Quarter Century PET/Computed Tomography Transformation of Oncology: Neuroendocrine Tumors.

Significant improvement in molecular imaging and theranostics in the management of neuroendocrine tumors (NETs) has been made in the last few decades. Somatostatin receptor-targeted PET imaging outperforms conventional, planar, and single-photon emission computed tomography imaging and is indicated in the evaluation of these patients when available, resulting in a significant impact on staging, treatment response assessment, and restaging of these patients. Radionuclide therapy can have an impact on patient outcome in metastatic disease when not many treatment options are available.

Joint EANM/SNMMI/IHPBA procedure guideline for [99mTc]Tc-mebrofenin hepatobiliary scintigraphy SPECT/CT in the quantitative assessment of the future liver remnant function.

PURPOSE: The aim of this joint EANM/SNMMI/IHPBA procedure guideline is to provide general information and specific recommendations and considerations on the use of [99mTc]Tc-mebrofenin hepatobiliary scintigraphy (HBS) in the quantitative assessment and risk analysis before surgical intervention, selective internal radiation therapy (SIRT) or before and after liver regenerative procedures. Although the gold standard to estimate future liver remnant (FLR) function remains volumetry, the increasing interest in HBS and the continuous request for implementation in major liver centers worldwide, demands standardization. METHODS: This guideline concentrates on the endorsement of a standardized protocol for HBS elaborates on the clinical indications and implications, considerations, clinical appliance, cut-off values, interactions, acquisition, post-processing analysis and interpretation. Referral to the practical guidelines for additional post-processing manual instructions is provided. CONCLUSION: The increasing interest of major liver centers worldwide in HBS requires guidance for implementation. Standardization facilitates applicability of HBS and promotes global implementation. Inclusion of HBS in standard care is not meant as substitute for volumetry, but rather to complement risk evaluation by identifying suspected and unsuspected high-risk patients prone to develop post-hepatectomy liver failure (PHLF) and post-SIRT liver failure.

99m Tc-MIBI SPECT/CT Evaluation of a Renal Collision Tumor.

ABSTRACT: Preoperative differentiation of oncocytomas from renal cell carcinoma (RCC) is often challenging. 99m Tc-MIBI imaging could play a potential role in differentiating oncocytoma from RCC, which in turn could guide surgical decision-making. We present the use of 99m Tc-MIBI SPECT/CT to characterize a renal mass in a 66-year-old man with a complex medical history, including history of bilateral oncocytomas. 99m Tc-MIBI SPECT/CT showed features suspicious of a malignant tumor, which was confirmed postnephrectomy as a chromophobe and papillary RCC collision tumor. This case supports 99m Tc-MIBI imaging for preoperative differentiation of benign versus malignant renal tumors.

Impact of 18 F-Fluciclovine PET/CT Findings on Failure-Free Survival in Biochemical Recurrence of Prostate Cancer Following Salvage Radiation Therapy.

PURPOSE: We aimed to evaluate the impact of 18 F-fluciclovine PET/CT imaging on failure-free survival (FFS) post-salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence. METHODS: Seventy-nine patients were recruited in a phase 2/3 clinical trial to undergo 18 F-fluciclovine PET/CT before SRT for PCa. Four patients with extrapelvic disease were excluded. All patients were followed up at regular intervals up to 48 months. Treatment failure was defined as a serum prostate-specific antigen level of ≥0.2 ng/mL above the nadir after SRT, confirmed with an additional measurement, requiring systemic treatment or clinical progression. Failure-free survival was computed and compared between patients grouped according to 18 F-fluciclovine PET/CT imaging findings. RESULTS: Eighty percent (60/75) of patients had a positive finding on 18 F-fluciclovine PET/CT, of which 56.7% (34/60) had prostate bed-only uptake, whereas 43.3% (26/60) had pelvic nodal ± bed uptake. Following SRT, disease failure was detected in 36% (27/75) of patients. There was a significant difference in FFS between patients who had a positive versus negative scan (62.3% vs 92.9% [ P < 0.001] at 36 months and 59.4% vs 92.9% [ P < 0.001] at 48 months). Similarly, there was a significant difference in FFS between patients with uptake in pelvic nodes ± bed versus prostate bed only at 36 months (49.8% vs 70.7%; P = 0.003) and at 48 months (49.8% vs 65.6%; P = 0.040). Failure-free survival was also significantly higher in patients with either negative PET/CT or prostate bed-only disease versus those with pelvic nodal ± prostate bed disease at 36 (78% vs 49.8%, P < 0.001) and 48 months (74.4% vs 49.8%, P < 0.001). CONCLUSIONS: Findings on pre-SRT 18 F-fluciclovine PET/CT imaging, even when acted upon to optimize the treatment decisions and treatment planning, are predictive of post-SRT FFS in men who experience PCa recurrence after radical prostatectomy. A negative 18 F-fluciclovine PET/CT is most predictive of a lower risk of failure, whereas the presence of pelvic nodal recurrence portends a higher risk of SRT failure.

