PSMA and Choline PET for the Assessment of Response to Therapy and Survival Outcomes in Prostate Cancer Patients: A Systematic Review from the Literature.

The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2) determine the value of both tracers for the prediction of response to therapy and survival outcomes in prostate cancer. We performed a systematic literature search in PubMed/Scopus/Google Scholar/Cochrane/EMBASE databases (between January 2010 and October 2021) accordingly. The quality of the included studies was evaluated following the "Quality Assessment of Prognostic Accuracy Studies" tool (QUAPAS-2). We selected 40 articles: 23 articles discussed the use of PET imaging with [68Ga]PSMA-11 (16 articles/1123 patients) or [11C]/[18F]Choline (7 articles/356 patients) for the prediction of response to radiotherapy (RT) and survival outcomes. Seven articles (three with [68Ga]PSMA-11, three with [11C]Choline, one with [18F]Choline) assessed the role of PET imaging in the evaluation of response to docetaxel (as neoadjuvant therapy in one study, as first-line therapy in five studies, and as a palliative regimen in one study). Seven papers with radiolabeled [18F]Choline PET/CT (n = 121 patients) and three with [68Ga]PSMA-11 PET (n = 87 patients) were selected before and after enzalutamide/abiraterone acetate. Finally, [18F]Choline and [68Ga]PSMA-11 PET/CT as gatekeepers for the treatment of metastatic prostate cancer with Radium-223 were assessed in three papers. In conclusion, in patients undergoing RT, radiolabeled choline and [68Ga]PSMA-11 have an important prognostic role. In the case of systemic therapies, the role of such new-generation imaging techniques is still controversial without sufficient data, thus requiring additional in this scenario.

The Role of Molecular Imaging in the Assessment of Cardiac Amyloidosis: State-of-the-Art.

Cardiac amyloidosis is a progressive infiltrative disease for which new treatments are now available. As therapy should be started as early as possible to avoid complications such as restrictive cardiomyopathy, arrhythmias and heart failure, a prompt and reliable diagnosis by means of non-invasive tests would be highly warranted. Electrocardiography, echocardiography and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy, but none of these modalities can effectively differentiate the cardiac amyloid subtypes. We aim to highlight the most relevant findings in the literature of molecular imaging in the assessment of patients with cardiac amyloidosis and to underline future clinical perspective. We performed multiple searches using Pub-Med databases in order to find important original articles on the role of molecular imaging in the assessment of patients affected by CA. Several search terms were used, such as "cardiac amyloidosis"; "Light-chain amyloidosis"; "Transthyretin amyloid cardiomyopathy"; "bone scintigraphy"; "single photon emission tomography" or "SPECT"; "Positron emission tomography or PET", and "cardiac imaging". All radiopharmaceuticals tracing cardiac amyloidosis were also included. Several studies about the role of SPECT with bone-seeking tracer (47 articles) and innervation tracer (9 articles) in the work-up of CA, as well as new PET amyloid-binding (14 articles) and bone radiotracer (4 articles) have been reviewed and discussed. Molecular imaging represents a sensitive tool for early assessment of both amyloid burden and cardiac innervation, to differentiate between subtypes and to monitor disease burden, disease progression, and potential response to therapy.

Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial.

IMPORTANCE: In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging. OBJECTIVE: To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard. MAIN OUTCOMES AND MEASURES: Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety. RESULTS: A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients. CONCLUSIONS AND RELEVANCE: Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.

Impact of a Bayesian penalized likelihood reconstruction algorithm on image quality in novel digital PET/CT: clinical implications for the assessment of lung tumors.

BACKGROUND: The aim of this study was to evaluate and compare PET image reconstruction algorithms on novel digital silicon photomultiplier PET/CT in patients with newly diagnosed and histopathologically confirmed lung cancer. A total of 45 patients undergoing 18F-FDG PET/CT for initial lung cancer staging were included. PET images were reconstructed using ordered subset expectation maximization (OSEM) with time-of-flight and point spread function modelling as well as Bayesian penalized likelihood reconstruction algorithm (BSREM) with different ß-values yielding a total of 7 datasets per patient. Subjective and objective image assessment with all image datasets was carried out, including subgroup analyses for patients with high dose (> 2.0 MBq/kg) and low dose (≤ 2.0 MBq/kg) of 18F-FDG injection regimen. RESULTS: Subjective image quality ratings were significantly different among all different reconstruction algorithms as well as among BSREM using different ß-values only (both p < 0.001). BSREM with a ß-value of 600 was assigned the highest score for general image quality, image sharpness, and lesion conspicuity. BSREM reconstructions resulted in higher SUVmax of lung tumors compared to OSEM of up to + 28.0% (p < 0.001). BSREM reconstruction resulted in higher signal-/ and contrast-to-background ratios of lung tumor and higher signal-/ and contrast-to-noise ratio compared to OSEM up to a ß-value of 800. Lower ß-values (BSREM450) resulted in the best image quality for high dose 18F-FDG injections, whereas higher ß-values (BSREM600) lead to the best image quality in low dose 18F-FDG PET/CT (p < 0.05). CONCLUSIONS: BSREM reconstruction algorithm used in digital detector PET leads to significant increases of lung tumor SUVmax, signal-to-background ratio, and signal-to-noise ratio, which translates into a higher image quality, tumor conspicuity, and image sharpness.

