Real-World Experience with 177Lu-PSMA-617 Radioligand Therapy After Food and Drug Administration Approval.

We report our initial real-world experience with 177Lu-PSMA-617 radioligand therapy. Methods: We performed a retrospective review of patients treated with 177Lu-PSMA-617. Pretreatment PSMA PET, laboratory findings, overall survival, a fall in prostate-specific antigen by 50% (PSA50), and toxicities were evaluated. Results: Ninety-nine patients were included. Sixty patients achieved a PSA50. Seven of 18 (39%) patients who did not meet the TheraP PSMA imaging criteria achieved a PSA50. Nineteen of 31 (61%) patients who did not meet the VISION laboratory criteria achieved a PSA50. Sixty-three patients had a delay or stoppage in therapy, which was due to a good response in 19 patients and progressive disease in 14 patients. Of 10 patients with a good response who restarted treatment, 9 subsequently achieved a PSA50 on retreatment. The most common toxicities were anemia (33%) and thrombocytopenia (21%). Conclusion: At our center, patients who did not meet the TheraP PSMA imaging criteria or the VISION laboratory criteria benefited from 177Lu-PSMA-617 radioligand therapy.

Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19.

The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.

Key Factors to Attract More U.S. Diagnostic Radiology Residents into the Field of Nuclear Medicine and Molecular Imaging: A National Survey.

RATIONALE AND OBJECTIVES: To understand the current state of radiology residents' exposure to nuclear medicine and molecular imaging (NM/MI), determine key factors that may attract more trainees into the field, and identify differentiating aspects between those specializing in NM/MI and those who are not. MATERIALS AND METHODS: An anonymous web-based survey was sent to contacts at all diagnostic radiology residency programs in the United States for dissemination to their residents, collecting information about trainees' NM/MI exposure during residency and factors that may attract them to NM/MI. RESULTS: A total of 198 trainees responded to the survey, 34 of whom plan on pursuing a career in NM/MI. Most trainees reported early exposure to NM/MI during residency; most (97.4%) reported ample exposure to general NM/MI and oncologic studies. Less than 3% of trainees reported adequate exposure to therapies, neurological applications, molecular imaging/research advances, and physics. Respondents reported a need for better quality education (38.9%) and exposure to mentors (28.8%) as ways to attract trainees to NM/MI. Routinely encountered clinical pathology was the most interesting for those specializing in NM/MI (29.4%), whereas lifestyle was the most attractive aspect of NM/MI for those not pursuing a career in the field (27.4%). NM/MI-associated research was the least attractive for those specializing in NM/MI (35.3%), while job market concerns was the least attractive aspect for those not specializing in NM/MI (37.2%). Trainees planning to specialize in NM/MI reported higher satisfaction with their orientation to NM/MI during their first clinical rotation compared to those who do not plan to specialize in the field (3.03/5.00 and 2.67/5.00, respectively, p = 0.04). CONCLUSION: This survey highlights several factors that training programs and national societies can target to improve interest in NM/MI among radiology residents. We found that optimized education initiatives, including improved orientation to the field, increased mentoring, and career opportunities are essential levers for recruiting radiology trainees into the NM/MI workforce.

Carbon-11-Labeled Methionine PET/CT in Patients With FDG-Occult Multiple Myeloma: A Prospective Pilot Study.

In a pilot study (ClinicalTrials.gov NCT02646085), seven patients with treated multiple myeloma and negative FDG PET/CT underwent amino acid imaging with 11C-methionine PET/CT. In five participants, 11C-methionine PET/CT showed focal uptake corresponding with lytic lesions; two to 18 lesions were found (SUVmax, 2.8-6.4). Findings indicated a potential role for 11C-methionine PET/CT in detecting residual disease after negative FDG PET/CT, thereby guiding further treatment.

Utility of 18F-Fluciclovine PET/CT for Detecting Prostate Cancer Recurrence in Patients With Low (< 1 ng/mL) or Very Low (< 0.3 ng/mL) Prostate-Specific Antigen Levels.

