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.

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.

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.

Revisiting Prostate Cancer Recurrence with PSMA PET: Atlas of Typical and Atypical Patterns of Spread.

The introduction of prostate-specific membrane antigen (PSMA) in clinical practice has revolutionized evaluation of biochemical recurrence of prostate cancer after curative-intent treatment. The high expression of this glycoprotein in prostate cancer cells makes PSMA imaging superior to the current conventional staging methods, namely bone scanning and CT. The high capability of PSMA imaging for identifying very small previously undetected lesions has been widely demonstrated in the literature, leading to a rethinking of patient management by oncologists, urologists, and radiation oncologists. The typical and predictable patterns of spread in prostate cancer are still more prevalent, such as spread to pelvic lymph nodes and bone metastasis, but different patterns of disease spread are becoming more commonly recognized with higher reliability because PSMA imaging allows detection of more typical and atypical lesions than conventional imaging. Furthermore, it is important for the reading physician to recognize and understand the typical disease spread and the most prevalent atypical prostate cancer relapses, not only to heighten the relevancy of reports but also to improve imaging consultancy in multispecialty oncologic practice. ©RSNA, 2019.

General Concepts in Theranostics.

Theranostics describes the pairing of diagnostic biomarkers and therapeutic agents with common specific targets. Nuclear medicine is the greatest theranostics protagonist, relying on radioactive tracers for imaging biologic phenomena and delivering ionizing radiation to the tissues that take up those tracers. The concept has gained importance with the growth of personalized medicine, allowing customized management for diseases, refining patient selection, better predicting responses, reducing toxicity, and estimating prognosis. This work provides an overview of the general concepts of the theranostics approach in nuclear medicine discussing its background, features, and future directions in imaging and therapy.

Aberrant Hypermetabolism of Benign Uterine Leiomyoma on 18F-FDG PET/CT.

Leiomyomas are prevalent benign smooth muscle tumors in the uterus, displaying variable degrees of FDG uptake on PET/CT. The glucose metabolism intensity of those lesions relies on biologic features and markedly increased FDG accumulation is more typically related to malignant diseases, as in the case of leiomyosarcomas. Notwithstanding that uterine fibroids typically exhibit mild to moderate FDG uptake, in this article we report a case of unexpectedly intense hypermetabolism of a benign uterine leiomyoma on a PET/CT scan performed for initial staging of a breast cancer patient.

Analysis of the posterior cingulate cortex with [18F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods.

Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. OBJECTIVE: To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. METHODS: Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. RESULTS: The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. CONCLUSION: rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls.

Redução do metabolismo cerebral regional glicolítico (MRG) medido pela PET-18FDG no giro do cíngulo posterior (GCP) está relacionada a maior conversão para doença de Alzheimer (DA) em sujeitos com comprometimento cognitivo leve (CCL). Espectroscopia por ressonância magnética (MRS), um biomarcador promissor, demonstra redução de Naa/mI no GCP na DA. Raros estudos avaliam relações entre Naa/mI e MRG. OBJETIVO: Avaliar diferenças e possíveis correlações entre MRG com PET-18FDG e Naa/mI por MRS no GCP de sujeitos com DA, CCL e voluntários normais. MÉTODOS: Sujeitos com DA (N=32), CCL amnéstico (N=27) e voluntários idosos normais (GC, N=28), foram submetidos a PET-18FDG e análise de Naa/mI no GCP. A performance de ambos os métodos foi então comparada e verificou-se a existência de correlações entre os achados da PET e da MRS. RESULTADOS: Observou-se hipometabolismo glicolítico nos pacientes com DA no GCP em relação ao GC, porém não no CCL. A MRS demonstrou valores menores de Naa/mI no CP do grupo DA em relação ao GC, porém também sem diferenças entre CCL e GC. A área sob a curva ROC demonstrou valor de 0,70 para MRS e 0,93 para o MRG no GCP para diferenciar DA do GC. Houve correlação positiva entre o MRG e o Naa/mI no GCP. CONCLUSÃO: Os valores de metabolismo de glicose à PET e de Naa/mI à MRS no giro do cíngulo posterior apresentaram correlação positiva estatisticamente significante na presente amostra. Houve ainda superioridade da PET-18FDG para diferenciar DA do GC.

Analysis of the posterior cingulate cortex with [ 18 F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods / Análise do giro do cíngulo posterior com [ 18 f]FDG-PET e relação Naa/mI no comprometimento leve e na doença de Alzheimer: correlações e diferenças entre os métodos

ABSTRACT Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. OBJECTIVE To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. METHODS Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. RESULTS The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. CONCLUSION rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls.

RESUMO Redução do metabolismo cerebral regional glicolítico (MRG) medido pela PET-18FDG no giro do cíngulo posterior (GCP) está relacionada a maior conversão para doença de Alzheimer (DA) em sujeitos com comprometimento cognitivo leve (CCL). Espectroscopia por ressonância magnética (MRS), um biomarcador promissor, demonstra redução de Naa/mI no GCP na DA. Raros estudos avaliam relações entre Naa/mI e MRG. OBJETIVO Avaliar diferenças e possíveis correlações entre MRG com PET-18FDG e Naa/mI por MRS no GCP de sujeitos com DA, CCL e voluntários normais. MÉTODOS Sujeitos com DA (N=32), CCL amnéstico (N=27) e voluntários idosos normais (GC, N=28), foram submetidos a PET-18FDG e análise de Naa/mI no GCP. A performance de ambos os métodos foi então comparada e verificou-se a existência de correlações entre os achados da PET e da MRS. RESULTADOS Observou-se hipometabolismo glicolítico nos pacientes com DA no GCP em relação ao GC, porém não no CCL. A MRS demonstrou valores menores de Naa/mI no CP do grupo DA em relação ao GC, porém também sem diferenças entre CCL e GC. A área sob a curva ROC demonstrou valor de 0,70 para MRS e 0,93 para o MRG no GCP para diferenciar DA do GC. Houve correlação positiva entre o MRG e o Naa/mI no GCP. CONCLUSÃO Os valores de metabolismo de glicose à PET e de Naa/mI à MRS no giro do cíngulo posterior apresentaram correlação positiva estatisticamente significante na presente amostra. Houve ainda superioridade da PET-18FDG para diferenciar DA do GC.