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[18F]-JK-PSMA-7 PET/CT Under Androgen Deprivation Therapy in Advanced Prostate Cancer.
Dietlein, F, Mueller, P, Kobe, C, Endepols, H, Hohberg, M, Zlatopolskiy, BD, Krapf, P, Heidenreich, A, Neumaier, B, Drzezga, A, et al
Molecular imaging and biology. 2021;(2):277-286
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Abstract
PURPOSE PSMA imaging is frequently used for monitoring of androgen deprivation therapy (ADT) in prostate cancer. In a previous study, [18F]-JK-PSMA-7 exhibited favorable properties for tumor localization after biochemical recurrence. In this retrospective study, we evaluated the performance of [18F]-JK-PSMA-7 under ADT. PROCEDURES We examined the performance of [18F]-JK-PSMA-7 in 70 patients (first cohort) with increasing or detectable PSA values under ADT (PSA < 2 ng/ml for 21/70 patients). We further analyzed 58 independent patients with PSA levels < 2 ng/ml under ADT, who were imaged with [68Ga]PSMA-11 or [18F]DCFPyL (second cohort). Finally, we compared detection rates between [18F]-JK-PSMA-7, [68Ga]PSMA-11, and [18F]DCFPyL. RESULTS In the first cohort, we detected [18F]-JK-PSMA-7-positive lesions in 63/70 patients. In patients with PSA levels ≥ 2 ng/ml, the detection rate was 100 % (49/49). In patients with PSA < 2 ng/ml, the detection rate was significantly lower (66.7 %, 14/21, p = 9.7 × 10-5) and dropped from 85.7 % (12/14, PSA levels between 0.3 and 2.0 ng/ml) to 28.6 % (2/7) for PSA levels < 0.3 ng/ml (p = 1.73 × 10-2). In the second cohort (PSA < 2 ng/ml), the detection rate was 79.3 % (46/58) for [68Ga]PSMA-11 or [18F]DCFPyL. Again, the detection rate was significantly higher (p = 1.1 × 10-2) for patients with PSA levels between 0.3 and 2.0 ng/ml (87.0 %, 40/46) relative to those with PSA levels < 0.3 ng/ml (50 %, 6/12). No significant difference was found between [18F]-JK-PSMA-7 and [68Ga]PSMA-11 or [18F]DCFPyL in patients with PSA levels < 2 ng/ml (p = 0.4295). CONCLUSION [18F]-JK-PSMA-7 PET showed a high detection rate in patients with PSA levels ≥ 0.3 ng/ml under ADT. The lower PSA threshold of 0.3 ng/ml for high detection rates was consistent across the three PSMA ligands. Thus, PSMA imaging is suitable for clinical follow-up of patients with increasing PSA levels under ADT.
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PET Imaging for Head and Neck Cancers.
Marcus, C, Sheikhbahaei, S, Shivamurthy, VKN, Avey, G, Subramaniam, RM
Radiologic clinics of North America. 2021;(5):773-788
Abstract
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.
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Series of myocardial FDG uptake requiring considerations of myocardial abnormalities in FDG-PET/CT.
Minamimoto, R
Japanese journal of radiology. 2021;(6):540-557
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Abstract
Distinct from cardiac PET performed with preparation to control physiological FDG uptake in the myocardium, standard FDG-PET/CT performed with 4-6 h of fasting will show variation in myocardial FDG uptake. For this reason, important signs of myocardial and pericardial abnormality revealed by myocardial FDG uptake tend to be overlooked. However, recognition of possible underlying disease will support further patient management to avoid complications due to the disease. This review demonstrates the mechanism of FDG uptake in the myocardium, discusses the factors affecting uptake, and provides notable image findings that may suggest underlying disease.
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Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus: The SIMPLE Trial.
