Role of PET/Computed Tomography in Gastric and Colorectal Malignancies.

This article focuses on the role of PET/computed tomography in evaluating and managing gastric cancer and colorectal cancer. The authors start with describing the common aspects of imaging with 2-deoxy-2-18F-d-glucose, followed by tumor-specific discussions of gastric and colorectal malignancies. Finally, the authors provide a brief overview of non-FDG tracers including their potential clinical applications, and describe future directions in imaging these malignancies.

ACR Appropriateness Criteria® Right Upper Quadrant Pain: 2022 Update.

Acute right upper quadrant pain is one of the most common presenting symptoms in hospital emergency departments, as well as outpatient settings. Although gallstone-related acute cholecystitis is a leading consideration in diagnosis, a myriad of extrabiliary sources including hepatic, pancreatic, gastroduodenal, and musculoskeletal should also be considered. This document focuses on the diagnostic accuracy of imaging studies performed specifically to evaluate acute right upper quadrant pain, with biliary etiologies including acute cholecystitis and its complications being the most common. An additional consideration of extrabiliary sources such as acute pancreatitis, peptic ulcer disease, ascending cholangitis, liver abscess, hepatitis, and painful liver neoplasms remain a diagnostic consideration in the right clinical setting. The use of radiographs, ultrasound, nuclear medicine, CT, and MRI for these indications are discussed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Image acquisition and interpretation of 18F-DCFPyL (piflufolastat F 18) PET/CT: How we do it.

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) is rapidly becoming widely accepted as the standard-of-care for imaging of men with prostate cancer. Labeled indications for regulatoryapproved agents include primary staging and recurrent disease in men at risk of metastases. The first commercial PSMA PET agent to become available was 18F-DCFPyL (piflufolastat F 18), a radiofluorinated small molecule with high-affinity for PSMA. The regulatory approval of 18F-DCFPyL hinged upon two key, multi-center, registration trials, OSPREY (patient population: highrisk primary staging) and CONDOR (patient population: biochemical recurrence). In this manuscript, we will (1) review key findings from the OSPREY and CONDOR trials, (2) discuss the clinical acquisition protocol we use for 18F-DCFPyL PET scanning, (3) present information on important pearls and pitfalls, (4) provide an overview of the PSMA reporting and data system (PSMA-RADS) interpretive framework, and (5) posit important future directions for research in PSMA PET. Our overall goal is to provide a brief introduction for practices and academic groups that are adopting 18F-DCFPyL PET scans for use in their patients with prostate cancer.

18F-DCFPyL (PSMA) PET as a radiotherapy response assessment tool in metastatic prostate cancer.

Background: Prostate Specific Membrane Antigen (PSMA) - positron emission tomography (PET) guides metastasis-directed radiotherapy (MDRT) in prostate cancer (PrCa). However, its value as a treatment response assessment tool after MDRT remains unclear. Importantly, there is limited understanding of the potential of radiotherapy (RT) to alter PSMA gene (folate hydrolase 1; FOLH1) expression. Methodology: We reviewed a series of 11 men with oligo-metastatic PrCa (25 metastasis sites) treated with MDRT before re-staging with 18F-DCFPyL (PSMA) PET upon secondary recurrence. Acute effects of RT on PSMA protein and mRNA levels were examined with qPCR and immunoblotting in human wild-type androgen-sensitive (LNCap), castrate-resistant (22RV1) and castrate-resistant neuroendocrine (PC3 and DU145) PrCa cell lines. Xenograft tumors were analyzed with immunohistochemistry. Further, we examined PSMA expression in untreated and irradiated radio-resistant (RR) 22RV1 (22RV1-RR) and DU145 (DU145-RR) cells and xenografts selected for survival after high-dose RT. Results: The majority of MDRT-treated lesions showed lack of PSMA-PET/CT avidity, suggesting treatment response even after low biological effective dose (BED) MDRT. We observed similar high degree of heterogeneity of PSMA expression in both human specimens and in xenograft tumors. PSMA was highly expressed in LNCap and 22RV1 cells and tumors but not in the neuroendocrine PC3 and DU145 models. Single fraction RT caused detectable reduction in PSMA protein but not in mRNA levels in LNCap cells and did not significantly alter PSMA protein or mRNA levels in tissue culture or xenografts of the other cell lines. However, radio-resistant 22RV1-RR cells and tumors demonstrated marked decrease of PSMA transcript and protein expression over their parental counterparts. Conclusions: PSMA-PET may be a promising tool to assess RT response in oligo-metastatic PrCa. However, future systematic investigation of this concept should recognize the high degree of heterogeneity of PSMA expression within prostate tumors and the risk for loss of PSMA expression in tumor surviving curative courses of RT.

