Diagnostic accuracy and clinical value of [68Ga]Ga-FAPI-46 PET/CT for staging patients with ovarian cancer: study protocol for a prospective clinical trial.

BACKGROUND: [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [18F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [18F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT and [18F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management. METHODS AND DESIGN: Fifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [18F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [68Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [18F]FDG PET/CT). Study subjects in Group B will undergo an additional [68Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [68Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting. DISCUSSION: To our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [68Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [68Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response. TRIAL REGISTRATION: clinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.

Designing clinical trials based on modern imaging and metastasis-directed treatments in patients with oligometastatic breast cancer: a consensus recommendation from the EORTC Imaging and Breast Cancer Groups.

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed.

The diagnostic accuracy of radiolabeled PSMA-ligand PET for tumour staging in newly diagnosed prostate cancer patients compared to histopathology: a systematic review and meta-analysis.

PURPOSE: The current clinical recommendations posit the deployment of specific approved radiolabeled prostate-specific membrane antigen-ligand positron emission tomography (PSMA PET) for detecting metastatic prostate cancer during primary staging. Nevertheless, the precise efficacy of such ligands in localizing intraprostatic tumours (index tumour) and T-staging is not well established. Consequently, the objective of this inquiry is to ascertain the diagnostic accuracy of PSMA-PET in the tumour staging of newly diagnosed prostate cancer by means of a meta-analysis that integrates studies utilizing histological confirmation as the reference standard. METHODS: In this study, we conducted a systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases using a predefined collection of search terms. These terms included 'PSMA PET', 'primary staging', and 'prostate cancer'. Subsequently, two independent reviewers evaluated all the studies based on predetermined inclusion criteria, extracted pertinent data, and assessed the quality of evidence. Any disparities were resolved by a third reviewer. A random effects Sidik-Jonkman model was applied to conduct a meta-analysis and estimate the diagnostic accuracy on a per-patient basis, along with 95% confidence intervals. Moreover, an appraisal regarding the likelihood of publication bias and the impact of small-study effects was performed utilizing both Egger's test and a graphical examination of the funnel plot. RESULTS: The present analysis comprised a total of twenty-three scientific papers encompassing 969 patients and involved their analysis by both qualitative and quantitative approaches. The results of this study demonstrated that the estimated diagnostic accuracy of PSMA PET/CT and PSMA PET/MRI, for the detection of intraprostatic tumours, regardless of the type of PSMA-ligand, was 86% (95% CI: 76-96%) and 97% (95% CI: 94-100%), respectively. Furthermore, the diagnostic accuracy for the detection of extraprostatic extension (EPE) was 73% (95% CI: 64-82%) and 77% (95% CI: 69-85%), while the diagnostic accuracy for the detection of seminal vesicle involvement (SVI) was 87% (95% CI: 80-93) and 90% (95% CI: 82-99%), respectively. CONCLUSION: The present investigation has demonstrated that PSMA PET/MRI surpasses currently recommended multiparametric magnetic resonance imaging (mpMRI) in terms of diagnostic accuracy as inferred from a notable data trajectory, whereas PSMA-PET/CT exhibited comparable diagnostic accuracy for intraprostatic tumour detection and T-staging compared to mpMRI. Nevertheless, the analysis has identified certain potential limitations, such as small-study effects and a potential for publication bias, which may impact the overall conclusions drawn from this study.

Clinical significance of atypical 68Ga-DOTATOC prostatic uptake on PET/CT: A ten-year review.