Jürgens, M, Schou, M, Hasbak, P, Kjær, A, Wolsk, E, Zerahn, B, Wiberg, M, Brandt-Jacobsen, NH, Gæde, P, Rossing, P, et al
Journal of the American Heart Association. 2021;(15):e020418
Abstract
Background Sodium-glucose cotransporter 2 inhibitors reduce hospitalizations for heart failure and cardiovascular death, although the underlying mechanisms have not been resolved. The SIMPLE trial (The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus) investigated the effects of empagliflozin on myocardial flow reserve (MFR) reflecting microvascular perfusion, in patients with type 2 diabetes mellitus at high cardiovascular disease risk. Methods and Results We randomized 90 patients to either empagliflozin 25 mg once daily or placebo for 13 weeks, as add-on to standard therapy. The primary outcome was change in MFR at week 13, quantified by Rubidium-82 positron emission tomography/computed tomography. The secondary key outcomes were changes in resting rate-pressure product adjusted MFR, changes to myocardial flow during rest and stress, and reversible cardiac ischemia. Mean baseline MFR was 2.21 (95% CI, 2.08-2.35). There was no change from baseline in MFR at week 13 in either the empagliflozin: 0.01 (95% CI, -0.18 to 0.21) or placebo groups: 0.06 (95% CI, -0.15 to 0.27), with no treatment effect -0.05 (95% CI, -0.33 to 0.23). No effects on the secondary outcome parameters by Rubidium-82 positron emission tomography/computed tomography was observed. Treatment with empagliflozin reduced hemoglobin A1c by 0.76% (95% CI, 1.0-0.5; P<0.001) and increased hematocrit by 1.69% (95% CI, 0.7-2.6; P<0.001). Conclusions Empagliflozin did not improve MFR among patients with type 2 diabetes mellitus and high cardiovascular disease risk. The present study does not support that short-term improvement in MFR explains the reduction in cardiovascular events observed in the outcome trials. Registration URL: https://clinicaltrialsregister.eu/; Unique identifier: 2016-003743-10.
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Utility of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Visceral Leishmaniasis: Case Report and Literature Review.
Pinnegar, HP, Sánchez-Montalvá, A, Barios Profitos, M, Bosch-Nicolau, P, Salvador, F, Molina, I
The American journal of tropical medicine and hygiene. 2021;(3):934-944
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Abstract
The diagnosis of visceral leishmaniasis (VL) is complicated and often unsuspected. Little is known of the usefulness of nuclear imaging in VL. Our objective was to describe findings seen in fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in cases of VL. We retrospectively reviewed VL cases diagnosed at Vall d'Hebron University Hospital from May 2012 to May 2018 and selected those that had an FDG-PET/CT performed. Information on procedures and details of the FDG-PET/CT features and follow-up were collected. We then systematically reviewed the literature on VL and FDG-PET/CT. Four of 43 patients diagnosed with VL had an FDG-PET/CT performed. All four patients presented diffuse splenic uptake of FDG-PET/CT. Adenopathy was not always present, and bone marrow uptake was found in two patients. A posttreatment FDG-PET/CT in one patient revealed normalization of initial findings. In the literature review, 43 of 50 cases presented similar splenic uptake in the PET/CT, being described as different patterns: "increased metabolism," "homogeneous," "diffuse," "diffuse and multifocal," "nodular," "patchy and granular," "subcortical," and "compatible with lymphoma." Other frequent findings were bone marrow uptake and adenopathies. We, therefore, conclude that FDG-PET/CT could become a useful tool for the diagnosis and follow-up of VL and that VL should be taken into account in patients with fever of unknown origin with enhanced splenic uptake in FDG-PET/CT. Differential diagnosis in these cases should be made with splenic primary lymphoma, virus infections, chemotherapy, and colony-stimulating factor therapy. Further structured studies with more cases are needed to define its diagnostic and prognostic value.
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18F-sodium fluoride positron emission tomography (NaF-18-PET/CT) radiomic signatures to evaluate responses to alpha-particle Radium-223 dichloride therapy in osteosarcoma metastases.
Kairemo, K, Roszik, J, Anderson, P, Ravizzini, G, Rao, A, Macapinlac, HA, Subbiah, V
Current problems in cancer. 2021;(5):100797
Abstract
Patients with osteoblastic metastases from high risk osteosarcoma continue to have a poor prognosis after progression from standard-of-care multi-agent chemotherapy. In a first-in-human dose escalation trial of bone targeted Radium 223 dichloride alpha-particle therapy in 18 patients with advanced osteosarcoma only 1 patient responded based on conventional Response Evaluation Criteria in Solid Tumors (RECIST). Na18F PET response Criteria in Solid Tumors(NAFCIST), based on Sodium fluoride-18 (Na18F) positron emission tomography (PET)-CT was developed to better evaluate bone specific response. To further appreciate the spatial and temporal heterogeneity of the partial or mixed responses, a radiomics method was developed. Analyses were performed with 18F-sodium fluoride positron emission tomography imaging studies before and after alpha-particle therapy. Radioactive 18F- -atom concentrations were measured in soft-tissues, in approximately 1000 concentration data points for 18F- per 1 cm3 metastatic tumor. Data was analyzed from the SUV intensity values, the histogram of intensities and entropy values. Radiomics may inform intra-tumoral and inter-tumoral heterogeneity in response of bone forming osteosarcoma to alpha particle therapy. Each patient (and each tumor) represents an "N of 1" case and warrants in depth analysis individually.
