[89Zr]Zr-girentuximab for PET-CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial.

BACKGROUND: With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect clear-cell renal cell carcinoma in patients with renal masses remain an unmet need. 89Zr-labelled monoclonal antibody ([89Zr]Zr-girentuximab) has high affinity for carbonic anhydrase 9, a tumour antigen highly expressed in clear-cell renal cell carcinoma. We aimed to evaluate [89Zr]Zr-girentuximab PET-CT imaging for detection and characterisation of clear-cell renal cell carcinoma. METHODS: ZIRCON was a prospective, open-label, multicentre, phase 3 trial conducted at 36 research hospitals and practices across nine countries (the USA, Australia, Canada, the UK, Türkiye, Belgium, the Netherlands, Spain, and France). Patients aged 18 years or older with an indeterminate renal mass 7 cm or smaller (cT1) suspicious for clear-cell renal cell carcinoma and scheduled for nephrectomy received a single dose of [89Zr]Zr-girentuximab (37 MBq ±10%; 10 mg girentuximab) intravenously followed by abdominal PET-CT imaging 5 days (±2 days) later. Surgery was performed no later than 90 days after administration of [89Zr]Zr-girentuximab. Blinded central review, conducted by three independent readers, determined the histology from surgical samples. The coprimary endpoints, determined for each individual reader, were the sensitivity and specificity of [89Zr]Zr-girentuximab PET-CT imaging to detect clear-cell renal cell carcinoma, with histopathological confirmation as standard of truth. Analyses were on the full analysis set of patients, defined as patients who had evaluable PET-CT imaging and a confirmed histopathological diagnosis. The trial is registered with ClinicalTrials.gov, NCT03849118, and EUDRA Clinical Trials Register, 2018-002773-21, and is closed to enrolment. FINDINGS: Between Aug 14, 2019, and July 8, 2022, 371 patients were screened for eligibility, 332 of whom were enrolled. 300 patients received [89Zr]Zr-girentuximab (214 [71%] male and 86 [29%] female). 284 (95%) evaluable patients were included in the primary analysis. The mean sensitivity was 85·5% (95% CI 81·5-89·6) and mean specificity was 87·0% (81·0-93·1). No safety signals were observed. Most adverse events were not or were unlikely to be related to [89Zr]Zr-girentuximab, with most (193 [74%] of 261 events) occurring during or after surgery. The most common grade 3 or worse adverse events were post-procedural haemorrhage (in six [2%] of 261 patients), urinary retention (three [1%]), and hypertension (three [1%]). In 25 (8%) of 300 patients, 52 serious adverse events were reported, of which 51 (98%) occurred after surgery. There were no treatment-related deaths. INTERPRETATION: Our results suggest that [89Zr]Zr-girentuximab PET-CT has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma, which has the potential to be practice changing. FUNDING: Telix Pharmaceuticals.

Prospective investigation of amino acid transport and PSMA-targeted positron emission tomography for metastatic lobular breast carcinoma.

PURPOSE: To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or 18F-FDG positron-emission-tomography (PET)-CT]. METHODS: 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with 18F-fluciclovine and 68Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and 18F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of 18F-fluciclovine and 68Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test. RESULTS: The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. 68Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. 18F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for 18F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between 68Ga-PSMA-11 and standard-of care imaging. 18F-fluciclovine cDR was also significantly higher than 68Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with 18F-fluciclovine (n = 18) was significantly greater than for 68Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021]. CONCLUSION: In this exploratory trial, 18F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to 68Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with 18F-fluciclovine than for 68Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study. CLINICAL TRIAL REGISTRATION: Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280).

Diagnostic Performance and Safety of 18F-rhPSMA-7.3 Positron Emission Tomography in Men With Suspected Prostate Cancer Recurrence: Results From a Phase 3, Prospective, Multicenter Study (SPOTLIGHT).