OBJECTIVE: Gallium-68-DOTA-D-Phe1-Try3-Octreotide (68Ga-DOTATOC) is a radiolabeled somatostatin receptor (SSTR) analog that is widely used in the imaging of neuroendocrine tumors (NET). Benign and malignant prostate tumors have been observed to express SSTR. Diffuse symmetric DOTATOC uptake in the prostate is a normal positron emission tomography (PET) finding. The aim of this study was to evaluate the frequency and clinical significance of incidental atypical prostatic uptake in men undergoing 68Ga-DOTATOC PET/computed tomography(CT). SUBJECTS AND METHODS: A retrospective review of consecutive male patients who underwent 68Ga-DOTATOC PET/CT studies at Aalborg University Hospital, Denmark, from November 2010 to April 2020 was performed. Positron emission tomography/CT reports were searched for text words or phrases indicating incidental atypical prostatic uptake. In the resulting cohort, PET/CT were re-evaluated, and DOTATOC uptake in the prostate gland was categorized as focal, diffuse or mixed. The intensity of the uptake was visually graded using the Krenning visual score. Follow-up was based on all available clinical, biochemical, imaging, and pathology follow-up. RESULTS: A total of 178 male patients underwent 193 68Ga-DOTATOC PET/CT scans. Incidental atypical uptake of 68Ga-DOTATOC on PET/CT in the prostatic bed was observed in eight patients (4.5%) (mean age 67 years, range 58-85 years). Six patients (75%) had diffuse uptake; two (25%) patients had focal uptake. Four patients out of eight with incidental findings (50%) had uptake less than or equal to that of the liver (Krenning score 2); four patients (50%) had uptake greater than that of the liver (score 3). All patients had measurements of serum prostate-specific antigen and were referred for urological evaluation. Five patients (62%) underwent a transrectal ultrasound, and three required a biopsy of the prostate. No cases of prostate malignancy (including prostatic cancer) were diagnosed. CONCLUSION: During a 10-year period, we found that 4.5% of men exhibited prostate incidentalomas on 68Ga-DOTATOC PET/CT. No malignancy was found in the prostate in this population. Our data indicate absent malignancy among incidental 68Ga-DOTATOC findings in the prostate.

Indeterminate thyroid cytology in an iodine-deficient population: Prevalence, operation rate, risk of malignancy anddiagnostic value of thyroid scintigraphy and 18F-FDG PET imaging parameters.

OBJECTIVE: Patients with indeterminate thyroid cytology often have a diagnostic hemithyroidectomy. The role of molecular imaging, particularly fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), is controversial, and demographic variations in tumor prevalence and histology influence test performance and clinical utility. We retrospectively assessed the prevalence of indeterminate thyroid cytology and the malignancy rate in patients from an iodine deficient area, and evaluated the diagnostic value of preoperative thyroid scintigraphy and 18F-FDG PET/CT among operated patients. SUBJECTS AND METHODS: From 2006-2018, all patients with indeterminate thyroid cytology from the North Denmark region were included in the study (population 600,000).Clinical data, including operation rate, preoperative molecular imaging, and histopathological diagnosis, were retrieved. The results from preoperative thyroid scintigraphy and 18F-FDG PET/CT-scanning were compared to the final histopathological diagnosis. RESULTS: Four hundred and thirty-three patients were found with indeterminate thyroid cytology.The main registered reasons for conducting a fine needle aspiration biopsy (FNAB) were "cold nodule", goiter or a palpable nodule (n=312). In 40 patients (9%), FNAB was registered as conducted due to a PET incidentaloma. Four hundred and two patients (93%) underwent diagnostic lobectomy, and this population formed the study population for the following explorative study: One-hundred and two patients (25%) had a malignant diagnosis. In 226 (56%) and 51 (25%) patients, respectively, preoperative thyroid scintigraphy and 18F-FDG PET/computed tomography (CT) was performed. Among patients with a final malignant disease who had a thyroid scintigraphy (40 patients), a cold nodule was seen in 90% of cases; one (atypical) patient presented a warm nodule. Among patients with a final malignant disease 16 patients (16%) had a 18F-FDG PET (incl. 3 missing PET scans). Among the 51 patients with preoperative 18F-FDG PET/CT, no difference in the PET-derived parameters was found between benign (n=33) and malignant tumors (n=13). CONCLUSION: The prevalence of malignancy (25%) was comparable with that in other studies. In patients with a preoperative thyroid scintigraphy, 90% of malignant cases had a cold nodule on scintigraphy. In patients with a preoperative PET/CT-scanning presenting focal 18F-FDG-uptake, PET-derived parameters had no diagnostic value. However, the diagnostic value of 18F-FDG-avidity vs. non-avidity needs to be addressed prospectively.

Comparing the clinical performance and cost efficacy of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in the diagnosis of recurrent prostate cancer: a Markov chain decision analysis.