Intra-individual comparison of 18F-sodium fluoride PET-CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial.

BACKGROUND: Detection of skeletal metastases in patients with prostate cancer or breast cancer remains a major clinical challenge. We aimed to compare the diagnostic performance of 99mTc-methylene diphosphonate (99mTc-MDP) single-photon emission CT (SPECT) and 18F-sodium fluoride (18F-NaF) PET-CT for the detection of osseous metastases in patients with high-risk prostate or breast cancer. METHODS: MITNEC-A1 was a prospective, multicentre, single-cohort, phase 3 trial conducted in ten hospitals across Canada. Patients aged 18 years or older with breast or prostate cancer with a WHO performance status of 0-2 and with high risk or clinical suspicion for bone metastasis, but without previously documented bone involvement, were eligible. 18F-NaF PET-CT and 99mTc-MDP SPECT were done within 14 days of each other for each participant. Two independent reviewers interpreted each modality without knowledge of other imaging findings. The primary endpoint was the overall accuracy of 99mTc-MDP SPECT and 18F-NaF PET-CT scans for the detection of bone metastases in the per-protocol population. A combination of histopathological, clinical, and imaging follow-up for up to 24 months was used as the reference standard to assess the imaging results. Safety was assessed in all enrolled participants. This study is registered with ClinicalTrials.gov, NCT01930812, and is complete. FINDINGS: Between July 11, 2014, and March 3, 2017, 290 patients were screened, 288 of whom were enrolled (64 participants with breast cancer and 224 with prostate cancer). 261 participants underwent both 18F-NaF PET-CT and 99mTc-MDP SPECT and completed the required follow-up for statistical analysis. Median follow-up was 735 days (IQR 727-750). Based on the reference methods used, 109 (42%) of 261 patients had bone metastases. In the patient-based analysis, 18F-NaF PET-CT was more accurate than 99mTc-MDP SPECT (84·3% [95% CI 79·9-88·7] vs 77·4% [72·3-82·5], difference 6·9% [95% CI 1·3-12·5]; p=0·016). No adverse events were reported for the 288 patients recruited. INTERPRETATION: 18F-NaF has the potential to displace 99mTc-MDP as the bone imaging radiopharmaceutical of choice in patients with high-risk prostate or breast cancer. FUNDING: Canadian Institutes of Health Research.

PSMA PET/CT guided intensification of therapy in patients at risk of advanced prostate cancer (PATRON): a pragmatic phase III randomized controlled trial.

BACKGROUND: Positron emission tomography targeting the prostate specific membrane antigen (PSMA PET/CT) has demonstrated unparalleled performance as a staging examination for prostate cancer resulting in substantial changes in management. However, the impact of altered management on patient outcomes is largely unknown. This study aims to assess the impact of intensified radiotherapy or surgery guided by PSMA PET/CT in patients at risk of advanced prostate cancer. METHODS: This pan-Canadian phase III randomized controlled trial will enroll 776 men with either untreated high risk prostate cancer (CAPRA score 6-10 or stage cN1) or biochemically recurrent prostate cancer post radical prostatectomy (PSA > 0.1 ng/mL). Patients will be randomized 1:1 to either receive conventional imaging or conventional plus PSMA PET imaging, with intensification of radiotherapy or surgery to newly identified disease sites. The primary endpoint is failure free survival at 5 years. Secondary endpoints include rates of adverse events, time to next-line therapy, as well as impact on health-related quality of life and cost effectiveness as measured by incremental cost per Quality Adjusted Life Years gained. DISCUSSION: This study will help create level 1 evidence needed to demonstrate whether or not intensification of radiotherapy or surgery based on PSMA PET findings improves outcomes of patients at risk of advanced prostate cancer in a manner that is cost-effective. TRIAL REGISTRATION: This trial was prospectively registered in ClinicalTrials.gov as NCT04557501 on September 21, 2020.

Effect of 18F-DCFPyL PET/CT on the Management of Patients with Recurrent Prostate Cancer: Results of a Prospective Multicenter Registry Trial.