In-depth analysis of interreader agreement and accuracy in categorical assessment of brown adipose tissue in (18)FDG-PET/CT.

PURPOSE: To evaluate the interreader agreement of a three-tier craniocaudal grading system for brown fat activation and investigate the accuracy of the distinction between the three grades. MATERIALS AND METHODS: After IRB approval, 340 cases were retrospectively selected from patients undergoing (18)FDG-PET/CT between 2007 and 2015 at our institution, with 85 cases in each grade and 85 controls with no active brown fat. Three readers evaluated all cases independently. Furthermore standardized uptake values (SUV) measurements were performed by two readers in a subset of 53 cases. Agreement between the readers was assessed with Cohen's Kappa (k), the concordance correlation coefficient (CCC) and the intraclass correlation coefficient (ICC). Accuracy was assessed with Bland-Altman and receiver operating characteristics (ROC) analysis. A Bonferroni-corrected two-tailed p<0.016 was considered statistically significant. RESULTS: Agreement for BAT grade was excellent by all three metrics with k=0.83-0.89, CCC=0.83-0.89 and ICC=0.91-0.94. Bland-Altman analysis revealed only slight average over- or underestimation (-0.01-0.14) with the majority of disagreements within one grade. ROC analysis yielded slightly less accurate classification between higher vs. lower grades (Area under the ROC curves 0.78-0.84 vs. 0.88-0.92) but no significant differences between readers. Agreement was also excellent for the maximum SUV and the total brown fat volume (k=0.90 and 0.94, CCC=0.93 and 0.99, ICC=0.96 and 0.99), but Bland-Altman plots revealed a tendency to underestimate activity by one of the readers. CONCLUSION: Grading the activation of brown fat by assessment of the most caudally activated depots results in excellent interreader agreement, comparable to SUV measurements.

Local resectability assessment of head and neck cancer: Positron emission tomography/MRI versus positron emission tomography/CT.

BACKGROUND: The purpose of this study was to compare the diagnostic accuracy of positron emission tomography (PET)/MRI with PET/CT for local resectability of head and neck cancer. METHODS: Sequential contrast-enhanced PET/CT-MRI was performed in 58 patients referred for the staging or restaging of head and neck cancer. Tumors were assessed with PET/CT and PET/MRI for the presence of resectability-defining factors: T4b status (mediastinal invasion, invasion of the prevertebral space, and vascular encasement), and another 8 findings that would imply obstacles for surgical cure (invasion of the laryngeal cartilage, invasion of the preepiglottic fat pad, perineural spread, orbital invasion, bone infiltration, skull base invasion, dural infiltration, and invasion of the brachial plexus). RESULTS: The sensitivity/specificity/accuracy of local resectability-defining factors of PET/CT and PET/MRI was 0.92/0.99/0.98 and 0.98/0.99/0.99 (P = .727), respectively, per lesion, and 0.96/0.87/0.91 and 0.96/0.90/0.93 (P = .687), respectively, per patient. CONCLUSION: Both contrast-enhanced PET/MRI and contrast-enhanced PET/CT can serve as reliable examinations for defining local resectability of head and neck cancer.

Complementary Prognostic Value of Pelvic Magnetic Resonance Imaging and Whole-Body Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Pretreatment Assessment of Patients With Cervical Cancer.

OBJECTIVE: The aim of this study was to evaluate the incremental prognostic value of pelvic magnetic resonance imaging (MRI) and whole-body F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) findings compared with clinical-histopathologic factors in patients with newly diagnosed cervical cancer. METHODS: The institutional review board approved this retrospective study of 114 patients (median age, 40.6 years) with International Federation of Gynecology and Obstetrics (FIGO) stage I-IVB cervical cancer who underwent pretreatment MRI and PET/CT. All scans were reviewed for locoregional tumor extent, pelvic or/and para-aortic lymphadenopathy, and distant metastases. Univariate Cox proportional hazard regression was performed to evaluate associations between clinical-histopathologic factors, imaging findings, and progression-free survival (PFS). Multivariate models were built using independent predictors for PFS. Harrell C was used to measure concordance (C index). RESULTS: Forty patients progressed within a median time of 10.4 months (range, 0.4-40.3 months). At univariate analysis, age, FIGO stage, tumor histology, tumor grade, and all MRI and PET/CT features were significantly associated with PFS (P < 0.0001 to P = 0.0474). A multivariate model including clinical and imaging parameters (parametrial invasion on MRI and para-aortic lymphadenopathy/distant metastases on PET/CT) had significantly higher concordance for predicting PFS than a model including clinical parameters only (C index: 0.81 [95% confidence interval, 0.75-0.87] vs 0.68 [95% confidence interval, 0.59-0.78]; P < 0.001). The comparison of C indices for the combined clinical and imaging model approached significance when compared with a FIGO stage model (C index: 0.81 [95% confidence interval, 0.75-0.87] vs 0.75 [95% confidence interval, 0.69-0.82]; P = 0.058). CONCLUSIONS: In patients with newly diagnosed cervical cancer, a prognostic model including combined MRI and PET/CT findings provides information that complements clinical and histopathologic factors.