PURPOSE: Amongst others, [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 are available for the detection of recurrent prostate cancer (rPC). There are currently limited data comparing the performance of these two radioligands with respect to clinical outcomes or their cost efficacy, which this study aims to address. METHODS: Two hundred and forty-four patients undergoing PSMA PET/CT for rPC were retrospectively analysed for this study (one hundred and twenty two with each radiopharmaceutical) to generate rates of PET positivity, negativity and unclear findings. Patients underwent follow-up to determine the rate of additional examinations and to confirm PET findings. A Markov chain decision analysis was implemented to model clinical decision-making processes and to analyse clinical performance of the two tracers. We determine their clinical cost efficacies using cost data from several countries where both radiotracers are in routine use. RESULTS: The PET positivity rate was non-significantly higher for [18F]PSMA-1007 compared to [68Ga]Ga-PSMA-11 (91.8% vs. 86.9%, p = 0.68), whereas the rate of uncertain findings was significantly greater (17.2% vs. 8.25%, p = 0.02). The probability of a true positive finding was higher for [68Ga]Ga-PSMA-11 (0.90, 95% CI 0.70-0.98) vs. [18F]PSMA-1007 (0.81, 95% CI 0.66-0.91). A significantly (p < 0.0001) higher PPV for [68Ga]Ga-PSMA-11 (0.99, 95% CI 0.99-1.0 vs. 0.86) was found compared to [18F]PSMA-1007 (0.86, 95% CI 0.82-1.00). Intervention efficacy analysis favoured [68Ga]Ga-PSMA-11, where the number needed to image (to achieve a true positive finding) was 10.58 and the number needed to image to harm (to achieve a false positive finding) was - 8.08. A cost efficacy analysis favours [68Ga]Ga-PSMA-11 in three of the four jurisdictions analysed where health economic data was available (Switzerland, Israel, Australia) and [18F]PSMA-1007 in one jurisdiction (Denmark). CONCLUSION: The analysis reveals a non-significantly higher PET positivity rate for [18F]PSMA-1007, but finds significantly greater rates of uncertain findings and false positive findings when compared to [68Ga]Ga-PSMA-11. We find differences in the two tracers in terms of clinical performance and cost efficacy. The method presented herein is generalisable and can be used with clinical or cost data for other countries or tracers.

Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis.

PURPOSE: Many radiotracers are currently available for the detection of recurrent prostate cancer (rPC), yet many have not been compared head-to-head in comparative imaging studies. There is therefore an unmet need for evidence synthesis to guide evidence-based decisions in the selection of radiotracers. The objective of this study was therefore to assess the detection rate of various radiotracers for the rPC. METHODS: The PUBMED, EMBASE, and the EU and NIH trials databases were searched without date or language restriction for comparative imaging tracers for 13 radiotracers of principal interest. Key search terms included 18F-PSMA-1007, 18F-DCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18F-Fluciclovine, 18F-FABC, 18F-Choline, 11C-Choline, and 68Ga-RM2. Studies reporting comparative imaging data in humans in rPC were selected. Single armed studies and matched pair analyses were excluded. Twelve studies with eight radiotracers were eligible for inclusion. Two independent reviewers screened all studies (using the PRISMA-NMA statement) for inclusion criteria, extracted data, and assessed risk of bias (using the QUADAS-2 tool). A network meta-analysis was performed using Markov-Chain Monte Carlo Bayesian analysis to obtain estimated detection rate odds ratios for each tracer combination. RESULTS: A majority of studies were judged to be at risk of publication bias. With the exception of 18F-PSMA-1007, little difference in terms of detection rate was revealed between the three most commonly used PSMA-radiotracers (68Ga-PSMA-11, 18F-PSMA-1007, 18F-DCFPyl), which in turn showed clear superiority to choline and fluciclovine using the derived network. CONCLUSION: Differences in patient-level detection rates were observed between PSMA- and choline-radiotracers. However, there is currently insufficient evidence to favour one of the four routinely used PSMA-radioligands (PSMA-11, PSMA-1007, PSMA-I&T, and DCFPyl) over another owing to the limited evidence base and risk of publication bias revealed by our systematic review. A further limitation was lack of reporting on diagnostic accuracy, which might favour radiotracers with low specificity in an analysis restricted only to detection rate. The NMA derived can be used to inform the design of future clinical trials and highlight areas where current evidence is weak.