Background The high positivity rate of prostate-specific membrane antigen (PSMA) PET in the setting of biochemical failure (BCF), even when conventional imaging is negative, is promising. Purpose To assess the disease detection rate of PSMA-based PET/CT with fluorine 18-DCFPyL as a radiotracer and the PET-directed management change in men with suspected limited recurrent prostate cancer. Materials and Methods This prospective multicenter registry (Ontario PSMA-PET Registry for Recurrent Prostate Cancer, or PREP) enrolled men with BCF after primary therapy (radical prostatectomy plus or minus salvage radiation therapy or primary radiation therapy) and zero to four disease sites at conventional imaging (CT and bone scintigraphy). The positivity rate of PSMA PET according to serum prostate-specific antigen (PSA) level; frequency of local-egional, oligometastatic, and extensive metastatic recurrence; and rate of change in management after PET findings were recorded. The nonparametric Mood median test was used to assess the association between serum PSA level and change in management. Results A total of 1289 men (median age, 71 years [interquartile range, 65-75 years]) were evaluated. PSMA PET helped detect disease in 841 of 1289 men (65%) and in 615 of 999 men (62%) with negative conventional imaging. The recurrence detection rates according to serum PSA level at enrollment were 38% (160 of 424 men), 63% (107 of 171 men), and 83% (573 of 692 men) for PSA under 0.5 ng/mL, 0.5-1.0 ng/mL, and above 1.0 ng/mL, respectively. At PSMA PET, 399 of 1289 men (31%) had local-regional recurrence, 314 (24%) had oligometastatic disease, and 128 (10%) had extensive metastases. Following PET examination, a change in planned management was recorded in 748 of 1289 men (58%), and in 371 of 1250 men (30%), there was a change in management intent, more commonly from palliative to potentially curative intent (255 of 1289 men [20%]). Conclusion Prostate-specific membrane antigen PET helped detect additional sites of disease compared with conventional imaging in approximately 60% of men with biochemical failure and suspected low-volume metastatic disease, resulting in frequent change in management, including a change from palliative to curative or radical intent therapy in 20% of men. Long-term follow-up is needed to determine whether this impacts disease control. Clinical trial registration no. NCT03718260 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Civelek in this issue.

Management of Differentiated Thyroid Cancer: The Standard of Care.

In the past decade, the management of differentiated thyroid cancer (DTC) underwent a paradigm shift toward the use of risk stratification with the goal of maximizing the benefit and minimizing the morbidity of radioiodine (131I) therapy. 131I therapy is guided by information derived from surgical histopathology, molecular markers, postoperative diagnostic radioiodine scintigraphy, and thyroglobulin levels. 131I is used for diagnostic imaging and therapy of DTC based on physiologic sodium-iodine symporter expression in normal and neoplastic thyroid tissue. We summarize the essential information at the core of multidisciplinary DTC management, which emphasizes individualization of 131I therapy according to the patient's risk for tumor recurrence.

Defining radio-recurrent intra-prostatic target volumes using PSMA-targeted PET/CT and multi-parametric MRI.

PURPOSE: Our purpose was to evaluate intra-prostatic cancer volumes for salvage radiotherapy in men with recurrent prostate cancer confined to the prostate post-primary radiotherapy using mpMRI and 18F-DCFPyL PET/CT (PET). METHODS: Men with biochemical failure post-primary radiotherapy were enrolled in a multi-centre trial investigating mpMRI and PET. All men with isolated intra-prostatic recurrence are included in this secondary analysis. The intra-prostatic gross tumour volume (GTV) was manually delineated on mpMRI and was also delineated on PET using three methods: 1. manually, 2. using a 30% threshold of maximum intra-prostatic standard uptake value (SUVmax), and 3. using a 67% threshold of this SUVmax. Clinical target volumes (CTV) including expansions on each GTV were generated. Conformity indices were performed between the mpMRI CTV and each PET CTV. Correlation with biopsy and clinical outcomes were performed. RESULTS: Of the 36 men included, 30 (83%) had disease in two quadrants or less using the combination of mpMRI and PET. Mean target volume (union of CTV on mpMRI and CTV manually delineated on PET) was 12.2 cc (49% of prostate gland volume). 12/36 (33%) men had a biopsy. Per-patient sensitivity was 91% for mpMRI and 82% for PET. CONCLUSIONS: mpMRI and PET provide complementary information for delineation of intra-prostatic recurrent disease. Union of CTV on mpMRI and PET is often less than 50% of the prostate, suggesting this imaging could help define a target for focal salvage therapy.

Clinical Applications of Artificial Intelligence in Positron Emission Tomography of Lung Cancer.

The ability of a computer to perform tasks normally requiring human intelligence or artificial intelligence (AI) is not new. However, until recently, practical applications in medical imaging were limited, especially in the clinic. With advances in theory, microelectronic circuits, and computer architecture as well as our ability to acquire and access large amounts of data, AI is becoming increasingly ubiquitous in medical imaging. Of particular interest to our community, radiomics tries to identify imaging features of specific pathology that can represent, for example, the texture or shape of a region in the image. This is conducted based on a review of mathematical patterns and pattern combinations. The difficulty is often finding sufficient data to span the spectrum of disease heterogeneity because many features change with pathology as well as over time and, among other issues, data acquisition is expensive. Although we are currently in the early days of the practical application of AI to medical imaging, research is ongoing to integrate imaging, molecular pathobiology, genetic make-up, and clinical manifestations to classify patients into subgroups for the purpose of precision medicine, or in other words, predicting a priori treatment response and outcome. Lung cancer is a functionally and morphologically heterogeneous disease. Positron emission tomography (PET) is an imaging technique with an important role in the precision medicine of patients with lung cancer that helps predict early response to therapy and guides the selection of appropriate treatment. Although still in its infancy, early results suggest that the use of AI in PET of lung cancer has promise for the detection, segmentation, and characterization of disease as well as for outcome prediction.

