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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]

Information is scarce on the effects of right ventricular apical (RVA) pacing on regional and global myocardial blood flow (MBF). The purpose of this study was to assess the relationship between pacing rate and both regional and global MBF. Four patients with exclusive atrial pacing and six patients with exclusive RVA pacing underwent three consecutive HO positron emission tomography scans at 60, 90, and 130 pulses per minute (ppm). For each pacing rate, regional and global MBF was determined. In all patients, the left ventricular (LV) function was normal. By varying the atrial pacing rate from 60 to 130 ppm, the mean global MBF increased from 0.94 to 1.40 mL/g/min, whereas the mean septal to lateral MBF ratio decreased from 1.09 to 0.83. In ventricular-paced patients at corresponding rates, the mean global MBF also increased from 1.07 to 1.52 mL/g/min but here the mean septal to lateral MBF ratio increased from 0.83 to 1.0. During both acute atrial and RVA pacing, regional and global MBF increases with higher pacing rates. However, the septal to lateral MBF ratio decreases with atrial pacing and increases with RVA pacing in patients with normal LV function. In RVA pacing, these different rate-dependent effects on regional MBF can be considered as a favorable factor that helps to understand why in some long-term paced patients, LV function is preserved. (PACE 2011; 34:587-592) [ABSTRACT FROM AUTHOR]

The value of myocardial perfusion SPECT (MPS) for patients with left bundle branch block (LBBB) or right ventricular apical (RVA) pacing seems reduced. The prognosis of patients with only abnormal activation related perfusion defects (AARD) due to LBBB or RVA-pacing is similar to those with a normal MPS. We assessed the prognostic value of MPS in patients with LBBB or RVA pacing. Patients with LBBB or RVA pacing referred for vasodilator stress MPS between April 2002 and January 2006 were analyzed. Group 1 are patients with normal MPS and MPS with AARD. Group 2 are patients with an MPS with a perfusion defect extending outside the AARD area. Events were cardiac death, acute myocardial infarction and coronary revascularization. In Group 1 (101 patients) 12 events and in Group 2 (96 patients) 45 events occurred during a mean follow-up of 2.6 ± 1.5 years. The prognosis of Group 2 was significantly worse (49%) compared with Group 1 (91%). The annual cardiac death rate was 0.7%/year in Group 1 and 6.4%/year in Group 2 ( P < .001). The prognosis of patients with LBBB was not different from those with RVA pacing. Group 2 had a significantly worse cardiac prognosis compared to Group 1. The annual cardiac death rate of <1% in Group 1 warrants a watchful waiting strategy, whereas the cardiac death rate in Group 2 warrants aggressive invasive coronary strategies. [ABSTRACT FROM AUTHOR]

Background: To define the physical and clinical reproducibility of Tl myocardial perfusion SPECT (MPS), this study assesses the variation between two repeated rest Tl MPS with repositioning only, with a two-hour time interval and with phantom measurements as a reference. Methods: Three anthropomorphic thorax phantoms were filled with Tl. For each phantom five repeated Tl MPS were obtained. In addition, in 20 patients repeated Tl rest-MPS and in 26 patients early and delayed Tl rest-MPS were performed. Quantitative analysis was done using MunichHeart. Statistical methods were used to calculate variability. Visual analysis was performed by 2 independent observers. Results: The average variation between repeated phantom MPS was 0.5% (95% confidence interval (CI): −0.4% to 1.4%). For patient scans this was −5.0% (95% CI: −2.5% to −7.5%) and between early and delayed Tl MPS −15.5% (95% CI: −11.7% to −19.3%). Visual assessment revealed no clinical significant differences between rest Tl and repeated or delayed Tl MPS. Conclusions: Repositioning in phantom Tl MPS does not cause significant variation. Repeated Tl MPS in patients shows 5.0% decrease of Tl in 30 minutes, which increases to 15% during a two-hour time interval without quantitative or visual regional differences. This decrease indicates a time-related washout of Tl, but does not change clinical diagnosis. [ABSTRACT FROM AUTHOR]

Aims: A depressed left ventricular function (LVF) is sometimes observed during right ventricular apical (RVA) pacing, but any prediction of this adverse effect cannot be done. Right ventricular outflow tract (RVOT) pacing is thought to deteriorate LVF less frequently because of a more normal LV activation pattern. This study aims to assess the acute effects of RVA and RVOT pacing on LVF in order to determine the contribution of echocardiography for the selection of the optimum pacing site during pacemaker (PM) implantation. [ABSTRACT FROM PUBLISHER]

The incremental prognostic value of dual-isotope myocardial perfusion scintigraphy using technetium-99m tetrofosmin for the stress images was evaluated in 597 consecutive patients with known or suspected coronary artery disease. We used semi-quantitative visual analysis with a five-point scoring system and calculated the summed stress score, the summed rest score and the summed difference score. During the 2-year follow-up period, 46 'hard' cardiac events occurred: 16 cardiac deaths and 30 non-fatal myocardial infarctions. Kaplan-Meier analysis demonstrated a favourable prognosis for patients with normal scans as compared with patients with mildly to moderately or severely abnormal scans (P<0.001). Multivariate analysis demonstrated incremental prognostic in-formation for nuclear variables. A very low rate of hard cardiac events was observed in patients with a low summed stress score. Thus, nuclear variables provide incremental prognostic information and could be used to guide the management process with respect to whether or not to proceed with further invasive procedures. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Hybrid myocardial perfusion SPECT/CT coronary angiography and invasive coronary angiography in patients with stable angina pectoris lead to similar treatment decision" that was published in the previous issue.