OBJECTIVE. We reviewed a retrospective series of 126 18F-fluciclovine PET/CT studies of patients with biochemically recurrent prostate cancer at low (< 1 ng/mL) and very low (< 0.3 ng/mL) prostate-specific antigen (PSA) levels. CONCLUSION. The rate of PET/CT positivity was 33% (15/46) in patients with low PSA levels and 0% (0/17) in patients with very low PSA levels. Our results suggest that 18F-fluciclovine PET/CT can be helpful for localizing recurrence in patients with PSA levels between 0.3 and 1 ng/mL and that 18F-fluciclovine PET/CT is not recommended in patients with PSA levels less than 0.3 ng/mL.

Value of SPECT/CT for Sentinel Lymph Node Localization in the Parotid and External Jugular Chain.

OBJECTIVE: Preoperative single-photon emission computed tomography/computed tomography (SPECT/CT) imaging may aid in the localization of sentinel lymph nodes (SLNs) in cutaneous head and neck malignancy and has been rigorously evaluated for deep cervical lymph nodes. The purpose of this study was to assess the sensitivity, specificity, and positive predictive value (PPV) of SPECT/CT for preoperative localization of nodal basins superficial to the sternocleidomastoid muscle, with comparison to deep nodal basins of the neck. STUDY DESIGN: Retrospective review. SETTING: Tertiary care center. SUBJECTS AND METHODS: SPECT/CT images obtained preoperatively for patients undergoing SLN biopsy for cutaneous head and neck malignancy between June 2015 and June 2016 were reviewed by a blinded nuclear medicine physician and head and neck surgeon. SPECT/CT imaging was compared to intraoperatively determined SLN location via gamma probe. Sensitivity, specificity, and positive and negative predictive values were determined and compared for superficial (external jugular [EJ] and parotid) nodes vs level II nodes. RESULTS: Fifty-three patients were included in the study. Most had cutaneous melanoma (69.8%). The PPV of EJ/parotid node identification by SPECT/CT imaging was 85.7%, specificity was 88.9%, and sensitivity was 69.2%. Comparatively, the PPV for level II nodes was 76.9%, specificity was 50%, and sensitivity was 85.7%. No significant difference in SPECT/CT predictive value was identified between EJ/parotid and level II node identification ( P > .05). CONCLUSION: SPECT/CT imaging has strong specificity and positive predictability for preoperative localization of SLN superficial to the sternocleidomastoid muscle in cutaneous head and neck malignancy. SPECT/CT imaging may be a useful radiographic aid for preoperative SLN mapping in this patient population.

C11 Methionine PET (MET-PET) Imaging of Glioblastoma for Detecting Postoperative Residual Disease and Response to Chemoradiation Therapy.

PURPOSE: Response criteria of glioblastoma after chemoradiation do not account for metabolic changes that occur after treatment. The purpose of this study is to evaluate the utility of positron emission tomography (PET) imaging with C11 methionine (MET) (MET-PET) for detecting changes that occur after chemoradiation therapy and the value of molecular biomarkers for predicting the magnitude of metabolic response. METHODS AND MATERIALS: Patients with newly diagnosed glioblastoma undergoing standard chemoradiation treatment were enrolled in this prospective imaging study, with MET-PET scan performed within 3 days after surgical resection and again at 4 weeks after completion of chemoradiation. Near contemporaneous contrast-enhanced magnetic resonance imaging was performed within 2 weeks of each MET-PET scan. MET-PET imaging was analyzed for maximum standardized uptake value (SUV), SUVmean, and SUVvolume on a multimodality workstation. RESULTS: A total of 18 patients underwent baseline postoperative MET-PET imaging, 14 of whom underwent postchemoradiation MET-PET imaging. Among those who showed residual MET-avid disease on immediate postoperative MET-PET scans and underwent postchemoradiation MET-PET imaging (n = 10), mean ΔSUVmax was -40% (range -100% to 0%), mean ΔSUVmean was -35% (range -100% to 0%), and mean ΔSUV volume was -64% (range -100% to 0%). The Δtumor/brain reference was -40% (range -100% to 0%) using SUVmax and -35% (range -100% to 0%) using SUVmean. In contrast, none of the T2-weighted images on contrast-enhanced magnetic resonance imaging showed a >25% reduction in abnormal T2/fluid-attenuated inversion recovery signal on visual assessment. ΔSUVmax, ΔSUVmean, and ΔSUVvolume correlated with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status (P = .01), but not with epidermal growth factor receptor or c-MET amplification status. All patients were IDH-1 wildtype. CONCLUSIONS: MET-PET scanning shows a significant decrease in metabolic signal at 1 month after chemoradiation compared with the immediate postoperative period, even when T2/fluid-attenuated inversion recovery changed little. MGMT promoter methylation status further predicts differential metabolic responses. MET-PET may be a useful tool for delineation of radiation targets and assessment of response.