Role of Artificial Intelligence in Theranostics:: Toward Routine Personalized Radiopharmaceutical Therapies.

We highlight emerging uses of artificial intelligence (AI) in the field of theranostics, focusing on its significant potential to enable routine and reliable personalization of radiopharmaceutical therapies (RPTs). Personalized RPTs require patient-specific dosimetry calculations accompanying therapy. Additionally we discuss the potential to exploit biological information from diagnostic and therapeutic molecular images to derive biomarkers for absorbed dose and outcome prediction; toward personalization of therapies. We try to motivate the nuclear medicine community to expand and align efforts into making routine and reliable personalization of RPTs a reality.

Update on Molecular Imaging and Precision Medicine in Lung Cancer.

Precision medicine integrates molecular pathobiology, genetic make-up, and clinical manifestations of disease in order to classify patients into subgroups for the purposes of predicting treatment response and suggesting outcome. By identifying those patients who are most likely to benefit from a given therapy, interventions can be tailored to avoid the expense and toxicity of futile treatment. Ultimately, the goal is to offer the right treatment, to the right patient, at the right time. Lung cancer is a heterogeneous disease both functionally and morphologically. Further, over time, clonal proliferations of cells may evolve, becoming resistant to specific therapies. PET is a sensitive imaging technique with an important role in the precision medicine algorithm of lung cancer patients. It provides anatomo-functional insight during diagnosis, staging, and restaging of the disease. It is a prognostic biomarker in lung cancer patients that characterizes tumoral heterogeneity, helps predict early response to therapy, and may direct the selection of appropriate treatment.

Artificial intelligence for molecular neuroimaging.

In recent years, artificial intelligence (AI) or the study of how computers and machines can gain intelligence, has been increasingly applied to problems in medical imaging, and in particular to molecular imaging of the central nervous system. Many AI innovations in medical imaging include improving image quality, segmentation, and automating classification of disease. These advances have led to an increased availability of supportive AI tools to assist physicians in interpreting images and making decisions affecting patient care. This review focuses on the role of AI in molecular neuroimaging, primarily applied to positron emission tomography (PET) and single photon emission computed tomography (SPECT). We emphasize technical innovations such as AI in computed tomography (CT) generation for the purposes of attenuation correction and disease localization, as well as applications in neuro-oncology and neurodegenerative diseases. Limitations and future prospects for AI in molecular brain imaging are also discussed. Just as new equipment such as SPECT and PET revolutionized the field of medical imaging a few decades ago, AI and its related technologies are now poised to bring on further disruptive changes. An understanding of these new technologies and how they work will help physicians adapt their practices and succeed with these new tools.

Somatostatin Receptor Imaging and Theranostics: Current Practice and Future Prospects.

A new era of precision diagnostics and therapy for patients with neuroendocrine neoplasms began with the approval of somatostatin receptor (SSTR) radiopharmaceuticals for PET imaging followed by peptide receptor radionuclide therapy (PRRT). With the transition from SSTR-based γ-scintigraphy to PET, the higher sensitivity of the latter raised questions regarding the direct application of the planar scintigraphy-based Krenning score for PRRT eligibility. Also, to date, the role of SSTR PET in response assessment and predicting outcome remains under evaluation. In this comprehensive review article, we discuss the current role of SSTR PET in all aspects of neuroendocrine neoplasms, including its relation to conventional imaging, selection of patients for PRRT, and the current understanding of SSTR PET-based response assessment. We also provide a standardized reporting template for SSTR PET with a brief discussion.

Canadian Urological Association best practice report: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and PET/magnetic resonance (MR) in prostate cancer.

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) is increasingly being used worldwide as part of the clinical workup for men with prostate cancer. With high overall accuracy for the detection of prostate cancer, PSMA-targeted PET has an increasingly established role in the setting of biochemical failure after primary therapy and an evolving role in the setting of initial disease staging; its utility for guiding management in the setting of metastatic disease is less clear. Although the specificity is high, familiarization with potential pitfalls in the interpretation of PSMA-targeted PET, including knowledge of the causes for false-positive and negative examinations, is critical. The aim of this best practice report is to provide an illustrative discussion of the current and evolving clinical indications for PSMA-targeted PET, as well as a review of physiological radiopharmaceutical biodistribution and potential imaging pitfalls.