A VISION Substudy of Reader Agreement on 68Ga-PSMA-11 PET/CT Scan Interpretation to Determine Patient Eligibility for 177Lu-PSMA-617 Radioligand Therapy.

[ 68Ga]Ga-PSMA-11 ( 68Ga-PSMA-11) is used to identify prostate-specific membrane antigen (PSMA)-positive tumors on PET scans. In the VISION study, 68Ga-PSMA-11 was used to determine the eligibility of patients with metastatic castration-resistant prostate cancer for treatment with [177Lu]Lu-PSMA-617 (177Lu-PSMA-617), based on predefined read criteria. This substudy aimed to investigate the interreader variability and intrareader reproducibility of visual assessments of 68Ga-PSMA-11 PET/CT scans using the VISION read criteria and evaluate the agreement between read results for this and the VISION study. Methods: In VISION, 68Ga-PSMA-11 PET/CT scans were centrally read as inclusion cases if they had at least 1 PSMA-positive lesion and no PSMA-negative lesions that fulfilled the exclusion criteria. In this substudy, 125 PET/CT scans (75 inclusion and 50 exclusion cases) were randomly selected from VISION and retrospectively assessed by 3 independent central readers. A random subset of 20 cases (12 inclusion and 8 exclusion cases) was recoded for assessment of intrareader reproducibility. Classification of cases as inclusion or exclusion cases was based on the VISION read criteria. Overall interreader variability was assessed by Fleiss κ-statistics, and pairwise variability and intrareader reproducibility were assessed by Cohen κ-statistics. Results: For interreader variability, the readers agreed on 77% of cases (overall average agreement rate, 0.85; Fleiss κ, 0.60 [95% CI, 0.50-0.70]). The pairwise agreement rate was 0.82, 0.88, and 0.84, and the corresponding Cohen κ was 0.54 (95% CI, 0.38-0.71), 0.67 (95% CI, 0.52-0.83), and 0.59 (95% CI, 0.43-0.75), respectively. For intrareader reproducibility, the agreement rate was 0.90, 0.90, and 0.95, and the corresponding Cohen κ was 0.78 (95% CI, 0.49-0.99), 0.76 (95% CI, 0.46-0.99), and 0.89 (95% CI, 0.67-0.99), respectively. The number of actual VISION inclusion cases out of the total number of cases scored as inclusion in this substudy was 71 of 93 (agreement rate, 0.76; 95% CI, 0.66-0.85) for reader 1, 70 of 88 (0.80; 0.70-0.87) for reader 2, and 73 of 96 (0.76; 0.66-0.84) for reader 3. All readers agreed on 66 of 75 VISION inclusion cases. Conclusion: Moderate-to-substantial interreader agreement and substantial-to-almost perfect intrareader reproducibility for 68Ga-PSMA-11 PET/CT scan assessment using the VISION read criteria were observed. The read rules applied in VISION can be readily learned and demonstrate good reproducibility.

PET Imaging of Tumor Hypoxia in Head and Neck Cancer: A Primer for Neuroradiologists.

Tumor hypoxia is a known independent prognostic factor for adverse patient outcomes in those with head and neck cancer. Areas of tumor hypoxia have been found to be more radiation resistant than areas of tumor with normal oxygenation levels. Hypoxia imaging may serve to help identify the best initial treatment option and to assess intratreatment monitoring of tumor response in case treatment changes can be made. PET imaging is the gold standard method for imaging tumor hypoxia, with 18F-fluoromisonidazole the most extensively studied hypoxic imaging tracer. Newer tracers also show promise.

1-11C-acetate kinetics of prostate cancer.

UNLABELLED: (18)F-FDG is in widespread use in cancer imaging but has limited utility in staging and monitoring of prostate cancer. 1-(11)C-Labeled acetate, a substrate for the citric acid cycle, is superior. The kinetics of prostate tumors were investigated. METHODS: Ten patients with primary prostate cancer, 10 with recurrent tumor, and 2 men with benign prostate hypertrophy were studied. After administration of 5.5 MBq/kg 1-(11)C-acetate, dynamic PET of the pelvis was acquired for 20 min. Images were reconstructed with iterative algorithms, and corrections for attenuation and scatter were applied. Factor analysis produced factor images, representing iliac vessels and the prostate from which blood-input and tissue-output functions were derived with simple thresholding techniques. Five different kinetic models were applied to the dynamic data to estimate the rate constants. RESULTS: The standard 3-compartment, 2-tissue model was able to describe 1-(11)C-acetate kinetics of the prostate. The model could be reduced to 3 parameters by setting the tissue blood fraction and release from the second tissue compartment (k(4)) to zero. Correction for metabolites appeared to be necessary. This reduced model performed marginally better than a 2-compartment model. A significant correlation was found between the influx rate constant (K) and acetate uptake (standardized uptake value) for primary tumors (r = 0.91), whereas there was no correlation for recurrent tumors (r = -0.17). Patlak graphical analysis provided accurate parameter estimates. CONCLUSION: A 3-compartment, 3-parameter model is able to describe adequately the acetate kinetics in prostate cancer. Significant differences between primary and recurrent cancer were found for transport k(1), influx K, distribution volume V(d), as well as early (6-10 min) and late (15-20 min) 1-(11)C-acetate uptake.