Fluorodeoxyglucose positron emission tomography for detection of tumor recurrence following radiofrequency ablation in retrospective cohort of stage I lung cancer.

PURPOSE: The goal of this study was to define patterns for tumor recurrence on PET following RFA, compare time to imaging recurrence by PET versus CT, evaluate whether pre-treatment tumor uptake predicts recurrence and propose an optimal post-RFA surveillance strategy. MATERIALS AND METHODS: A retrospective cohort study was performed of biopsy confirmed primary stage I lung cancers treated with RFA. FDG PET and near contemporaneous diagnostic CT imaging pre-ablation, within 30 days post-ablation, and beyond 6 months were independently and retrospectively evaluated for features supportive of recurrence. Time to imaging recurrence by PET (TTR_PET) and by CT (TTR_CT) were determined and compared. FDG avidity of untreated tumors was compared between recurrent and non-recurrent groups. RESULTS: Thirteen recurrences after 72 RFA treatments were confirmed by diagnostic CT. All recurrences were associated with focally intense and increasing FDG uptake beyond 6 months (sensitivity 100%; specificity 98.5%). Mean TTR_PET was 14 months compared to mean TTR_CT of 17 months (not statistically significant). Normalized SUVmax and total lesions glycolysis of lung cancers that recurred after RFA was 4.0 and 6.0, respectively compared to 2.8 and 5.0, respectively for cancers that did not recur (p = .068). CONCLUSION: A pattern of focally intense and increasing FDG PET uptake has high sensitivity and specificity for detecting recurrent lung cancer following RFA. Surveillance after RFA should include a contrast enhanced diagnostic CT at 1 month to diagnose procedural complications, PET at 6 months as a post-treatment metabolic baseline (with diagnostic CT if PET is abnormal) and alternating diagnostic CTs or PET every 6 months for 2 years.

Safety of Administering Furosemide During Nuclear Diuretic Renography in Patients With Sulfonamide Allergies.

OBJECTIVE: We reviewed the safety of nuclear diuretic renography with furosemide in patients with sulfonamide allergies. The electronic health record was used to uncover any drug effects reported within 30 days of diuretic renograms performed between January 2009 and December 2015. CONCLUSION: Eighty-three of 1103 (7.5%) diuretic renograms were performed on patients with sulfonamide allergies. Two instances of minor rash occurred. No serious reactions occurred. Furosemide is associated with an extremely low risk of minor reactions in patients with sulfonamide allergies.

18F-Fluoroestradiol PET/CT Measurement of Estrogen Receptor Suppression during a Phase I Trial of the Novel Estrogen Receptor-Targeted Therapeutic GDC-0810: Using an Imaging Biomarker to Guide Drug Dosage in Subsequent Trials.

