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Theranostics describes the coupling of a diagnostic biomarker and a therapeutic agent (i.e., a theranostic pair) that share a common target in tumor cells or their microenvironment. The term is increasingly associated with in vivo nuclear medicine oncologic applications that couple diagnostic imaging from gamma radiation with concomitant localized high-energy particulate radiation to a tissue expressing the common target. Several theranostic pairs have been translated into clinical practice in the United States and are poised to become a mainstay for cancer treatment. This article reviews experience to date with theranostics for solid-organ malignancies, addressing the practical integration into care pathways of beta-emitting therapies that include somatostatin analog radioligands for neuroendocrine tumors, prostate-specific membrane antigen-directed therapy for prostate cancer, and 131I-MIBG therapy for tumors of neural crest origin. Toxicities related to theranostics administration, as well as indications for therapy cessation in patients who experience adverse events, are also discussed. A multidisciplinary team-based approach for identifying patients most likely to respond to these agents, determining the optimal time for therapy delivery, and managing their care throughout the therapy course, is critical to the success of a radiotheranostic program.

Prostate-specific membrane antigen (PSMA) theranostics has been a momentous triumph for nuclear medicine. The recent approvals of PSMA-targeted imaging agents (

Background The aim of this exploratory preclinical study was to evaluate the efficacy of 18F-FMAU PET in quantitatively measuring response to a chemotherapeutic agent in experimental prostate cancer models. Methods and Materials: Docetaxel (DTX) ‒ a standard therapy agent in castrate-resistant metastatic prostate cancer was used as the chemotherapy drug. Athymic male nu/nu mice were inoculated with PC-3 cells in the right flank. After the tumor diameter reached 5 mm, DTX (24 mg/kg) was injected intravenously twice/week, whereas the control group was intravenously administered with saline. During the therapeutic period, the tumor size and body weight were monitored, and longitudinal PET scans were acquired with 18F-FMAU to evaluate tumor cell proliferation. 18F-FMAU PET scans were performed at 2 h post-injection of 18F-FMAU on days 0, 11, 18, and 22. Biodistribution studies were carried out after the PET scan on day 22. Results Consecutive administrations of DTX were effective in inhibiting PC-3 tumor growth compared to the control group. For PET imaging, PC-3 tumor uptake of 18F-FMAU in the treatment group was increased significantly from 3.09 ± 0.60%ID/g (day 0) to 5.32 ± 0.37%ID/g (day 22), whereas the 18F-FMAU tumor update in the control group remained relatively similar on day 0 (2.37 ± 0.51%ID/g) vs. day 22 (1.83 ± 0.22%ID/g). The tumor-to-muscle uptake ratio of 18F-FMAU was increased from 2.63 ± 0.20 (day 0) to 5.91 ± 1.1 (day 22) in the treatment group. On day 22, no statistical significance was observed on the tumor-to-muscle uptake ratio of 18F-FMAU in the treatment group vs. the control group. The tumor-to-liver uptake ratio of 18F-FMAU was also similar on day 22 in the treatment group (4.29 ± 0.09) vs. the control group (3.83 ± 0.59). Conclusion 18F-FMAU uptake in implanted PC-3 tumors increases with DTX treatment despite the decline in tumor size. Further investigation is needed to decipher the underlying biological mechanism of this flare effect and its relation to the predictability of therapy response.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumors, and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumor such as prostate cancer requires the expansion of existing and the establishment of new theranostics centers. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostic centers. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.

Metastatic prostate cancer is not curable. There have been major strides in the treatment of patients with castration-resistant prostate cancer with many available therapeutic options which generally prolong the overall survival about an average of 4 months. The more recent advances are in immunotherapy and targeted radionuclide therapy, which are the focus of this chapter. We review the current evidence in these arenas and comment on future developments that are anticipated to transform the treatment landscape of patients with metastatic prostate cancer.