Response evaluation of bone metastasis in prostate cancer: Preliminary comparison of computerized bone scan index versus standardized clinical criteria.

OBJECTIVE: The correlation between the computer-assisted bone scan index (BSI) responses versus clinical response classification if bone metastases in prostate cancer patients are not clear. We compared changes in BSI with Prostate Cancer Working Group-3 (PCWG3) and MD Anderson (MDA) criteria. MATERIALS AND METHODS: Fifty-six consecutive patients with at least two bone scans (BS) within 12 months were included, who had BS before and after treatment with the same anticancer agent. RESULTS: Progressive disease (PD) by PCWG3 criteria was seen in 28% of the cases (median BSI increased by 1.69 units) versus non-PD in 72% (BSI change -0.13). MDAnderson showed PD in 34% (BSI increase 0.49), 45% stable disease (BSI change 0.00), and 20% partial responses (BSI decrease 1.44). Absolute BSI changes differed significantly among response categories by PCWG3 and MDA criteria (both P<0.0001). Response classification using dichotomized BSI data (>0/≤0 and >0.3/≤0.3 BSI units) showed a significant correlation with PCWG3 and MDA criteria (all P<0.001). Absolute BSI changes and dichotomized BSI correlated to prostate-specific antigen responses (both P<0.001) but not to clinical responses. CONCLUSION: Absolute changes in BSI and BSI response classification correlated significantly with standardized clinical response criteria for the assessment of treatment responses of skeletal metastases in prostate cancer.

68Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer-a modified protocol compared with the common protocol.

PURPOSE: 68Ga-PSMA-11 PET/CT is commonly performed at 1 h post injection (p.i.). However, various publications have demonstrated that most prostate cancer (PC) lesions exhibit higher contrast at later imaging. The aim of this study was to compare the "common" protocol of 68Ga-PSMA-11 PET/CT with a modified protocol. METHODS: In 2017, we used the following scanning protocol for 68Ga-PSMA-11 PET/CT in patients with recurrent PC: acquisition at 1 h p.i. without further preparations. From 2018, all scans were conducted at 1.5 h p.i. In addition, patients were orally hydrated with 1 L of water 0.5 h p.i. and were injected with 20 mg of furosemide 1 h p.i. Both protocols including 112 patients (2017) and 156 (modified protocol in 2018) were retrospectively compared. Rates of pathologic scans, maximum standardized uptake values (SUVmax), and tumor contrast (ratio lesion-SUVmax/background-SUVmean) as well as average standardized uptake values (SUVmean) of urinary bladder were analyzed. RESULTS: Both tumor contrast and tracer uptake were significantly (p < 0.001) higher in the novel protocol. Although statistically not significant, the rates of pathologic scans were also higher in the modified protocol: 76.3% vs. 68.8% for all PSA values including 38.9% vs. 25.0% for PSA < 0.5 ng/ml and 60.0% vs. 56.7% for PSA > 0.5-≤ 2.0 ng/ml. Average SUVmean of the urinary bladder was significantly (p < 0.001) lower with the modified protocol. CONCLUSIONS: The modified protocol, which includes a combination of delayed image acquisition at 1.5 h p.i., hydration, and furosemide resulted in higher tumor contrast and seems to have the potential to increase the rates of pathological scans, especially at low PSA levels.

68Ga-PSMA PET/CT compared with MRI/CT and diffusion-weighted MRI for primary lymph node staging prior to definitive radiotherapy in prostate cancer: a prospective diagnostic test accuracy study.