Purpose: Evaluate 18F-fluoroestradiol (FES) PET/CT as a biomarker of estrogen receptor (ER) occupancy and/or downregulation during phase I dose escalation of the novel ER targeting therapeutic GDC-0810 and help select drug dosage for subsequent clinical trials.Experimental Design: In a phase I clinical trial of GDC-0810, patients with ER-positive metastatic breast cancer underwent FES PET/CT before beginning therapy and at cycle 2, day 3 of GDC-0810 therapy. Up to five target lesions were selected per patient, and FES standardized uptake value (SUV) corrected for background was recorded for each lesion pretherapy and on-therapy. Complete ER downregulation was defined as ≥90% decrease in FES SUV. The effect of prior tamoxifen and fulvestrant therapy on FES SUV was assessed.Results: Of 30 patients who underwent paired FES-PET scans, 24 (80%) achieved ≥90% decrease in FES avidity, including 1 of 3 patients receiving 200 mg/day, 2 of 4 patients receiving 400 mg/day, 14 of 16 patients receiving 600 mg/day, and 7 of 7 patients receiving 800 mg/day. Withdrawal of tamoxifen 2 months prior to FES PET/CT and withdrawal of fulvestrant 6 months prior to FES PET/CT both appeared sufficient to prevent effects on FES SUV. A dosage of 600 mg GDC-0810 per day was selected for phase II in part due to decreases in FES SUV achieved in phase I.Conclusions: FES PET/CT was a useful biomarker of ER occupancy and/or downregulation in a phase I dose escalation trial of GDC-0810 and helped select the dosage of the ER antagonist/degrader for phase II trials. Clin Cancer Res; 23(12); 3053-60. ©2016 AACR.

Irradiation of FDG-PET-Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Anal Cancer Patients Undergoing Chemoradiation.

PURPOSE: Irradiation of pelvic bone marrow (BM) has been correlated with hematologic toxicity (HT) in patients undergoing chemoradiation for anal cancer. We hypothesized that irradiation of hematologically active bone marrow (ABM) subregions defined by fluorodeoxyglucose (FDG) positron emission tomography (PET) is a principal cause of radiation-associated HT. METHODS AND MATERIALS: The cohort included 45 patients with nonmetastatic anal cancer who underwent FDG-PET imaging prior to definitive chemoradiation with mitomycin-C and 5-fluorouracil. Total bone marrow (TBM) was defined as the external contour of the pelvic bones from the top of lumbar 5 (L5) to the bottom of the ischial tuberosity. Standardized uptake values (SUV) for all voxels within the TBM were quantified and normalized by comparison to normal liver SUV. Subvolumes of the TBM that exhibited the highest and lowest 50% of the SUVs were designated ABM50 and IBM50, respectively. The primary endpoint was the absolute neutrophil count (ANC) nadir during or within 2 weeks of completion of treatment. Multivariate linear modeling was used to analyze the correlation between the equivalent uniform doses (EUD) with an a value of 0.5, 1 (equivalent to mean dose), 3, 7, and 12 to the BM structures and the ANC. RESULTS: Mean ± SD ANC nadir was 0.77 × 10(9)/L (±0.66 × 10(9)/L). Grades 3 and 4 ANC toxicity occurred in 26.7% and 44.4% of patients, respectively. The EUD a parameter of 0.5 was optimal for all BM models indicating high radiation sensitivity. EUD of TBM and ABM50 and IBM50 were all significantly associated with ANC nadir. However, model performance for ABM50 was not superior to that of the TBM and IBM50 models. CONCLUSIONS: Irradiation of pelvic BM was associated with HT. However, FDG-PET-defined ABM models failed to improve model performance compared to the TBM model.

Improving Concordance of MRI and PET/CT Interpretations With Retrospectively Coregistered MRI and PET/CT Data Sets.