PURPOSE: SPOTLIGHT (NCT04186845) evaluated diagnostic performance and safety of radiohybrid 18F-rhPSMA-7.3, a novel high-affinity positron emission tomography radiopharmaceutical. MATERIALS AND METHODS: Men with prostate cancer recurrence underwent positron emission tomography/CT 50-70 minutes after intravenous administration of 296±20% MBq 18F-rhPSMA-7.3. To assess the coprimary end points (verified detection rate and combined region-level positive predictive value), 3 blinded, independent central readers evaluated the scans. Verified detection rate is equivalent to the overall detection rate × positive predictive value. Standard of truth was established for each patient using histopathology or confirmatory imaging. Statistical thresholds (lower bounds of the confidence intervals) of 36.5% and 62.5% were prespecified for verified detection rate and combined region-level positive predictive value, respectively. Additional end points included detection rate, verified detection rate, and combined region-level positive predictive value in patients with histopathology standard of truth, and safety. RESULTS: The overall 18F-rhPSMA-7.3 detection rate among all 389 patients with an evaluable scan was 83% (majority read). Among the 366 patients (median prostate-specific antigen 1.27 ng/mL) for whom a standard of truth (histopathology [n=69]/confirmatory imaging only [n=297]) was available, verified detection rate ranged from 51% (95% CI 46.1-56.6) to 54% (95% CI 48.8-59.3), exceeding the prespecified statistical threshold. Combined region-level positive predictive value ranged from 46% (95% CI 42.0-50.3) to 60% (95% CI 55.1-65.5) across the readers, not meeting the threshold. In the subset of patients with histopathology standard of truth, the verified detection rate and combined region-level positive predictive value were both above the prespecified thresholds (majority read, 81% [95% CI 69.9-89.6] and 72% [95% CI 62.5-80.7], respectively). No significant safety concerns were identified. CONCLUSIONS: 18F-rhPSMA-7.3 offers a clinically meaningful verified detection rate for localization of recurrent prostate cancer. Despite missing the coprimary end point of combined region-level positive predictive value, the totality of the data support the potential clinical utility of 18F-rhPSMA-7.3.

Voxel-based dosimetry predicting treatment response and related toxicity in HCC patients treated with resin-based Y90 radioembolization: a prospective, single-arm study.

BACKGROUND: There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC). PURPOSE: To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization. MATERIALS AND METHODS: This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs. RESULTS: N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively. CONCLUSION: In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes. CLINICAL TRIAL NUMBER: NCT04172714.

18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial.

BACKGROUND: Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of 18F-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy. METHODS: In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov, NCT01666808 and is closed to new participants. FINDINGS: From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3·52 years (95% CI 2·98-3·95). PET findings resulted in four patients in the 18F-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35·2-not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached-not reached; 20% of 76 patients) in the 18F-fluciclovine-PET/CT group, and 3 year event-free survival was 63·0% (95% CI 49·2-74·0) in the conventional imaging group versus 75·5% (95% CI 62·5-84·6) for 18F-fluciclovine-PET/CT (difference 12·5; 95% CI 4·3-20·8; p=0·0028). In adjusted analyses, study group (hazard ratio 2·04 [95% CI 1·06-3·93], p=0·0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group). INTERPRETATION: Inclusion of 18F-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. FUNDING: National Institutes of Health/National Cancer Institute, Blue Earth Diagnostics, and Winship Cancer Institute of Emory University.

Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial.

PURPOSE: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 (90Y) (scout90Y) microspheres with those of technetium-99m macroaggregated albumin (MAA) in predicting the therapeutic 90Y (Rx90Y) dose for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout90Y. Rx90Y activity was administered 3 days after mapping. Using paired t test and Pearson correlation, the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), predicted mean tumor dose (TD), and nontumoral liver dose (NTLD) by MAA and scout90Y were compared with those by Rx90Y. Bland-Altman plots compared the level of agreement between the TNR and LSF of scout90Y and MAA with that of Rx90Y. The safety of scout90Y was evaluated by examining the discrepancy in extrahepatic activity between MAA and scout90Y. RESULTS: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx90Y. Scout90Y had a moderate LSF, strong TNR, strong TD, and very strong NTLD in correlation with those of Rx90Y. Furthermore, the TNR and LSF of scout90Y had a stronger agreement with those of Rx90Y than with those of MAA. In the nonsegmental subgroup, MAA had no significant correlation with the TD and NTLD of Rx90Y, whereas scout90Y had a very strong correlation with both of these factors. In the segmental subgroup, both MAA and scout90Y had a strong linear correlation with the TD and NTLD of Rx90Y. CONCLUSIONS: Compared with MAA, scout90Y is a more accurate surrogate for Rx90Y biodistribution for nonsegmental therapies.

