Logistical, technical, and radiation safety aspects of establishing a radiopharmaceutical therapy program: A case in Lutetium-177 prostate-specific membrane antigen (PSMA) therapy.

Prostate-specific membrane antigen (PSMA) is a cell surface protein highly expressed in nearly all prostate cancers, with restricted expression in some normal tissues. The differential expression of PSMA from tumor to non-tumor tissue has resulted in the investigation of numerous targeting strategies for therapy of patients with metastatic prostate cancer. In March of 2022, the FDA granted approval for the use of lutetium-177 PSMA-617 (Lu-177-PSMA-617) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy.

First-in-Humans Evaluation of Safety and Dosimetry of Cu-LLP2A for PET Imaging.

There remains an unmet need for molecularly targeted imaging agents for multiple myeloma (MM). The integrin very late antigen 4 (VLA4), is differentially expressed in malignant MM cells and in pathogenic inflammatory microenvironmental cells. [Cu]Cu-CB-TE1A1P-LLP2A (Cu-LLP2A) is a VLA4-targeted, high-affinity radiopharmaceutical with promising utility for managing patients diagnosed with MM.

Radiopharmaceutical Quality Control Considerations for Accelerator-Produced Actinium Therapies.

Alpha-particle-emitting radiotherapies are of great interest for the treatment of disseminated cancer. Actinium-225 (Ac) produces four α-particles through its decay and is among the most attractive radionuclides for use in targeted radiotherapy applications. However, supply issues for this isotope have limited availability and increased cost for research and translation.

[Zr]Trastuzumab: Evaluation of Radiation Dosimetry, Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer.

Purpose: The purpose of the present study is to evaluate safety, human radiation dosimetry, and optimal imaging time of [Zr]trastuzumab in patients with HER2-positive breast cancer.

Procedures: Twelve women with HER2-positive breast cancer underwent [Zr]trastuzumab positron emission tomography (PET)/X-ray computed tomography (CT) twice within 7 days post-injection. Biodistribution data from whole-torso PET/CT images and organ time-activity curves were created using data from all patients.

The role of exploratory investigational new drugs for translating radiopharmaceuticals into first-in-human studies.

The Food and Drug Administration has provided a mechanism to reduce time and resources expended on new pharmaceuticals, including radiopharmaceuticals, in order to identify the most promising agents for further development. The exploratory investigational new drug guidance describes early phase 1 exploratory approaches involving microdoses of potential drug candidates that are consistent with regulatory requirements while maintaining the safety needed for human subjects, allowing sponsors to move ahead more quickly with the development of new agents.