The Effect of Electroencephalography Leads on Image Quality in Cerebral Perfusion SPECT and 18F-FDG PET/CT.

Cerebral perfusion SPECT and 18F-FDG PET/CT are commonly performed diagnostic procedures for patients with epilepsy. Individuals undergoing these tests are often inpatients with electroencephalography leads. We have routinely removed these leads because of concern that they would lead to imaging artifacts. The leads would then be replaced at the conclusion of the scan. The goal of our study was to determine whether the electroencephalography leads actually do cause artifacts that can lead to erroneous scan interpretation or make the scan uninterpretable. Methods: 18F-FDG PET/CT and 99mTc-pertechnetate SPECT were performed on a 2-dimensional brain phantom. The phantom was scanned with standard leads, CT/MR-compatible leads, and no leads. The quality of the images was ranked by 3 experienced nuclear medicine physicians, who then determined whether they could differentiate each of the scans from a scan in which it was known that no leads were present. Results: No differences could be detected between scans obtained without leads and scans obtained with either set of leads. The standard electroencephalography leads did create artifacts in the CT portion of the PET/CT images, whereas the CT/MR-compatible leads did not. Conclusion: This phantom study suggests that electroencephalography leads, whether standard or CT/MR-compatible, do not need to be removed for SPECT or PET procedures. Further study evaluating the effect on actual patient scans would be of value to support this conclusion.

The spectrum of positive scan patterns in parathyroid scintigraphy.

Parathyroid scintigraphy provides the clinician treating primary hyperparathyroidism with valuable information regarding the presence and location of parathyroid adenomas. In dual-phase imaging of the parathyroid glands, a widely employed technique that exploits the radiotracer washout characteristics of parathyroid adenomas, images are typically obtained at 20 minutes after administration of the radiotracer (Tc-99m sestamibi or Tc-99m tetrofosmin) and again at 2 hours after injection. Additional imaging of the thyroid is frequently performed to localize thyroid tissue, using Tc-99m pertechnetate or iodine-123.A positive examination can display one of several different patterns; a focus of increased radiotracer activity representing a parathyroid adenoma may be detected on the initial images, on the delayed images, or both. On the thyroid scan, the parathyroid adenoma (if it is discernible) may appear as a cold defect or a persistently hot focus. In our retrospective review of 148 consecutive patients over a 2-year period, 74 examinations were positive and had pathologic confirmation. These examinations were divided into 4 patterns: I (hot focus seen on initial and delayed images, and not on thyroid scan), II (hot focus seen only in initial images), III (hot focus seen only on delayed images), and IV (hot focus seen on initial, delayed and thyroid scan images). Results were as follows: pattern I, 88% (65/74); pattern II, 7% (5/74); pattern III, 3% (2/74); and pattern IV, 3% (2/74). Parathyroid adenomas produce several different patterns on dual-phase scintigraphy. To interpret the examination correctly, it is important for the radiologist to be aware of these patterns of positivity.

Use of SPECT/CT to confirm inconclusive gastric emptying scintigraphy results.

A 70-year-old man with cramping, abdominal pain, and diarrhea for 5 months after revision of a Nissen fundoplication underwent further evaluation with solid gastric emptying scintigraphy. On sequential planar images, we were uncertain if activity was present within the stomach or within loops of small bowel. SPECT/CT performed at 4 hours was used to localize the tracer, confirming its presence within the stomach.

Subdiaphragmatic gallstone mimicking hepatic malignancy on FDG PET/CT.

A 70-year-old man underwent an FDG PET/CT for a possible primary liver malignancy or metastasis found on an abdominal MRI obtained as part of a workup for intermittent abdominal pain. The MRI showed an enhancing lesion at the dome of the right lobe of the liver. The lesion was FDG avid with a discrete central calcification. In conjunction with the patient's history of laparoscopic cholecystectomy 1 year prior, the findings were consistent with inflammation around a migrated subdiaphragmatic gallstone. One month after the scan, a CT-guided percutaneous biopsy of this lesion revealed chronic inflammatory cells with no evidence of malignancy.