BACKGROUND: The aim was to compare the diagnostic accuracy of 68Ga-PSMA PET/CT with conventional cross-sectional imaging and diffusion-weighted MRI (DW-MRI) for detecting lymph node metastasis (LNM) to stage prostate cancer patients. Twenty consecutive, newly- diagnosed prostate cancer patients were prospectively enrolled and underwent 68Ga-PSMA-11 PET/CT, anatomical MRI or contrast-enhanced CT, and DW-MRI prior to laparoscopic, template-based, extended lymph node dissection. Histopathological findings served as the reference test. RESULTS: Histopathology showed LNM in 13 of 20 patients (19 high-risk, 1 intermediate risk). Five patients had metastasis-suspected lymph nodes on 68Ga-PSMA PET/CT. Patient-based analysis showed that the sensitivity and specificity for detecting LNM were 39% and 100% with 68Ga-PSMA PET/CT, 8% and 100% with MRI/CT, and 36% and 83% with DW-MRI, respectively. The positive and negative predictive values were 100% and 49% with 68Ga-PSMA PET/C, 100% and 37% with MRI/CT, and 80% and 42% with DW-MRI. Of 573 dissected lymph nodes, 33 were LNM from 26 regions. True-positive LNM on 68Ga-PSMA PET/CT was 9-11 mm in diameter, whereas false-negative LNM had a median diameter of 4 mm, with only 3 of 30 lymph nodes being larger than 10 mm. LNM were positive for PSMA by immunostaining. CONCLUSIONS: The sensitivity of 68Ga-PSMA PET/CT was notably better than that of MRI/CT and comparable to that of DW-MRI. Some false positive findings with DW-MRI reduced its specificity and positive predictive value compared with those of 68Ga-PSMA PET/CT and MRI/CT.

The Ability of the Toe-Brachial Index to Predict the Outcome of Treadmill Exercise Testing in Patients with a Normal Resting Ankle-Brachial Index.

BACKGROUND: Peripheral arterial disease (PAD) in the presence of a normal ankle-brachial index (ABI) can be diagnosed noninvasively by measuring a postexercise ABI or by measuring the toe-brachial index (TBI). METHODS: This was a prospective comparative study. Over a period of 30 months, a total of 415 patients who were referred with the suspicion of vascular claudication and resting values of 0.91 ≤ ABI<1.40 were further evaluated for the resting TBI and postexercise ABI by treadmill testing. RESULTS: A total of 325 (39%) of the 830 investigated limbs had a low TBI (≤0.70), and 505 (61%) had a normal TBI. Of the limbs with a low TBI, 160 (49%) had PAD according to a postexercise ABI versus 165 (33%) of the limbs with normal TBI. The overall agreement in PAD classification between the two methods was 500/830 (60%) with a Cohen's kappa = 0.166 (95% CI: 0.096-0.232). The data showed an inverse correlation between the magnitude of the TBI decrease, as well as the resting ABI, and the probability of an abnormal postexercise ABI. On average, limbs with a low TBI had a lower resting ABI than patients with a normal TBI (1.07 ± 0.09 vs. 1.13 ± 0.10, P < 0.001). The groups with a low TBI had a significantly higher ratio of abnormal test results than patients with a normal TBI, in limbs with ABI (0.96-1.00) and ABI >1.10 (P ≤ 0.022 for both), but there were no statistically significant differences found in other ABI intervals (P > 0.200 for all). CONCLUSIONS: The magnitude of the TBI reduction correlates with an increased probability of an abnormal postexercise ABI. However, this is due in part to limbs with a low TBI having a lower resting ABI on average than limbs with a normal TBI, which also correlates with the probability of an abnormal exercise test result. This study shows that the TBI and the postexercise ABI are not interchangeable for establishing a PAD diagnosis.

Reporting and handling of equivocal imaging findings in diagnostic studies of bone metastasis in prostate cancer.

BACKGROUND: Equivocal scanning results occur. It remains unclear how these results are presented and their management influence diagnostic characteristics. PURPOSE: To investigate the reporting and handling of equivocal imaging findings in diagnostic studies of bone metastases, and to assess the impact on diagnostic performance of the methods used to analyze equivocal findings. The conceptual issue was reified based on two actual observations. MATERIAL AND METHODS: A recent meta-analysis of bone metastases in prostate cancer was conducted and data were obtained from a large clinical trial with a true reference of bone metastasis, where diagnostic characteristics were calculated with equivocal scans handled by: removal; considered malignant; considered benign; and intention-to-diagnose. RESULTS: The meta-analysis included 18 trials where the median proportion of reported equivocal results was 27%. Eleven (61%) studies reported an equivocal option for the index test, 42% reported equivocal results and described how these were analyzed. The clinical trial included 583 prostate cancer patients with 20% equivocal results. The different methods of managing equivocal findings resulted in highly variable outcomes: sensitivity = 85%-100%; specificity = 78%-99%; and positive and negative predictive values = 44%-94% and 97%-100%, respectively. The diagnostic performances obtained using the four methods were differentially susceptible to the proportion of equivocal imaging findings and the prevalence of bone metastases. CONCLUSION: Reporting of equivocal results was inadequate in bone imaging trials. The handling of equivocal findings strongly influenced diagnostic accuracy.

