Part 1 - Introduction, Radiobiology I and Chemistry

• Introduction to Radiopharmaceutical Therapy and Curriculum Overview ‒ Ana Kiess, MD, PhD
• Radiobiology I (PK, Biodistribution, Dose Rate, Subcellular Targeting, Molecular and Cellular Effects of Beta/Alpha, Deterministic and Stochastic Effects, Toxicities) ‒ Ana Kiess, MD, PhD
• Chemistry of Radiopharmaceutical Therapies for Medical Use ‒ Freddy E. Escorcia, MD, PhD

In the first session, 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 and II and Radiobiology II

• Dosimetry I – Dosimetry Methods and Individual Dose Planning, Uncertainties ‒ Yuni Dewaraja, PhD
• Dosimetry II / Radiobiology II – Bioeffect Modeling, Tumor Dose-Response, Toxicities, Alpha Emitters ‒ Robert Francois 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 - Physics I and Principles of Clinical Molecular Imaging

• Physics I – Image Acquisition and Quantitation (PET, SPECT) ‒ Rameshwar Prasad, MS, PhD
• Principles of Clinical Molecular Imaging for Radiopharmaceutical Therapy ‒ Vikas Prasad, MD, PhD

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 the first presentation, principles of PET and SPECT imaging, challenges and application of quantitation are discussed.

Imaging works as a gatekeeper for theranostics. The second 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.

Part 4 - Physics II, III and IV

• 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 ‒ Jacqueline Esthappan Zoberi, PhD

The first presentation covers principles of radioactivity and its measurement challenges. Various instruments for measuring and analyzing the radioactivity are also explained. 

The second presentation 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. 

The third presentation 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 5 - Quality and Safety

• 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 6 - Therapy-Specific Considerations I

• Therapy-Specific Considerations for Lu-PSMA-617 ‒ Jeff M. Michalski, MD, MBA, FASTRO
• Therapy-Specific Considerations for Ra-223 ‒ Richard G. Stock, MD

In this session, the presenters review the role of prostate specific membrane antigen (PSMA) in the staging, localization, and targeting of prostate cancer. Diagnostic PET imaging agents such as 18F-piflufostat, 18F-flotufolastat, and 68Ga-gozetotide are allowing more accurate detection of early recurrent prostate cancer after either prior prostatectomy or definitive radiation therapy. They can also be used to select patients that may respond to radioligand therapy that employ similar PSMA-avid ligands that are linked to a therapeutic radioisotope. The first PSMA avid radioligand is 177Lu-vipivotide tetraxetan, which has been shown to prolong survival and maintain quality of life of men with castrate resistant prostate cancer. Clinical trials with similar drugs in various prostate cancer disease states are ongoing.

The role of RA-233 and its applications are also discussed.

Part 7 - Therapy-Specific Considerations II

• Therapy-Specific Considerations for RAI ‒ Stephanie Markovina, MD, PhD and Nikhil Rammohan, MD, PhD
• Therapy-Specific Considerations for Liver-Directed Radiopharmaceutical Therapy/Selective Internal Radiation Therapy ‒ Andrew S. Kennedy, MD

The first presentation, Therapy Specific Considerations for RAI, 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 second presentation, Therapy-Specific Considerations for Liver-Directed RPT/SIRT, 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.

Part 8 - Therapy-Specific Considerations III

• Therapy-Specific Considerations for Lu-DOTATATE ‒ Hyun Kim, MD

This session provides instruction on the clinical data and practical considerations for lutetium Lu 177 dotatate treatment.

Part 9 - Miscellaneous & Future Applications / Authorized User

• Miscellaneous and Future Applications of Radiopharmaceutical Therapy – How to Become an Authorized User, Meta-iodobenzylguanidine, Rhenium Skin Cancer Therapy, Radiosynoviorthesis, Alpha Emitters, Other ‒ 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. Presenters discuss 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. Presenters also touch on how to become an authorized user for administration of radiopharmaceutical therapies.