Reassessing Patterns of Response to Immunotherapy with PET: From Morphology to Metabolism.

Cancer demands precise evaluation and accurate and timely assessment of response to treatment. Imaging must be performed early during therapy to allow adjustments to the course of treatment. For decades, cross-sectional imaging provided these answers, showing responses to the treatment through changes in tumor size. However, with the emergence of immune checkpoint inhibitors, complex immune response patterns were revealed that have quickly highlighted the limitations of this approach. Patterns of response beyond tumor size have been recognized and include cystic degeneration, necrosis, hemorrhage, and cavitation. Furthermore, new unique patterns of response have surfaced, like pseudoprogression and hyperprogression, while other patterns were shown to be deceptive, such as unconfirmed progressive disease. This evolution led to new therapeutic evaluation criteria adapted specifically for immunotherapy. Moreover, inflammatory adverse effects of the immune checkpoint blockade were identified, many of which were life threatening and requiring prompt intervention. Given complex concepts like tumor microenvironment and novel therapeutic modalities in the era of personalized medicine, increasingly sophisticated imaging techniques are required to address the intricate patterns of behavior of different neoplasms. Fluorine 18-fluorodeoxyglucose PET/CT has rapidly emerged as one such technique that spans both molecular biology and immunology. This imaging technique is potentially capable of identifying and tracking prognostic biomarkers owing to its combined use of anatomic and metabolic imaging, which enables it to characterize biologic processes in vivo. This tailored approach may provide whole-body quantification of the metabolic burden of disease, providing enhanced prediction of treatment response and improved detection of adverse events. ©RSNA, 2020.

Theranostics in Nuclear Medicine: Emerging and Re-emerging Integrated Imaging and Therapies in the Era of Precision Oncology.

Theranostics refers to the pairing of diagnostic biomarkers with therapeutic agents that share a specific target in diseased cells or tissues. Nuclear medicine, particularly with regard to applications in oncology, is currently one of the greatest components of the theranostic concept in clinical and research scenarios. Theranostics in nuclear medicine, or nuclear theranostics, refers to the use of radioactive compounds to image biologic phenomena by means of expression of specific disease targets such as cell surface receptors or membrane transporters, and then to use specifically designed agents to deliver ionizing radiation to the tissues that express these targets. The nuclear theranostic approach has sparked increasing interest and gained importance in parallel to the growth in molecular imaging and personalized medicine, helping to provide customized management for various diseases; improving patient selection, prediction of response and toxicity, and determination of prognosis; and avoiding futile and costly diagnostic examinations and treatment of many diseases. The authors provide an overview of theranostic approaches in nuclear medicine, starting with a review of the main concepts and unique features of nuclear theranostics and aided by a retrospective discussion of the progress of theranostic agents since early applications, with illustrative cases emphasizing the imaging features. Advanced concepts regarding the role of fluorine 18-fluorodeoxyglucose PET in theranostics, as well as developments in and future directions of theranostics, are discussed. ©RSNA, 2020 See discussion on this article by Greenspan and Jadvar.

Prostate-specific Membrane Antigen PET: Therapy Response Assessment in Metastatic Prostate Cancer.

Therapy response assessment is a critical step in cancer management, leading clinicians to optimize the use of therapeutic options during the course of the disease. Imaging is a pivotal biomarker for therapy response evaluation in oncology and has gained wider use through the development of reproducible data-based guidelines, of which the Response Evaluation Criteria in Solid Tumors is the most successful example. Disease-specific criteria have also been proposed, and the Prostate Cancer Working Group 3 criteria are the mainstay for prostate cancer (PC). However, conventional imaging evaluation in metastatic PC has several limitations, including (a) the inability to detect small-volume disease, (b) the high prevalence of bone (nonmeasurable) lesions at imaging, and (c) the established role of serum prostate-specific antigen (PSA) levels as the biomarker of choice for response assessment and disease progression. In addition, there are an increasing number of newer treatment options with various effects on imaging features. Prostate-specific membrane antigen (PSMA) PET has improved patient selection for newer treatments, such as metastasis-directed therapy (MDT) or radionuclide therapy. The role of PSMA PET in response assessment for many metastatic PC therapeutic options (MDT, androgen deprivation therapy, chemotherapy, radionuclide therapy, and immunotherapy) is an evolving issue, with emerging data showing good correlation with PSA levels and clinical outcome. However, there are specific implications of each therapy (especially androgen deprivation therapy and immunotherapy) on PSMA expression by PC cells, leading to potential pitfalls and inaccuracies that must be known by radiologists. Despite some limitations, PSMA PET is addressing gaps left by conventional imaging methods (eg, CT and bone scanning) and nonimaging biomarkers (PSA levels) in metastatic PC therapy response assessment, a role that can be improved with advances like refinement of interpretation criteria and whole-body tumor burden quantification.© RSNA, 2020See discussion on this article by Barwick and Castellucci.