Purpose: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan is the standard imaging procedure for biochemical recurrent prostate cancer postprostatectomy because of its high detection rate at low serum prostate-specific antigen levels. However, existing guidelines for clinical target volume (CTV) in prostate bed salvage external beam radiation therapy (sEBRT) are primarily based on experience-based clinical consensus and have been validated using conventional imaging modalities. Therefore, this study aimed to optimize CTV definition in sEBRT by using PSMA PET/CT-detected local recurrences (LRs)., Methods and Materials: Patients with suspected LR on PSMA PET/CT postprostatectomy were retrospectively enrolled in 9 Dutch centers. Anonymized scans were centrally reviewed by an expert nuclear medicine physician. Each boundary of the CTV guideline from the Groupe Francophone de Radiothérapie en Urologie (GFRU) was evaluated and adapted to improve the accuracy and coverage of the area at risk of LR (CTV) on PSMA PET/CT. The proposed CTV adaptation was discussed with the radiation oncologists of the participating centers, and final consensus was reached. To assess reproducibility, the participating centers were asked to delineate 3 new cases according to the new PERYTON-CTV, and the submitted contours were evaluated using the Dice similarity coefficient (DSC)., Results: After central review, 93 LRs were identified on 83 PSMA PET/CTs. The proposed CTV definition improved the coverage of PSMA PET/CT-detected LRs from 67% to 96% compared with the GFRU-CTV, while reducing the GFRU-CTV by 25%. The new CTV was highly reproducible, with a mean DSC of 0.82 (range, 0.81-0.83)., Conclusions: This study contributes to the optimization of CTV definition in postprostatectomy sEBRT by using the pattern of LR detected on PSMA PET/CT. The PERYTON-CTV is highly reproducible across the participating centers and ensures coverage of 96% LRs while reducing the GFRU-CTV by 25%., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The PERYTON trial is a multicenter randomized controlled trial that will investigate whether the treatment outcome of salvage external beam radiation therapy (sEBRT) will be improved with hypofractionated radiation therapy. A pretrial quality assurance (QA) program was undertaken to ensure protocol compliance within the PERYTON trial and to assess variation in sEBRT treatment protocols between the participating centers., Methods and Materials: Completion of the QA program was mandatory for each participating center (N = 8) to start patient inclusion. The pretrial QA program included (1) a questionnaire on the center-specific sEBRT protocol, (2) a delineation exercise of the clinical target volume (CTV) and organs at risk, and (3) a treatment planning exercise. All contours were analyzed using the pairwise dice similarity coefficient (DSC) and the 50th and 95th percentile Hausdorff distance (HD50 and HD95, respectively). The submitted treatment plans were reviewed for protocol compliance., Results: The results of the questionnaire showed that high-quality, state-of-the-art radiation therapy techniques were used in the participating centers and identified variations of the sEBRT protocols used concerning the position verification and preparation techniques. The submitted CTVs showed significant variation, with a range in volume of 29 cm 3 to 167 cm 3 , a mean pairwise DSC of 0.52, and a mean HD50 and HD95 of 2.3 mm and 24.4 mm, respectively. Only in 1 center the treatment plan required adaptation before meeting all constraints of the PERYTON protocol., Conclusions: The pretrial QA of the PERYTON trial demonstrated that high-quality, but variable, radiation techniques were used in the 8 participating centers. The treatment planning exercise confirmed that the dose constraints of the PERYTON protocol were feasible for all participating centers. The observed variation in CTV delineation led to agreement on a new (image-based) delineation guideline to be used by all participating centers within the PERYTON trial., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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.)

Purpose: [ 177 Lu]Lu-PSMA-617 radioligand therapy ( 177 Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of 177 Lu-PSMA in pateints with low-volume mHSPC., Patients and Methods: Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [ 68 Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of 177 Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS., Results: All patients received two cycles of 177 Lu-PSMA without complications. No treatment-related grade III-IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease., Conclusions: 177 Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC., (©2021 American Association for Cancer Research.)

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.

A patient with chronic myelomonocytic leukemia developed drug-induced pulmonary toxicity after using low dose oral etoposide. Because etoposide-induced pulmonary toxicity is an uncommon but serious adverse event, clinicians must be vigilant about the possibility of it, so that the optimal treatment can start as soon as possible. This report demonstrates that PET scintigraphy might be a helpful tool in the early diagnosis of drug-induced pulmonary toxicity.

The incremental prognostic value of dual-isotope myocardial perfusion scintigraphy using technetium-99m tetrofosmin for the stress images was evaluated in 597 consecutive patients with known or suspected coronary artery disease. We used semi-quantitative visual analysis with a five-point scoring system and calculated the summed stress score, the summed rest score and the summed difference score. During the 2-year follow-up period, 46 "hard" cardiac events occurred: 16 cardiac deaths and 30 non-fatal myocardial infarctions. Kaplan-Meier analysis demonstrated a favourable prognosis for patients with normal scans as compared with patients with mildly to moderately or severely abnormal scans ( P<0.001). Multivariate analysis demonstrated incremental prognostic information for nuclear variables. A very low rate of hard cardiac events was observed in patients with a low summed stress score. Thus, nuclear variables provide incremental prognostic information and could be used to guide the management process with respect to whether or not to proceed with further invasive procedures.