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Assessment of Total-Body Atherosclerosis by PET/Computed Tomography.
Høilund-Carlsen, PF, Piri, R, Gerke, O, Edenbrandt, L, Alavi, A
PET clinics. 2021;(1):119-128
Abstract
Atherosclerotic burden has become the focus of cardiovascular risk assessment. PET/computed tomography (CT) imaging with the tracers 18F-fluorodeoxyglucose and 18F-sodium fluoride shows arterial wall inflammation and microcalcification, respectively. Arterial uptake of both tracers is modestly age dependent. 18F-sodium fluoride uptake is consistently associated with risk factors and more easily measured in the heart. Because of extremely high sensitivity, ultrashort acquisition, and minimal radiation to the patient, total-body PET/CT provides unique opportunities for atherosclerosis imaging: disease screening and delayed and repeat imaging with global disease scoring and parametric imaging to better characterize the atherosclerosis of individual patients.
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Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [64Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.
Jensen, JK, Zobel, EH, von Scholten, BJ, Rotbain Curovic, V, Hansen, TW, Rossing, P, Kjaer, A, Ripa, RS
Frontiers in endocrinology. 2021;:790405
Abstract
BACKGROUND Quantification of coronary artery inflammation and atherosclerosis remains a challenge in high-risk individuals. In this study we sought to investigate if the glucagon like peptide-1 receptor agonist liraglutide has a direct anti-inflammatory effect in the coronary arteries using positron emission tomography (PET) with a radioactive tracer targeting activated macrophages in the vessel-wall. METHODS Thirty randomly selected participants with type 2 diabetes from the placebo-controlled trial LIRAFLAME were enrolled in this sub-study. Participants were, prior to enrollment in this sub-study, randomized to either treatment with daily liraglutide (n=15) or placebo (n=15). Both groups underwent a combined [64Cu]Cu-DOTATATE positron emission tomography and computed tomography scan of the heart at baseline and after 26 weeks of treatment. Coronary artery uptake of [64Cu]Cu-DOTATATE were measured as maximum standardized uptake values (SUVmax); and means of the maximum values (mSUVmax), both values were calculated at the level of each participant and each individual coronary-segment. RESULTS SUVmax and mSUVmax values decreased significantly in the liraglutide group both at the participant level (SUVmax: p=0.013; mSUVmax: p=0.004) and at the coronary-segment level (SUVmax: p=0.001; mSUVmax: p<0.0001). No change was observed in the placebo group neither at the participant level (SUVmax: p=0.69; mSUVmax: p=0.67) or at the coronary-segment level (SUVmax: p=0.49; mSUVmax: p=0.30). When comparing the mean change in uptake values between the two groups at both the participant level (SUVmax: p=0.076; mSUVmax: p=0.077) and the coronary segment level (SUVmax: p=0.13; mSUVmax: p=0.11) a borderline significant difference was observed. Baseline SUVmax [64Cu]Cu-DOTATATE uptake values showed a weak positive correlation with the inflammatory biomarker high-sensitivity c-reactive protein (τ =0.26, p=0.045). CONCLUSION Liraglutide treatment for 26-weeks caused a significant reduction in [64Cu]Cu-DOTATATE uptake in the coronary arteries whereas this was not seen in the placebo treated group. In addition, [64Cu]Cu-DOTATATE PET/CT as a marker of coronary inflammation correlated with the systemic inflammation marker hs-CRP.
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Detection Rate of Prostate Specific Membrane Antigen Tracers for Positron Emission Tomography/Computerized Tomography in Prostate Cancer Biochemical Recurrence: A Systematic Review and Network Meta-Analysis.