The frequency of thyroid incidental findings and risk of malignancy detected by 68Ga-labeled prostate-specific membrane antigen PET/CT in prostate cancer.

OBJECTIVE: Gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) has become a well-established imaging method for the evaluation of patients with prostate cancer. However, several cases have revealed PSMA uptake in a large variety of conditions other than prostate cancer. Prostate-specific membrane antigen uptake in thyroid cancer has also been reported. The aim of the present study was to systematically investigate the prevalence and clinical significance of thyroid incidental findings in patients undergoing 68Ga-PSMA PET/CT. MATERIALS AND METHODS: We retrospectively identified all patients referred for 68Ga-PSMA PET/CT at the Department of Nuclear Medicine, Aalborg University Hospital, Denmark between May 2015 and May 2019. Patients with increased PSMA uptake in the thyroid gland were included in the analysis. Follow-up included imaging, biochemical, and/or histopathological collected over six months. RESULTS: A total of 341 patients were included. Increased 68Ga-PSMA uptake in the thyroid gland was observed in 13 patients (4%). Focal uptake was observed in seven patients, diffuse uptake in five patients and mixed focal and diffuse uptake in one patient. Malignancy was verified in two patients (2/13 patients, 15%), both patients with focal PSMA uptake. CONCLUSION: Gallium-68-PSMA thyroid incidental findings are rare in prostate cancer patients. However, cases of focal PSMA uptake in the thyroid gland should be further investigated, as these findings may represent metastatic or primary malignancy of the thyroid gland.

Prospective comparison of 68Ga-PSMA PET/CT, 18F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer.

PURPOSE: To prospectively compare diagnostic accuracies for detection of bone metastases by 68Ga-PSMA PET/CT, 18F-NaF PET/CT and diffusion-weighted MRI (DW600-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR). METHODS: Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent 68Ga-PSMA PET/CT, a 18F-NaF PET/CT and a DW600-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm2). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic. RESULTS: Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98-1.00 and 0.89-0.90 for 68Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90-0.98 and 0.90-0.94 for 18NaF PET/CT (n = 67 patients); and 0.25-0.38, 0.87-0.92 and 0.59-0.62 for DW600-MRI (n = 60 patients). The diagnostic performance of DW600-MRI was significantly lower than that of 68Ga-PSMA PET/CT and 18NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between 68Ga-PSMA PET/CT and 18NaF PET/CT (p = 0.65). CONCLUSION: 68Ga-PSMA PET/CT and 18F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW600-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

Prospective evaluation of computer-assisted analysis of skeletal lesions for the staging of prostate cancer.

BACKGROUND: The purpose of this study was to compare the agreement of the bone scan index (BSI) using EXINI BoneBSI versus experts' readings in the initial staging for bone metastasis in prostate cancer. In addition, the diagnostic outcome was assessed in a large subset of patients where a true reference for metastases could be determined based on clinical and biochemical follow-up and/or supplementary imaging. METHODS: A total of 342 patients had a bone scintigraphy as part of routine staging for prostate cancer. Supplementary imaging was obtained at the discretion of the referring urologist. After full recruitment, the BSI and the number of malignant lesions were calculated using EXINI BoneBSI, and three imaging experts independently classified bone status by a dichotomous outcome (M1 for bone metastasis, M0 for no bone metastasis). A true reference was available in a subset of the patients based on post-operative prostate-specific antigen responses after radical prostatectomy and/or supplementary imaging. RESULTS: Software analysis with a BSI > 0 as the cut-off for metastasis showed excellent agreement with expert classification for M1 disease (96% of the patients) but modest agreement for M0 disease (38%). With a BSI > 1, the agreement was 58% for M1 and 98% for M0. Software analyses based on individual European Association of Urology risk classification did not improve the diagnostic performance. Among patients with a true reference, the software showed metastasis in 64% of the M0 patients but correctly classified metastases in all M1 patients. The sensitivity was 100%, the specificity was 36%, the positive predictive value was 12.6% and the negative predictive value was 100% with a BSI >0 compared with 66.7%, 97.8%, 72.7%, and 97.0% with a BSI > 1. CONCLUSION: The diagnostic value of using EXINI Bone for the BSI in the staging of newly diagnosed prostate cancer is limited.