82Rubidium chloride positron emission tomography discrimination of recurrent intracranial malignancy from radiation necrosis.

BACKGROUND: Accurate identification and discrimination of post treatment changes from recurrent disease remains a challenge for patients with intracranial malignancies despite advances in molecular and magnetic resonance imaging. We have explored the ability of readily available Rubidium-82 chloride (82RbCl) positron emission tomography (PET) to identify and distinguish progressive intracranial disease from radiation necrosis in patients previously treated with radiation therapy. METHODS: Six patients with a total of 9 lesions of either primary (N.=3) or metastatic (N.=6) intracranial malignancies previously treated with stereotactic radiation surgery (SRS) and persistent contrast enhancement on MRI underwent brain 82RbCl PET imaging. Two patients with arteriovenous malformations previously treated with SRS, also had brain 82RbCl PET imaging for a total of 11 lesions studied. Histological confirmation via stereotactic biopsy/excisional resection was obtained for 9 lesions with the remaining 2 classified as either recurrent tumor or radiation necrosis based on subsequent MRI examinations. 82RbCl PET time activity curve analysis was performed which comprised lesion SUVmax, contralateral normal brain SUVmax, and tumor to background ratios (TBmax). RESULTS: 82RbCl demonstrates uptake greater than normal brain parenchyma in all lesions studied. Time activity curves demonstrated progressive uptake of 82RbCl in all lesions without evidence of washout. While recurrent disease demonstrated a greater mean SUVmax compared to radiation necrosis, no statistically significant difference between lesion SUVmax nor TBmax was found (P>0.05). CONCLUSIONS: 82RbCl PET produces high-contrast uptake of both recurrent disease and radiation necrosis compared to normal brain. However, no statistically significant difference was found between recurrent tumor and radiation necrosis.

Tumor-to-Normal Ratio Relationship between Planning Technetium-99 Macroaggregated Albumin and Posttherapy Yttrium-90 Bremsstrahlung SPECT/CT.

PURPOSE: To quantify the relationship of the tumor-to-normal ratio (TNR) attained from the technetium-99m macroaggregated albumin (MAA) and posttreatment yttrium-90 bremsstrahlung (Y90-Brem) single-photon emission computerized tomography (SPECT)/computer tomography (CT) studies in patients with hepatocellular carcinoma (HCC) treated with glass microspheres. MATERIALS AND METHODS: Retrospectively, a total of 190 consecutive patients with HCC who underwent 204 MAA and Y90-Brem SPECT/CT for glass microsphere Y90 radiation segmentectomy (Y90-RS) or lobar treatment (Y90-RLT) between 2013 and 2018 were included. Semi-automated regions-of-interests were drawn around the targeted tumor and nontumoral liver tissue on the SPECT/CT studies. TNR values from MAA and Y90-Brem SPECT/CT were compared using paired t-tests, Pearson correlation, and median with interquartile ranges (IQR). RESULTS: The mean TNR for MAA and Y90-Brem SPECT/CT was 2.96 ± 1.86 (median, 2.64; IQR, 2.50) and 2.29 ± 1.10 (median, 2.06; IQR, 1.05), respectively (P < .0001). The mean Y90-RLT TNR was 2.88 ± 1.67 (median, 2.59; IQR, 0.83) and 2.17 ± 0.89 (median, 1.98; IQR, 0.81) for MAA and Y90-Brem SPECT/CT, respectively (P < .0001). The mean Y90-RS TNR was 3.02 ± 2.01 (median, 2.87; IQR, 3.01) and 2.39 ± 1.25 (median, 2.11; IQR, 1.28) for MAA and Y90-Brem SPECT/CT, respectively (P = .0003). TNR attained from MAA and Y90 SPECT/CT studies showed a moderate correlation in a positive linear fashion for the overall (r = 0.54; P < .001), Y90-RLT (r = 0.66, P < .001), and Y90-RS cohorts (r = 0.48, P < .001). CONCLUSIONS: The TNR attained from Y90-Brem SPECT/CT is often underestimated, positively correlated, and less variable than that attained from MAA SPECT/CT.