This study evaluates if retrospective software-fused magnetic resonance imaging/positron emission tomography (MRI/PET) images can improve concordance of MRI and PET/computed tomography (CT) findings in the pelvis and improve overall lesion detection and characterization, as compared with independent side-by-side interpretation of MRI and PET data sets. Institutional review board approval was obtained for this retrospective study. Our institution's electronic medical record system was examined for pelvic MRI scans and whole-body (18)F-fluorodeoxyglucose-PET/CT scans performed within a 2-month interval between January 2007 and June 2011. PET and MRI data sets for which there were discordant findings on original clinical reports were fused using software (Siemens TrueD, Erlangen, Germany). The fused MRI/PET data sets were reviewed by 2 radiologists for any evidence of metastatic disease in the pelvis. Interpretations were compared with original PET/CT and MRI reports (interpreted side by side), with pathology and imaging follow-up as the reference standard. Overall, 250 pairs of PET/CT and MRI scans were identified in 228 patients. A total of 57 discordant lesions were identified in 31 pairs of scans (12%) in 31 patients (14%). Software fusion resolved the discordance at 3 sites (5%) among 3 patients (10%), including 2 bone sites and a single nodal site. Software-fused MRI/PET is easy to perform and can increase the concordance rate of PET and MRI findings compared with side-by-side interpretation, thereby improving confidence in lesion characterization.

The predictive value of single-photon emission computed tomography/computed tomography for sentinel lymph node localization in head and neck cutaneous malignancy.

OBJECTIVES/HYPOTHESIS: Preoperative localization of sentinel lymph nodes in head and neck cutaneous malignancies can be aided by single-photon emission computed tomography/computed tomography (SPECT/CT); however, its true predictive value for identifying lymph nodes intraoperatively remains unquantified. This study aims to understand the sensitivity, specificity, and positive and negative predictive values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of the head and neck. STUDY DESIGN: Blinded retrospective imaging review with comparison to intraoperative gamma probe confirmed sentinel lymph nodes. METHODS: A consecutive series of patients with a head and neck cutaneous malignancy underwent preoperative SPECT/CT followed by sentinel lymph node biopsy with a gamma probe. Two nuclear medicine physicians, blinded to clinical data, independently reviewed each SPECT/CT. Activity within radiographically defined nodal basins was recorded and compared to intraoperative gamma probe findings. Sensitivity, specificity, and negative and positive predictive values were calculated with subgroup stratification by primary tumor site. RESULTS: Ninety-two imaging reads were performed on 47 patients with cutaneous malignancy who underwent SPECT/CT followed by sentinel lymph node biopsy. Overall sensitivity was 73%, specificity 92%, positive predictive value 54%, and negative predictive value 96%. The predictive ability of SPECT/CT to identify the basin or an adjacent basin containing the single hottest node was 92%. SPECT/CT overestimated uptake by an average of one nodal basin. In the head and neck, SPECT/CT has higher reliability for primary lesions of the eyelid, scalp, and cheek. CONCLUSIONS: SPECT/CT has high sensitivity, specificity, and negative predictive value, but may overestimate relevant nodal basins in sentinel lymph node biopsy.

Clinical evaluation of a mobile digital specimen radiography system for intraoperative specimen verification.

OBJECTIVE: Use of mobile digital specimen radiography systems expedites intraoperative verification of excised breast specimens. The purpose of this study was to evaluate the performance of a such a system for verifying targets. MATERIALS AND METHODS: A retrospective review included 100 consecutive pairs of breast specimen radiographs. Specimens were imaged in the operating room with a mobile digital specimen radiography system and then with a conventional digital mammography system in the radiology department. Two expert reviewers independently scored each image for image quality on a 3-point scale and confidence in target visualization on a 5-point scale. A target was considered confidently verified only if both reviewers declared the target to be confidently detected. RESULTS: The 100 specimens contained a total of 174 targets, including 85 clips (49%), 53 calcifications (30%), 35 masses (20%), and one architectural distortion (1%). Although a significantly higher percentage of mobile digital specimen radiographs were considered poor quality by at least one reviewer (25%) compared with conventional digital mammograms (1%), 169 targets (97%), were confidently verified with mobile specimen radiography; 172 targets (98%) were verified with conventional digital mammography. Three faint masses were not confidently verified with mobile specimen radiography, and conventional digital mammography was needed for confirmation. One faint mass and one architectural distortion were not confidently verified with either method. CONCLUSION: Mobile digital specimen radiography allows high diagnostic confidence for verification of target excision in breast specimens across target types, despite lower image quality. Substituting this modality for conventional digital mammography can eliminate delays associated with specimen transport, potentially decreasing surgical duration and increasing operating room throughput.