Treatment Response to Lycopene in Recurrent Prostate Cancer Confirmed on 18 F-Fluciclovine PET/CT.

ABSTRACT: 18 F-fluciclovine (Axumin; Blue Earth Diagnostics, Ltd, Oxford, United Kingdom) PET has shown value in detecting biochemical recurrent prostatic cancer. Lycopene, a plant-based carotenoid, is reported to have potential inhibitory effect on prostate cancer, as a complementary treatment. We report a case of biochemically recurrent prostate cancer showing treatment response to lycopene as seen on an 18 F-fluciclovine PET/CT correlating with serum prostate-specific antigen response.

PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0.

Here we aim to provide updated guidance and standards for the indication, acquisition, and interpretation of PSMA PET/CT for prostate cancer imaging. Procedures and characteristics are reported for a variety of available PSMA small radioligands. Different scenarios for the clinical use of PSMA-ligand PET/CT are discussed. This document provides clinicians and technicians with the best available evidence, to support the implementation of PSMA PET/CT imaging in research and routine practice.

Paragangliomas and Pheochromocytomas: Positron Emission Tomography/Computed Tomography Diagnosis and Therapy.

Molecular imaging evaluation of pheochromocytomas and paragangliomas depends on multiple factors, such as localized versus metastatic disease, the genetic, and biochemical profile of tumors. Positron emission tomography/computed tomography (PET/CT) imaging of these tumors outperforms Meta-Iodo-Benzyl-Guanidine (MIBG) scintigraphy in most cases. A few PET radiotracers have been studied in evaluating these patients with somatostatin receptor PET imaging and have shown superior performance compared with other agents in most of these patients. 18F-fluorodeoxyglucose PET/CT imaging is useful in select patients, such as those with succinate dehydrogenase complex subunit B-associated disease. Treatment strategy depends on multiple factors and necessitates a multidisciplinary approach.

Differences in Failure-Free Survival After Salvage Radiotherapy Guided by Conventional Imaging Versus 18F-Fluciclovine PET/CT in Postprostatectomy Patients: A Post Hoc Substratification Analysis of the EMPIRE-1 Trial.

The EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement 1) trial reported a survival advantage in recurrent prostate cancer salvage radiotherapy (SRT) guided by 18F-fluciclovine PET/CT versus conventional imaging. We performed a post hoc analysis of the EMPIRE-1 cohort stratified by protocol-specified criteria, comparing failure-free survival (FFS) between study arms. Methods: EMPIRE-1 randomized patients to SRT planning via either conventional imaging only (bone scanning plus abdominopelvic CT or MRI) (arm A) or conventional imaging plus 18F-fluciclovine PET/CT (arm B). Randomization was stratified by prostate-specific antigen (PSA) level (<2.0 vs. ≥ 2.0 ng/mL), adverse pathology, and androgen-deprivation therapy (ADT) intent. We subdivided patients in each arm using the randomization stratification criteria and compared FFS between patient subgroups across study arms. Results: Eighty-one and 76 patients received per-protocol SRT in study arms A and B, respectively. The median follow-up was 3.5 y (95% CI, 3.0-4.0). FFS was 63.0% and 51.2% at 36 and 48 mo, respectively, in arm A and 75.5% at both 36 and 48 mo in arm B. Among patients with a PSA of less than 2 ng/mL (mean, 0.42 ± 0.42 ng/mL), significantly higher FFS was seen in arm B than arm A at 36 mo (83.2% [95% CI, 70.0-91.0] vs. 66.5% [95% CI, 51.6-77.8], P < 0.001) and 48 mo (83.2% [95% CI, 70.0-91.0] vs. 56.2% [95% CI, 40.5-69.2], P < 0.001). No significant difference in FFS between study arms in patients with a PSA of at least 2 ng/mL was observed. Among patients with adverse pathology, significantly higher FFS was seen in arm B than arm A at 48 mo (68.9% [95% CI, 52.1-80.8] vs. 42.8% [95% CI, 26.2-58.3], P < 0.001) though not at the 36-mo follow-up. FFS was higher in patients without adverse pathology in arm B versus arm A (90.2% [95% CI, 65.9-97.5] vs. 73.1% [95% CI, 42.9-89.0], P = 0.006) at both 36 and 48 mo. Patients in whom ADT was intended in arm B had higher FFS than those in arm A, with the difference reaching statistical significance at 48 mo (65.2% [95% CI, 40.3-81.7] vs. 29.1 [95% CI, 6.5-57.2], P < 0.001). Patients without ADT intent in arm B had significantly higher FFS than patients in arm A at 36 mo (80.7% [95% CI, 64.9-90.0] vs. 68.0% [95% CI, 51.1-80.2]) and 48 mo (80.7% [95% CI, 64.9-90.0] vs. 58.6% [95% CI, 41.0-72.6]). Conclusion: The survival advantage due to the addition of 18F-fluciclovine PET/CT to SRT planning is maintained regardless of the presence of adverse pathology or ADT intent. Including 18F-fluciclovine PET/CT to SRT leads to survival benefits in patients with a PSA of less than 2 ng/mL but not in patients with a PSA of 2 ng/mL or higher.