Role of 18F-Fluciclovine and Prostate-Specific Membrane Antigen PET/CT in Guiding Management of Oligometastatic Prostate Cancer: AJR Expert Panel Narrative Review.

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.

[18F]Fluciclovine Positron Emission Tomography/Computerized Tomography for Preoperative Staging in Patients with Intermediate to High Risk Primary Prostate Cancer.

PURPOSE: Accurate preoperative staging of prostate cancer is essential for treatment planning. Conventional imaging is limited in detection of metastases. Our primary aim was to determine if [18F]fluciclovine positron emission tomography/computerized tomography is an early indicator of subclinical metastasis among patients with high risk prostate cancer. MATERIALS AND METHODS: A total of 68 patients with unfavorable intermediate to very high risk prostate cancer without systemic disease on conventional imaging were recruited before robotic radical prostatectomy with extended pelvic lymph node dissection. Diagnostic performance of [18F]fluciclovine positron emission tomography/computerized tomography and conventional imaging for detection of metastatic disease, and correlation of positivity to node and metastatic deposit size were determined. RESULTS: Overall 57 of 68 patients completed the protocol, of whom 31 had nodal metastasis on histology. [18F]Fluciclovine positron emission tomography/computerized tomography sensitivity and specificity in detecting nodal metastasis was 55.3% and 84.8% per patient, and 54.8% and 96.4% per region (right and left pelvis, presacral and nonregional), respectively. Compared with conventional imaging [18F]Fluciclovine positron emission tomography/computerized tomography had significantly higher sensitivity on patient based (55.3% vs 33.3%, p <0.01) and region based (54.8% vs 19.4%, p <0.01) analysis, detecting metastasis in 7 more patients and 22 more regions, with similar high specificity. Four additional patients had distant disease or other cancer detected on [18F] fluciclovine positron emission tomography/computerized tomography which precluded surgery. Detection of metastasis was related to size of metastatic deposits within lymph nodes and overall metastatic burden. CONCLUSIONS: [18F]Fluciclovine positron emission tomography/computerized tomography detects occult metastases not identified on conventional imaging and may help guide treatment decisions and lymph node dissection due to high specificity for metastatic disease.

[18F]Fluciclovine PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging-version 1.0.

The aim of this guideline is to provide standards for the recommendation, performance, interpretation, and reporting of [18F]Fluciclovine PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of [18F]Fluciclovine PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

The Impact of Positron Emission Tomography with 18F-Fluciclovine on the Treatment of Biochemical Recurrence of Prostate Cancer: Results from the LOCATE Trial.

PURPOSE: The prospective, multicenter LOCATE (F Fluciclovine [FACBC] PET/CT in Patients with Rising PSA after Initial Prostate Cancer Treatment) trial assessed the impact of positron emission tomography/computerized tomography with F-fluciclovine on treatment plans in patients with biochemical recurrence of prostate cancer after primary therapy with curative intent. MATERIALS AND METHODS: Men who had undergone curative intent treatment of histologically confirmed prostate cancer but who were suspected to have recurrence based on rising prostate specific antigen levels were enrolled prospectively. Each man had negative or equivocal findings on standard of care imaging. F-fluciclovine positron emission tomography/computerized tomography was performed according to standardized protocols. Treating physicians completed a questionnaire regarding the patient treatment plan before and after scanning, recording changes to the treatment modality (eg salvage radiotherapy to systemic androgen deprivation therapy) as major and changes in a modality (eg modified radiotherapy fields) as other. RESULTS: Between June 2016 and May 2017, 213 evaluable patients with a median age of 67 years and median prostate specific antigen 1.00 ng/ml were enrolled in study. F-fluciclovine avid lesions were detected in 122 of the 213 patients (57%). Overall 126 of the 213 patients (59%) had a change in management after the scan, which were major in 98 of 126 (78%) and in 88 (70%) were informed by positive positron emission tomography/computerized tomography findings. The most frequent major changes were from salvage or noncurative systemic therapy to watchful waiting (32 of 126 cases or 25%), from noncurative systemic therapy to salvage therapy (30 of 126 or 24%) and from salvage therapy to noncurative systemic therapy (11 of 126 or 9%). CONCLUSIONS: F-fluciclovine positron emission tomography/computerized tomography detected 1 or more recurrence sites in the majority of men with biochemical recurrence, frequently resulting in major changes to management plans. Future studies will be planned to determine whether a management change leads to improved outcomes.