Radiation dose estimates in humans for (11)C-acetate whole-body PET.

UNLABELLED: 11C-Acetate is currently being investigated as a new tracer for imaging neoplasms, most notably prostate cancer and its metastases. Previously reported dose estimates for (11)C-acetate prepared by the Oak Ridge Institute for Science and Education (ORISE) were based on a simple 3-compartment model in which all activity not measured in blood or excretion via breath was assumed to reside in the heart. Because all organs are involved in acetate metabolism to some extent, these estimates might overestimate heart and underestimate other organ dosimetry. Dynamic whole-body (11)C-acetate PET was therefore performed on 6 healthy human volunteers. Measured dose estimates for all target organs were compared with the existing ORISE values. METHODS: After transmission scanning had been performed for measured attenuation, 525 MBq of (11)C-acetate were injected intravenously, and 5 sequential whole-body emission scans were obtained from the head to mid thighs. Regions of interest were drawn to encompass the entire activity in all visible organs at each time point. Time-activity data were fit in a least-squares sense to obtain residence times. Absorbed dose estimates were determined using MIRDOSE3.1 software. RESULTS: The effective dose was 0.0049 mSv/MBq. The organs receiving the highest absorbed doses were the pancreas (0.017 mGy/MBq), bowel (0.011 mGy/MBq), kidneys (0.0092 mGy/MBq), and spleen (0.0092 mGy/MBq). No urinary excretion of tracer was measurable. CONCLUSION: Using these new estimates for (11)C-acetate dosimetry, the maximum injected activity under Radioactive Drug Research Committee limits can be raised up to 5-fold over the limit imposed by the previous ORISE estimates. A higher injected activity would improve counting statistics and, it is hoped, overall image quality and tumor detection with whole-body (11)C-acetate PET.

The impact of PET on the management of lung cancer: the referring physician's perspective.

UNLABELLED: (18)F-FDG PET is a molecular whole-body imaging modality that is increasingly being used for diagnosing, staging, and restaging cancer. The objective of this study was to determine referring physicians' perspectives on the impact of (18)F-FDG PET on staging and management of lung cancer. METHODS: A questionnaire was sent to the 292 referring physicians of 744 consecutive patients with known or suspected lung cancer who were evaluated with PET. Questionnaires on 274 patients were returned (response rate, 37%). Management changes were categorized as intermodality (e.g., surgery to medical, surgery to radiation, and medical to no treatment) or intramodality (e.g., altered medical, surgical, or radiotherapy approach). RESULTS: The primary reasons for PET referral were staging of lung cancer in 61% of patients, diagnosis in 20%, and monitoring of therapy or the course of disease in 6%. Physicians reported that PET caused them to change their decision on clinical stage in 44% of all patients: The disease was upstaged in 29% and downstaged in 15%. PET resulted in intermodality management changes in 39% of patients, whereas 15% had an intramodality change. CONCLUSION: This survey-based study of referring physicians suggests that PET has a major impact on staging and management of lung cancer.

The impact of 2-deoxy-2[18F] fluoro-D-glucose whole body positron emission tomography for managing patients with melanoma: the referring physician's perspective.

PURPOSE: Whole body positron emission tomography (PET) imaging with 2-deoxy-2[18F]fluoro-D-glucose (FDG) has been used successfully to diagnose and stage melanoma. The impact of FDG-PET, however, on patient stage and management from the referring physicians' perspective is unknown. PROCEDURES: A questionnaire was sent to referring physicians to investigate whether and how PET altered clinical decision in treatment of melanoma patients. Surveys were sent to referring physicians of every melanoma patient who had a PET scan performed at UCLA or the Northern California PET Imaging Center (NCPIC). Data were used to evaluate the impact of FDG-PET on clinical management of melanoma patients based on pre-PET and post-PET staging. Management changes were classified as inter-modality if therapy changed from one modality to another or intra-modality if changes were made within a treatment modality. RESULTS: Fifty-one questionnaires (response rate of 35%) have been received to date. Referring physicians indicated that whole body FDG-PET changed the clinical stage in 15 out of 51 (29%) patients: 10 (20%) were up-staged and five (10%) were down-staged. The PET findings resulted in inter-modality management changes in 15 out of 51 patients (29%). Intra-modality management change occurred in nine patients (18%). CONCLUSION: From the referring physicians' perspective, FDG-PET has a major impact and results in management changes in 53% of patients with melanoma.

Emerging technologies in uroradiologic imaging.