18F-Fluciclovine PET/CT: A Potential Imaging Biomarker for the Evaluation of Multiple Myeloma.

ABSTRACT: Incidental concomitant second primary malignancy may be detected on PET/CT imaging. We present an 18F-fluciclovine PET/CT of a patient undergoing evaluation of biochemically recurrent prostate cancer with incidental radiotracer uptake within lytic osseous lesions confirmed to be multiple myeloma. We present the 18F-fluciclovine PET/CT images of an 83-year-old man with prostate cancer treated in 2005 who presented with back pain and a CT scan revealing multiple lytic osseous lesions concerning for metastases versus a plasma cell neoplasm. Prostate-specific antigen at the time of evaluation was 0.1 ng/mL.

18F-FDG PET/CT for Response Assessment in Lung Cancer.

Treatment response assessment in lung cancer is crucial in the management strategy and outcome of patients. Accurate treatment response assessment can guide the treating physicians and improve patient survival. Anatomic and metabolic tumor response assessments have been evaluated extensively, showing a positive impact in the management of these patients. 18F-FDG PET/CT provides early and more specific treatment response assessments, preceding anatomic changes in these tumors. Familiarity with the different treatment response assessment algorithms, criteria, time intervals, imaging pitfalls is essential for treating physicians and nuclear radiologists to provide accurate response assessments. Artificial Intelligence is being more frequently explored for this purpose and can assist physicians in providing prompt and accurate treatment response assessments.

Predictors and Real-World Use of Prostate-Specific Radioligand Therapy: PSMA and Beyond.

PSMA is a transmembrane protein that is markedly overexpressed in prostate cancer, making it an excellent target for imaging and treating patients with prostate cancer. Several small molecule inhibitors and antibodies of PSMA have been radiolabeled for use as therapeutic agents and are currently under clinical investigation. PSMA-based radionuclide therapy is a promising therapeutic option for men with metastatic prostate cancer. The phase II TheraP study demonstrated superior efficacy, lower side effects, and improved patient-reported outcomes compared with cabazitaxel. The phase III VISION study demonstrated that radionuclide therapy with ß-emitter 177Lu-PSMA-617 can prolong survival and improve quality of life when offered in addition to standard-of-care therapy in men with PSMA-positive metastatic castration-resistant prostate cancer whose disease had progressed with conventional treatments. Nevertheless, up to 30% of patients have inherent resistance to PSMA-based radionuclide therapy, and acquired resistance is inevitable. Hence, strategies to increase the efficacy of PSMA-based radionuclide therapy have been under clinical investigation. These include better patient selection; increased radiation damage delivery via dosimetry-based administered dose or use of α-emitters instead of ß-emitters; or using combinatorial approaches to overcome radioresistance mechanisms (innate or acquired), such as with novel hormonal agents, PARP inhibitors, or immunotherapy.

PET Imaging of Oral Cavity and Oropharyngeal Cancers.

Fluorine-18 fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) plays an important role in the staging, treatment planning, treatment response assessment, detecting recurrent disease, and predicting prognosis in patients with oral cavity and oropharyngeal squamous cell carcinoma. PET/CT has advantage especially in the detection of nodal, distant metastatic disease and second primary malignancy. PET/MR provides superior soft tissue contrast while decreasing radiation exposure, which is advantageous in evaluation of the primary tumor.

Incidental Spinal Meningioma on an 18F-Fluciclovine PET/CT.

ABSTRACT: Incidental PET radiotracer uptake is not infrequently encountered in PET/CT imaging. We present the 18F-fluciclovine PET/CT of a 60-year-old man undergoing evaluation of biochemically recurrent prostate cancer with incidental radiotracer uptake in the thoracic spinal canal, which was proven to be a World Health Organization grade I spinal meningioma on surgical pathology. 18F-fluciclovine and 18F-FDG PET/CT images of a 60-year-old man with biochemically recurrent prostate cancer prostate cancer with a prostate-specific antigen of 14.4 ng/mL, 7 years after primary external beam radiation followed by a prostate-specific antigen nadir of 1.6 ng/mL, are presented.

