in Radiopharmaceutical Therapy ‒ Michael Folkert, MD, PhD

This session reviews miscellaneous and future applications of radiopharmaceutical therapy, many of which are under development or in use outside of the U.S. The presenter discusses radiopharmaceutical applications such as meta-iodobenzylguanidine (MIBG) therapy, topical rhenium skin cancer therapy, radiosynoviorthesis, palliative radiopharmaceutical therapies, indications in hematologic malignancies, and the increasing role of alpha emitters in radiopharmaceutical therapies. The presenter also touches on how to become an authorized user for administration of radiopharmaceutical therapies.