Advances in imaging technologies have readily been incorporated into the practice of urology and have led to important advances in patient care and outcomes. In the area of oncology, advances in radiologic imaging are improving the ability of the urologist to diagnose and monitor urologic malignancies. Some of these technologies include positron emission tomography (PET), intraoperative ultrasound (IUS), 3-dimensional computerized tomography (3D-CT), and magnetic resonance spectroscopy (MRS). We provide an overview of these four emerging imaging modalities and their potential applications and limitations in the diagnosis and management of urologic malignancy.

123I MIBG appearance of severe renal artery stenosis.

We describe a patient with labile hypertension and elevated metanephrines who underwent 123Iodine metaiodobenzylguanidine (MIBG) for the detection of a possible paraganglioma. The scan revealed markedly abnormal diffusely increased activity in the right renal parenchyma. A CT angiogram showed severe renal artery stenosis of an atrophic-appearing right kidney and delayed enhancement of the right kidney, consistent with renal dysfunction due to renal artery stenosis.

Tracheal metastasis from melanoma detected with 18F-FDG PET/CT.

A 58-year-old man with a history of stage IIIB melanoma of the right arm initially treated 4 years prior presented with new onset cough and hemoptysis. Bronchial washings were positive for melanoma. The PET/CT study showed a hypermetabolic nodule in the posterior mid-trachea. These findings indicate metastatic melanoma to the trachea. No other metastatic foci were evident. This allowed for endoscopic laser ablation of the metastatic focus.

Reporting guidance for oncologic 18F-FDG PET/CT imaging.

The written report (or its electronic counterpart) is the primary mode of communication between the physician interpreting an imaging study and the referring physician. The content of this report not only influences patient management and clinical outcomes but also serves as legal documentation of services provided and can be used to justify medical necessity, billing accuracy, and regulatory compliance. Generating a high-quality PET/CT report is perhaps more challenging than generating a report for other imaging studies because of the complexity of this hybrid imaging modality. This article discusses the essential elements of a concise and complete oncologic (18)F-FDG PET/CT report and illustrates these elements through examples taken from routine clinical practice.

Colon cancer metastatic to a urachus diagnosed by PET/CT.

A 50-year-old man presented with a mass in the transverse colon diagnosed by colonoscopy. He underwent a left hemicolectomy and was diagnosed with a moderately differentiated adenocarcinoma penetrating into the pericolic adipose but no lymph node metastases. His course was uneventful with enrollment in a monoclonal antibody research treatment protocol. Eight years later, he presented with hematuria. A PET/CT demonstrated a hypermetabolic right external iliac lymph node and a hypermetabolic mass within a urachal remnant. The mass was excised and pathologically proven to represent a metastasis from the original primary tumor.

Langerhans cell histiocytosis of the auditory canal detected by 18F-FDG PET/CT.

A 24-year-old woman presented with recurrent bilateral ear infections since childhood and a more recent history of partial hearing loss, discharge, and ear pain. Biopsy of the left external auditory canal revealed Langerhans cell histiocytosis. An F-FDG PET/CT was done to look for additional sites of disease. Increased metabolic activity was seen within both external ear canals.

Bexarotene plus erlotinib suppress lung carcinogenesis independent of KRAS mutations in two clinical trials and transgenic models.

The rexinoid bexarotene represses cyclin D1 by causing its proteasomal degradation. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib represses cyclin D1 via different mechanisms. We conducted a preclinical study and 2 clinical/translational trials (a window-of-opportunity and phase II) of bexarotene plus erlotinib. The combination repressed growth and cyclin D1 expression in cyclin-E- and KRAS/p53-driven transgenic lung cancer cells. The window-of-opportunity trial in early-stage non-small-cell lung cancer (NSCLC) patients (10 evaluable), including cases with KRAS mutations, repressed cyclin D1 (in tumor biopsies and buccal swabs) and induced necrosis and inflammatory responses. The phase II trial in heavily pretreated, advanced NSCLC patients (40 evaluable; a median of two prior relapses per patient (range, 0-5); 21% with prior EGFR-inhibitor therapy) produced three major clinical responses in patients with prolonged progression-free survival (583-, 665-, and 1,460-plus days). Median overall survival was 22 weeks. Hypertriglyceridemia was associated with an increased median overall survival (P = 0.001). Early PET (positron emission tomographic) response did not reliably predict clinical response. The combination was generally well tolerated, with toxicities similar to those of the single agents. In conclusion, bexarotene plus erlotinib was active in KRAS-driven lung cancer cells, was biologically active in early-stage mutant KRAS NSCLC, and was clinically active in advanced, chemotherapy-refractory mutant KRAS tumors in this study and previous trials. Additional lung cancer therapy or prevention trials with this oral regimen are warranted.