Crocerossa, F, Marchioni, M, Novara, G, Carbonara, U, Ferro, M, Russo, GI, Porpiglia, F, Di Nicola, M, Damiano, R, Autorino, R, et al
The Journal of urology. 2021;(2):356-369
Abstract
PURPOSE Restaging of prostate cancer in patients with biochemical recurrence after radical treatment remains a challenging clinical scenario as current imaging modalities are suboptimal. To date, prostate specific membrane antigen positron emission tomography/computerized tomography seems to represent a very promising diagnostic tool in this setting. Therefore, we evaluated the detection rate of several positron emission tomography/computerized tomography prostate specific membrane antigen based tracers in the restaging of prostate cancer in patients with biochemical recurrence. MATERIALS AND METHODS According to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, a systematic search was performed across MEDLINE®, Embase® and Web of Science™. PICOS (Patient, Intervention, Comparator, Outcome, Study Type), criteria consisted of P: patients with biochemical recurrence after radical prostatectomy and/or radiation therapy as primary treatment; I: studies using gallium-68-prostate specific membrane antigen-11, gallium-68-prostate specific membrane antigen inhibitor for imaging and therapy, gallium-68-trishydroxypyridinone-prostate specific membrane antigen, copper-64-prostate specific membrane antigen-617, fluorine-18-DCFPyL or fluorine-18-prostate specific membrane antigen-1007; C: no control group or positron emission tomography/computerized tomography comparative studies; O: patient specific overall detection rate; and S: retrospective/prospective studies. A meta-analysis of proportions and a network meta-analysis were performed. Heterogeneity was assessed using Cochran Q and I2 statistics. Quality was assessed by QUADAS-2 (University of Bristol, Bristol, United Kingdom). Funnel plots and Egger test were used for publication biases. RESULTS A total of 43 studies including 5,832 patients were identified and included in the analysis. An overall detection rate of 74.1% (95% CI 69.2%-78.5%) was found, with no differences between tracers. The overall detection rates were 33.7%, 50.0%, 62.8%, 73.1% and 91.7% % in prostate specific antigen subgroups of less than 0.2 ng/ml, 0.2 to 0.49 ng/ml, 0.50 to 0.99 ng/ml, 1.0 to 1.99 ng/ml, and 2.0 ng/ml or greater, respectively. No difference between tracers was found according to prostate specific antigen doubling time or prostate specific antigen velocity. No tracer proved superior to the others through network meta-analysis. High heterogeneity and inconsistency were found across all analyses. Included studies showed a low risk of bias. CONCLUSIONS Prostate specific membrane antigen positron emission tomography/computerized tomography for prostate cancer restaging in patients with biochemical recurrence achieves best detection rates (over 70%) if prostate specific antigen is below 1 ng/ml. At lower prostate specific antigen levels the detection rate of prostate specific membrane antigen positron emission tomography/computerized tomography is lower (33.7% for levels below 0.2 ng/ml and 50% for levels 0.2 to 0.49 ng/ml), despite being better than "older" tracers such as choline based positron emission tomography or computerized tomography/bone scintigraphy. Furthermore, no prostate specific membrane antigen tracer can be currently considered superior to others. Further studies are needed to better define the diagnostic performance and role of these imaging techniques.
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Role of 18F-Fluciclovine and Prostate-Specific Membrane Antigen PET/CT in Guiding Management of Oligometastatic Prostate Cancer: AJR Expert Panel Narrative Review.
Savir-Baruch, B, Choyke, PL, Rowe, SP, Schuster, DM, Subramaniam, RM, Jadvar, H
AJR. American journal of roentgenology. 2021;(4):851-859
Abstract
Twenty-five years ago, oligometastatic disease was proposed as an intermediary clinical state of cancer with unique implications for therapies that may impact cancer evolution and patient outcome. Identification of limited metastases that are potentially amenable to targeted therapies fundamentally depends on the sensitivity of diagnostic tools, including new-generation imaging methods. For men with biochemical recurrence after definitive therapy of the primary prostate cancer, PET/CT using either the FDA-approved radiolabeled amino acid analogue 18F-fluciclovine or investigational radiolabeled agents targeting prostate-specific membrane antigen (PSMA) enables identification of early metastases at lower serum PSA levels than was previously feasible using conventional imaging. Evidence supports PSMA PET/CT as the most sensitive imaging modality available for identifying disease sites in oligometastatic prostate cancer. PSMA PET/CT will likely become the modality of choice after regulatory approval and will drive the development of trials of emerging metastasis-directed therapies such as stereotactic ablative body radiation and radioguided surgery. Indeed, numerous ongoing or planned clinical trials are studying advances in management of oligometastatic prostate cancer based on this heightened diagnostic capacity. In this rapidly evolving clinical environment, radiologists and nuclear medicine physicians will play major roles in facilitating clinical decision making and management of patients with oligometastatic prostate cancer.