Feasibility and Initial Results: Fluciclovine Positron Emission Tomography/Ultrasound Fusion Targeted Biopsy of Recurrent Prostate Cancer.

PURPOSE: We assessed the feasibility and cancer detection rate of fluciclovine (18F) positron emission tomography-ultrasound fusion targeted biopsy vs standard template biopsy in the same patient with biochemical failure after nonsurgical therapy for prostate cancer. MATERIALS AND METHODS: A total of 21 patients with a mean ± SD prostate specific antigen of 7.4 ± 6.8 ng/ml and biochemical failure after nonoperative prostate cancer treatment underwent fluciclovine (18F) positron emission tomography-computerized tomography (mean 364.1 ± 37.7 MBq) and planning transrectal prostate ultrasound with 3-dimensional image reconstruction. Focal prostatic activity on positron emission tomography was delineated and co-registered with planning ultrasound. During the subsequent biopsy session computer generated 12-core template biopsies were performed and then fluciclovine defined targets were revealed and biopsied. Histological analysis of template and targeted cores were completed. RESULTS: Template biopsy was positive for malignancy in 6 of 21 patients (28.6%), including 10 of 124 regions and 11 of 246 cores, vs targeted biopsy in 10 of 21 (47.6%), including 17 of 50 regions and 40 of 125 cores. Five of 21 patients had positive findings on targeted biopsy only and 1 of 21 had positive findings on template biopsy only. An additional case was upgraded from Grade Group 2 to 3 on targeted biopsy. Extraprostatic disease was detected in 8 of 21 men (38.1%) with histological confirmation in all 3 who underwent lesion biopsy. CONCLUSIONS: Fluciclovine positron emission tomography real-time ultrasound fusion guidance for biopsy is feasible in patients with biochemical failure after nonsurgical therapy for prostate cancer. It identifies more recurrent prostate cancer using fewer cores compared with template biopsy in the same patient. Further study is required to determine in what manner targeted biopsy may augment template biopsy of recurrent prostate cancer.

Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for imaging of gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0.

These joint practice guidelines, or procedure standards, were developed collaboratively by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the working group for Response Assessment in Neurooncology with PET (PET-RANO). Brain PET imaging is being increasingly used to supplement MRI in the clinical management of glioma. The aim of these standards/guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting and reporting the results of brain PET imaging in patients with glioma to achieve a high-quality imaging standard for PET using FDG and the radiolabelled amino acids MET, FET and FDOPA. This will help promote the appropriate use of PET imaging and contribute to evidence-based medicine that may improve the diagnostic impact of this technique in neurooncological practice. The present document replaces a former version of the guidelines published in 2006 (Vander Borght et al. Eur J Nucl Med Mol Imaging. 33:1374-80, 2006), and supplements a recent evidence-based recommendation by the PET-RANO working group and EANO on the clinical use of PET imaging in patients with glioma (Albert et al. Neuro Oncol. 18:1199-208, 2016). The information provided should be taken in the context of local conditions and regulations.

PPV of Bone Uptake of 18F-Flotufolastat: Evaluation Using SPOTLIGHT Study Data.

Plain language summary (for Research Letters only): Based on data from the phase III SPOTLIGHT study, bone PPV with 18F-flotufolastat PET/CT in patients with recurrent prostate cancer was 63-80% across readers, comparable with the bone PPV of a previously FDA-approved 18F-labelled PSMA radiopharmaceutical. Evaluation of bone uptake should incorporate interpretive guidelines, clinical context, and cross-sectional imaging correlation.

Fluorine-18-Labeled Fluciclovine PET/CT in Clinical Practice: Factors Affecting the Rate of Detection of Recurrent Prostate Cancer.

