Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired radiopharmaceuticals to image and selectively treat various cancers. The clinical use of theranostics has increased in recent years, with U.S. Food and Drug Administration (FDA) approval of lutetium 177 (¹⁷⁷Lu) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) and ¹⁷⁷Lu-prostate-specific membrane antigen vector-based radionuclide therapies. The field of theranostics has imminent potential for emerging clinical applications. This article reviews critical areas of active clinical advancement in theranostics, including forthcoming clinical trials advancing FDA-approved and emerging radiopharmaceuticals, approaches to dosimetry calculations, imaging of different radionuclide therapies, expanded indications for currently used theranostic agents to treat a broader array of cancers, and emerging ideas in the field. Keywords: Molecular Imaging, Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, Molecular Imaging-Target Development, PET/CT, SPECT/CT, Radionuclide Therapy, Dosimetry, Oncology, Radiobiology © RSNA, 2023.

Visual ⁶⁸Ga-PSMA-11 PET/CT eligibility criteria helped identify participants with metastatic castration-resistant prostate cancer who benefitted from ¹⁷⁷Lu-PSMA-617 therapy in the VISION trial, with higher ⁶⁸Ga-PSMA-11 uptake associated with improved outcomes.

Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (²²⁵actinium, ²¹²lead, and ²¹¹astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic.

An approach to the use of lutetium 177 gallium 68 tetraazacyclododecane tetraacetic acid octreotate peptide receptor radionuclide therapy (PRRT), an effective treatment for advanced gastroenteropan... Lutetium 177 (177Lu) DOTA-0-Tyr3-Octreotate (DOTATATE) peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced gastroenteropancreatic neuroendocrine tumors. This review ...

The aim of this narrative review is to evaluate the current status of ¹⁷⁷Lu-PSMA (prostate specific membrane antigen) therapy for metastatic castration-resistant prostate cancer (mCRPC) in the light of the current literature. We also addressed patient preparation, therapy administration and side effect profiles. ¹⁷⁷Lu-PSMA therapy efficacy was assessed by using prospective trials, meta-analyses and major retrospective trials. Predictors of efficacy were also mentioned. Although there are some different approaches regarding the use of ¹⁷⁷Lu-PSMA therapy in different countries, this type of therapy is generally safe, with a low toxicity profile. From the oncological point of view, a PSA (prostate specific antigen) decline of ≥50% was seen in 10.6–69% of patients with mCRPC; whereas progression-free survival (PFS) was reported to be 3–13.7 months in different studies. Consequently, ¹⁷⁷Lu-PSMA therapy is a promising treatment in patients with mCRPC, with good clinical efficacy, even in heavily pretreated patients with multiple lines of systemic therapy. Currently, there are ongoing clinical trials in the United States, including a phase III multicenter FDA registration trial.