(18)F-fluoride positron emission tomography/computed tomography and bone scintigraphy for diagnosis of bone metastases in newly diagnosed, high-risk prostate cancer patients: study protocol for a multicentre, diagnostic test accuracy study.

BACKGROUND: For decades, planar bone scintigraphy has been the standard practice for detection of bone metastases in prostate cancer and has been endorsed by recent oncology/urology guidelines. It is a sensitive method with modest specificity. (18)F-fluoride positron emission tomography/computed tomography has shown improved sensitivity and specificity over bone scintigraphy, but because of methodological issues such as retrospective design and verification bias, the existing level of evidence with (18)F-fluoride positron emission tomography/computed tomography is limited. The primary objective is to compare the diagnostic properties of (18)F-fluoride positron emission tomography/computed tomography versus bone scintigraphy on an individual patient basis. METHODS/DESIGN: One hundred forty consecutive, high-risk prostate cancer patients will be recruited from several hospitals in Denmark. Sample size was calculated using Hayen's method for diagnostic comparative studies. This study will be conducted in accordance with recommendations of standards for reporting diagnostic accuracy studies. Eligibility criteria comprise the following: 1) biopsy-proven prostate cancer, 2) PSA ≥ 50 ng/ml (equals a prevalence of bone metastasis of ≈ 50% in the study population on bone scintigraphy), 3) patients must be eligible for androgen deprivation therapy, 4) no current or prior cancer (within the past 5 years), 5) ability to comply with imaging procedures, and 6) patients must not receive any investigational drugs. Planar bone scintigraphy and (18)F-fluoride positron emission tomography/computed tomography will be performed within a window of 14 days at baseline. All scans will be repeated after 26 weeks of androgen deprivation therapy, and response of individual lesions will be used for diagnostic classification of the lesions on baseline imaging among responding patients. A response is defined as PSA normalisation or ≥ 80% reduction compared with baseline levels, testosterone below castration levels, no skeletal related events, and no clinical signs of progression. Images are read by blinded nuclear medicine physicians. The protocol is currently recruiting. DISCUSSION: To the best of our knowledge, this is one of the largest prospective studies comparing (18)F-fluoride positron emission tomography/computed tomography and bone scintigraphy. It is conducted in full accordance with recommendations for diagnostic accuracy trials. It is intended to provide valid documentation for the use of (18)F-fluoride positron emission tomography/computed tomography for examination of bone metastasis in the staging of prostate cancer.

Safety and tolerability of regadenoson for myocardial perfusion imaging - first Danish experience.

OBJECTIVES: Evaluating safety and tolerability of the selective A2A receptor agonist, regadenoson, in patients referred for single photon emission computed tomography myocardial perfusion imaging (MPI). DESIGN: Observational study of patients referred for MPI stress testing using a 400 µg regadenoson (Rapiscan(®)) bolus. Hemodynamic variables and severity of adverse events (AE) were recorded before, during, and after administration. RESULTS: A total of 232 patients were included. One or more AE were reported in 90% of patients; the AEs were graded mostly mild to moderate in severity, resolved spontaneously, and were mainly dyspnea, headache, and chest pain. No advanced heart block or bronchospasm were seen. Transient ST-segment changes developed in 10 patients. The maximum increase in heart rate was 19 ± 11 beats/minute. The mean systolic blood pressure decreased from 144 to 139 mmHg (p < 0.0001). Medical intervention was required in three patients: one case with severe hypotension and two cases with chest pain that was relieved with sublingual nitroglycerin. One patient died the day after stress MPI for reasons considered unrelated to regadenoson. CONCLUSION: Regadenoson for MPI is easy to use with a high frequency of AEs, which are generally mild in severity, transient, and resolve spontaneously.