OBJECTIVE. The purpose of this study is to show the performance and evaluate the factors influencing the positivity rate (PR) of commercially produced 18F-fluciclovine PET/CT in the detection of recurrent prostate cancer in clinical practice. MATERIALS AND METHODS. We performed a retrospective cohort study of 152 men who had suspected biochemical recurrence of prostate cancer after receiving initial treatment and underwent fluciclovine PET/CT. PRs were calculated for whole-body, prostate and prostate bed, and extraprostatic locations. The influence of different factors, such as the absolute prostate-specific antigen (PSA) level, PSA kinetics, the Gleason score, and Gleason grade groups, on the PR was evaluated. RESULTS. The overall PR was 81% (123/152) for the whole body, 61% (92/152) for the prostate and prostate bed, and 55% (83/152) for extraprostatic locations. There was a linear increase in the PR with an increasing PSA level (p < 0.001). For the whole body, the PR for PSA levels of less than 1 ng/mL, 1 to less than 2 ng/mL, 2 to less than 5 ng/mL, and 5 or more ng/mL were 58% (32/55), 87% (13/15), 100% (39/39), and 92% (35/38), respectively. No statistically significant linear trend was found between the PR and the PSA level doubling time (p > 0.05). In addition, no statistically significant linear trend was found between the PR and increasing Gleason grade group. However, for every 1-unit increase in a patient's Gleason score, the odds of a positive finding in the extraprostatic location increased by 49% (p < 0.05). CONCLUSION. Commercially produced fluciclovine PET/CT has a high PR for detection of prostate cancer recurrence and is positively correlated with increasing PSA levels. For extraprostatic disease, the PR increases with higher Gleason scores.

Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques.

The detection of viral dynamics and localization in the context of controlled HIV infection remains a challenge and is limited to blood and biopsies. We developed a method to capture total-body simian immunodeficiency virus (SIV) replication using immunoPET (antibody-targeted positron emission tomography). The administration of a poly(ethylene glycol)-modified, (64)Cu-labeled SIV Gp120-specific antibody led to readily detectable signals in the gastrointestinal and respiratory tract, lymphoid tissues and reproductive organs of viremic monkeys. Viral signals were reduced in aviremic antiretroviral-treated monkeys but detectable in colon, select lymph nodes, small bowel, nasal turbinates, the genital tract and lung. In elite controllers, virus was detected primarily in foci in the small bowel, select lymphoid areas and the male reproductive tract, as confirmed by quantitative reverse-transcription PCR (qRT-PCR) and immunohistochemistry. This real-time, in vivo viral imaging method has broad applications to the study of immunodeficiency virus pathogenesis, drug and vaccine development, and the potential for clinical translation.

Current Clinical Practice Patterns of Self-Identified Nuclear Medicine Specialists.

OBJECTIVE: The objective of our study was to study patterns of services rendered by U.S. physicians who self-identify as nuclear medicine (NM) specialists. MATERIALS AND METHODS: Recent Medicare physician claims and demographic files were obtained and linked. NM specialists were defined as physicians self-identifying NM as their primary specialty on claims or as any of their specialties during enrollment. Using other self-identified specialties, we classified physicians as nuclear radiologists, nuclear cardiologists, exclusively NM physicians, or Others. Our primary outcome measure was the percentage of NM effort (in work relative value units [WRVUs]) per physician per specialty group. Secondary outcome measures included physician sociodemographic parameters and most common uniquely rendered services. RESULTS: Nationally, 1583 physicians self-identified as NM specialists during the calendar years 2012 through 2015. The distribution of WRVUs attributed to NM varied widely by specialty group; most nuclear radiologists and nuclear cardiologists devoted 10% or less of their effort to NM services whereas most NM physicians devoted 90% or more of their effort to NM services. NM specialists were most commonly nuclear radiologists (52.2%) and men (80.3%) and practiced in urban (98.4%) and nonacademic settings (62.9%). NM physicians interpreted more general NM studies, nuclear radiologists interpreted more cross-sectional imaging studies, and nuclear cardiologists interpreted mostly nuclear cardiology studies, with a majority of their overall work attributed to clinical evaluation and management (E/M). E/M services accounted for less than 2% of WRVUs for both nuclear radiologists and NM physicians. CONCLUSION: The work patterns of U.S. NM specialists is highly variable. Most NM physicians practice 90% or more NM, whereas most nuclear radiologists and nuclear cardiologists practice 10% or less NM. Commonly performed services vary considerably by specialty group.