Imaging of Cancer Immunotherapy: Response Assessment Methods, Atypical Response Patterns, and Immune-Related Adverse Events, From the AJR Special Series on Imaging of Inflammation.

The introduction of immunotherapy with immune-checkpoint inhibitors (ICIs) has revolutionized cancer treatment paradigms. Since FDA approval of the first ICI in 2011, multiple additional ICIs have been approved and granted marketing authorization, and many promising agents are in early clinical adoption. Due to the distinctive biologic mechanisms of ICIs, the patterns of tumor response and progression seen with immunotherapy differ from those observed with cytotoxic chemothera-pies. With increasing clinical adoption of immunotherapy, it is critical for radiologists to recognize different response patterns and common pitfalls to avoid misinterpretation of imaging studies or prompt premature cessation of potentially effective treatment. This review provides an overview of ICIs and their mechanisms of action and discusses anatomic and metabolic immune-related response assessment methods, typical and atypical patterns of immunotherapy response (including pseudoprogression, hyperprogression, dissociated response, and durable response), and common imaging features of immune-related adverse events. Future multicenter trials are needed to validate the proposed immune-related response criteria and identify the functional imaging markers of early treatment response and survival.

Clinical utility of 18F-Fluciclovine PET/CT in recurrent prostate cancer with very low (≤0.3 ng/mL) prostate-specific antigen levels.

The purpose of this study was to evaluate 18F-fluciclovine PET/CT detection rates in the evaluation of biochemical recurrence in prostate cancer patients with very low (≤0.3 ng/mL) serum prostate-specific antigen (PSA) levels following definitive treatment. Prostate cancer patients with biochemical recurrence and very low serum PSA (≤0.3 ng/mL) who underwent clinical 18F-fluciclovine PET/CT were included in this single-institution retrospective study. PET/CT clinical reports at the time of interpretation were reviewed and categorized as positive or negative. In patients who had further evaluation with imaging and/or biopsy, the results were recorded to determine the true detection rate. Of the 64 eligible patients with very low serum PSA (median serum PSA of 0.17 ng/mL), 57.8% (37/64) scans were categorized as positive. Stratified by PSA levels, positivity rates were 43.8% (7/16), 60.0% (15/25) and 65.2% (15/23) for PSA<0.1 ng/mL, 0.1-<0.2 ng/mL and 0.2-≤0.3 ng/mL, respectively. The most common location of disease was the prostate bed (73%), followed by pelvic lymph nodes (22%) and distant disease (14%). In the small subset of patients who had further evaluation after a positive study (n=7), all had confirmed disease with a positive predictive value of 100%. In conclusion, among prostate cancer patients with biochemical recurrence, 18F-fluciclovine PET/CT is useful in patients with very low serum PSA of ≤0.3 ng/mL, with a 57.8% positivity rate, higher than previously reported. Though standard of truth could only be ascertained in 19% (7/37) of patients with a positive study, the positive predictive value was 100%.

PET Imaging for Head and Neck Cancers.

Head and neck cancers are commonly encountered cancers in clinical practice in the United States. Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT has been clinically applied in staging, occult primary tumor detection, treatment planning, response assessment, follow-up, recurrent disease detection, and prognosis prediction in these patients. Alternative PET tracers remain investigational and can provide additional valuable information such as radioresistant tumor hypoxia. The recent introduction of 18F-FDG PET/MR imaging has provided the advantage of combining the superior soft tissue resolution of MR imaging with the functional information provided by 18F-FDG PET. This article is a concise review of recent advances in PET imaging in head and neck cancer.

Constellation of Von Hippel-Lindau Disease-Related Findings on a 68Ga-DOTATATE PET/CT.

ABSTRACT: Von Hippel-Lindau (VHL) is a rare predominantly hereditary syndrome characterized by multiple benign and malignant tumors that can affect different organ systems. We present representative images of a 68Ga-DOTATATE PET/CT in a patient with confirmed VHL gene mutation, which demonstrates a constellation of findings commonly seen in these patients in one single imaging modality.

Ring Sclerosis in Prostate Cancer: Circle of Malignancy or Benignity?

ABSTRACT: Prostate cancer osteoblastic metastases may have different morphologies, and some of these may overlap with certain benign bone lesions. In this series of 5 prostate cancer patients, we describe bone lesions with central lucency and surrounding peripheral sclerosis and their varying appearances on different imaging modalities. Although prostate cancer metastases are commonly associated with sclerotic lesions, they can also present as osteolytic or lucent lesions, and these lesions should be carefully evaluated. The findings emphasize the importance of correlation with prior imaging, comparing findings on different imaging techniques and follow-up to differentiate benign disease from metastatic disease in these situations.