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Background/objectives: Accurate and uniform interpretation and reporting of metastatic prostate cancer (PCa) lesions on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) are indispensable. 18F-PSMA-1007 is increasingly used because of its favorable imaging characteristics. However, increased non-specific skeletal uptake may be an important pitfall of this radioligand. Therefore, we aimed to assess the interobserver variation in reporting skeletal 18F-PSMA-1007 uptake on PET/CT. Design/methods: In total, 33 18F-PSMA-1007 PET/CT scans of 21 patients with primary PCa and 12 patients with biochemical recurrence were included, and a total of 85 skeletal lesions were evaluated by three independent observers. The primary endpoint was the interobserver variability of the likelihood of malignancy of the skeletal lesions on both patient and lesion level (kappa analysis). Results: Observers qualified most lesions as not malignant (81–91%) and the overall mean interobserver agreement was moderate on both patient (κ: 0.54) and lesion level (κ: 0.55). In 52 lesions without corresponding CT substrate, the rating resulted in not malignant in 95–100%. Availability of additional imaging (60% of lesions) did not improve interobserver agreement (κ: 0.39 on lesion level) and resulted in unchanged rating for all observers in 78%. Conclusion: This interobserver analysis of skeletal 18F-PSMA-1007 uptake resulted in moderate agreement, in line with rates reported in literature. Importantly, the presence of non-specific skeletal uptake without CT substrate, as a potential shortcoming of 18F-PSMA-1007, did not impair interobserver agreement. [ABSTRACT FROM AUTHOR]

The gastrin-releasing peptide receptor (GRPr) is overexpressed in prostate cancer (PCa) cells, making it an excellent tool for targeted imaging. The 68 Ga-labeled GRPr antagonist SB3 has shown excellent results in preclinical and clinical studies and was selected for further clinical investigation. The aims of this phase I study were to investigate 68 Ga-SB3 PET/CT imaging of primary PCa tumors and assess safety. More aims included an investigation of biodistribution and dosimetry and a comparison with pathology and GRPr expression. Methods: Ten therapy-naïve, biopsy-confirmed PCa patients planned for prostatectomy were included. A 3-h extensive PET/CT imaging protocol was performed within 2 wk before prostatectomy. Prostate tissue was evaluated for tumor localization and Gleason score, and in vitro autoradiography was performed to determine GRPr expression. Available MRI scans performed within 3 mo before the study were matched. For dosimetry, residence times were estimated and effective dose to the body as well as absorbed doses to organs were calculated using the IDAC dose model, version 2.1. Results: Administration of 68 Ga-SB3 (187.4 ± 40.0 MBq, 40 ± 5 μg) was well tolerated; no significant changes in vital signs or laboratory results were observed. 68 Ga-SB3 PET/CT showed lesions in 8 of 10 patients. Pathologic analysis revealed a total of 16 tumor lesions, of which PET/CT showed 14, resulting in a sensitivity of 88%. 68 Ga-SB3 PET/CT imaging showed uptake in 2 large prostatic intraepithelial neoplasia foci, considered a precursor to PCa, resulting in an 88% specificity. Autoradiography of tumor lesions revealed heterogeneous GRPr expression and was negative in 4 patients. Both PET/CT-negative patients had a GRPr-negative tumor. In autoradiography-positive tumors, the level of GRPr expression showed a significant correlation to tracer uptake on PET/CT. Dosimetry calculations estimated the effective dose to be 0.0144 mSv/MBq, similar to other 68 Ga-labeled radiopeptides. The highest absorbed dose was detected in the physiologic GRPr-expressing pancreas (0.198 mGy/MBq), followed by the bladder wall and kidneys. Conclusion: 68 Ga-SB3 PET/CT is a safe imaging method and a promising tool for early PCa imaging., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Aims: Hybrid single photon emission computed tomography (SPECT)/coronary computed tomography angiography (CCTA) has only been evaluated for its diagnostic accuracy as a single test in patients suspected of significant coronary artery disease (CAD). Added value of hybrid SPECT/CCTA beyond usual clinical work-up, or use of each of these tests separately, remains unclear. We evaluated the added value of hybrid myocardial perfusion SPECT (SPECT) and CCTA, beyond pre-test likelihood and exercise stress ECG (X-ECG), in the diagnosis of CAD., Methods and Results: Two hundred and five patients with stable angina pectoris and intermediate-to-high pre-test likelihood were prospectively included. All patients underwent clinical history and examination, X-ECG, stress and rest SPECT, coronary calcium scoring (CCS) and CCTA. Fractional flow reserve measurement <0.80 or a lesion >50% on coronary angiography (CA) served as reference standard for significant CAD. Multiple imputation was used to correct for missing test results (17-20%). Added value of hybrid SPECT/CCTA to the basic model of pre-test likelihood plus X-ECG was quantified using logistic regression analysis. Model differences were then assessed using differences in C-index and in net reclassification improvement (NRI). The basic model had a C-index of 0.73 (95%CI 0.66-0.80). This significantly increased to 0.85 (95%CI 0.80-0.91) by addition of only SPECT, to 0.90 (95%CI 0.85-0.94) when adding only CCTA, and to 0.96 (95%CI 0.92-0.99) when adding hybrid SPECT/CCTA. The accompanying NRIs were 0.82 (95%CI 0.62-1.02), 0.86 (95%CI 0.66-1.06) and 1.57 (95%CI 1.11-1.59) respectively., Conclusion: Current analysis resembles clinical routine of layered testing and shows that hybrid SPECT/CCTA imaging has a substantially higher yield than standalone SPECT or CCTA in the diagnostic workup of patients suspected of significant CAD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: Hybrid myocardial perfusion imaging with single photon emission computed tomography (SPECT) and CT coronary angiography (CCTA) has the potential to play a major role in patients with non-conclusive SPECT or CCTA results. We evaluated the performance of hybrid SPECT/CCTA vs. standalone SPECT and CCTA for the diagnosis of significant coronary artery disease (CAD) in patients with an intermediate to high pre-test likelihood of CAD., Methods and Results: In total, 98 patients (mean age 62.5 ± 10.1 years, 68.4% male) with stable anginal complaints and a median pre-test likelihood of 87% (range 22-95%) were prospectively included in this study. Hybrid SPECT/CCTA was performed prior to conventional coronary angiography (CA) including fractional flow reserve (FFR) measurements. Hybrid analysis was performed by combined interpretation of SPECT and CCTA images. The sensitivity, specificity, positive (PPV), and negative (NPV) predictive values were calculated for standalone SPECT, CCTA, and hybrid SPECT/CCTA on per patient level, using an FFR <0.80 as a reference for significant CAD. Significant CAD was demonstrated in 56 patients (57.9%). Non-conclusive SPECT or CCTA results were found in 32 (32.7%) patients. SPECT had a sensitivity of 93%, specificity 79%, PPV 85%, and NPV 89%. CCTA had a sensitivity of 98%, specificity 62%, PPV 77%, and NPV 96%. Hybrid analysis of SPECT and CCTA improved the overall performance: sensitivity, specificity, PPV, and NPV for the presence of significant CAD to 96, 95, 96, and 95%, respectively., Conclusions: In > 40% of the patients with a high pre-test likelihood no significant CAD was demonstrated, emphasizing the value of accurate pre-treatment cardiovascular imaging. Hybrid SPECT/CCTA was able to accurately diagnose and exclude significant CAD surpassing standalone myocardial SPECT and CCTA, vs. a reference standard of FFR measurements.