Correlation between therapy response assessment using FDG PET/CT and histopathologic tumor regression grade in hepatic metastasis of colorectal carcinoma after neoadjuvant therapy.

PURPOSE: To evaluate the correlation between change in FDG uptake before and after chemotherapy in hepatic metastases of colorectal carcinoma (HCRC) and a histopathologic tumor regression grade (TRG). METHODS: In patients with HCRC, PET/CT data prior to hepatic surgery were retrospectively analyzed under an IRB waiver. The maximum standard uptake value (SUVmax) was measured before and after chemotherapy. The relative change of FDG activity in the identified lesions was calculated (dSUV). Histopathological specimens of resected metastases were graded on a 5-score TRG scale. A TRG of 1-3 was rated as a responding to therapy, whereas TRG 4-5 were regarded as non-responding lesions. RESULTS: 31 lesions were identified in 23 patients. Mean SUVmax before and after therapy was 6.9 ± 3.7 and 3.5 ± 1.8, respectively. The area under the receiver operator characteristic curve revealed a conclusive correlation between TRG and dSUV (AUC 0.773; 95% confidence interval 0.599-0.946) with a cut off at 41% decrease in FDG activity yielding a sensitivity and specificity of 72 and 75%, respectively. CONCLUSION: A relative change in FDG activity (dSUV) of more than 41% decrease correlated significantly with histopathological tumor regression and might be a prognostic tool for response to chemotherapy in HCRC.

Rapid cardiac hybrid imaging with minimized radiation dose for accurate non-invasive assessment of ischemic coronary artery disease.

BACKGROUND: Ischemic coronary artery disease (CAD) is a major cause for morbidity and mortality resulting in a continuously increasing number of diagnostic interventions. We have validated a new hybrid imaging method using minimized radiation dose for rapid non-invasive prediction of invasive coronary angiography (CA) findings with regard to coronary lesion detection and revascularization. METHODS: Forty patients referred for elective invasive coronary angiography (CA) due to suspected CAD were prospectively enrolled to undergo a low-dose CTCA with prospective ECG-triggering and a stress-only SPECT-MPI scan administering half of the standard low-dose stress (99m)Tc-tetrofosmin activity. The latter was acquired immediately after adenosine stress (omitting the standard 30-60 min waiting time). After fusing CTCA and SPECT-MPI decisions towards conservative management versus revascularization strategy based on hybrid images were compared to the decisions taken by the interventional operator in the catheterization laboratory based on CA. The latter served as standard of reference. RESULTS: Hybrid images yielded sensitivity, specificity, positive and negative predictive values and accuracy of 100%, 96.0%, 100%, 93.8% and 97.5% for predicting coronary revascularization. The estimated mean effective radiation doses were significantly lower for hybrid imaging (4.7 ± 1.0 mSv) than for invasive CA (8.7 ± 4.2 mSv; P<0.001 vs. hybrid). Total non-invasive protocol time was below 60 min, comparing favourably to standard SPECT protocols. CONCLUSIONS: Rapid cardiac hybrid imaging allows accurate prediction of invasive CA findings and of treatment decision despite minimized radiation dose and protocol time.

Non-invasive assessment of coronary artery disease with CT coronary angiography and SPECT: a novel dose-saving fast-track algorithm.

PURPOSE: To validate a new low-dose and rapid stepwise individualized algorithm for non-invasive assessment of ischemic coronary artery disease by sequential use of prospectively ECG-triggered low-dose CT coronary angiography (CTCA) and low-dose single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). METHODS: Forty patients referred for elective invasive coronary angiography (CA) were prospectively enrolled to undergo a comprehensive non-invasive evaluation with low-dose CTCA and a dose-reduced stress/rest SPECT-MPI scan (using dedicated reconstruction algorithms for low count scans). The following algorithm was reviewed: CTCA first, followed by a stress-only MPI if a coronary stenosis (> or = 50% diameter narrowing) or equivocal findings were observed. Only abnormal stress MPI scans were followed by rest MPI. The accuracy of the individualized algorithm to predict coronary revascularization and its mean effective radiation dose were assessed. RESULTS: CTCA documented CAD in 18 and equivocal findings in two patients, thus, requiring additional stress MPI scans. Of these, 16 were abnormal, therefore requiring a rest MPI scan, revealing ischemia in 15 patients. Sensitivity, specificity, negative and positive predictive value, and accuracy of the individualized algorithm for predicting coronary revascularization was 93.3%, 96.0%, 96.0%, 93.3% and 95.0% on a per-patient base. The mean effective radiation dose was significantly lower for the individualized (4.8 +/- 3.4 mSv) versus the comprehensive method (8.1 +/- 1.5 mSv) resulting in a total population radiation dose reduction of 132.6 mSv. CONCLUSION: This new individualized low-dose algorithm allows rapid and accurate prediction of invasive CA findings and of treatment decision with minimized radiation dose.