18F-Flotufolastat Positron Emission Tomography in African American Patients With Suspected Prostate Cancer Recurrence: Findings From the Phase 3 SPOTLIGHT Study.

Purpose: Although African American (AA) patients are disproportionately affected by prostate cancer, they are often underrepresented in oncology clinical trials. The SPOTLIGHT study (NCT04186845) assessed the novel diagnostic positron emission tomography radiopharmaceutical, 18F-flotufolastat (18F-rhPSMA-7.3), in patients with recurrent prostate cancer. The proportion of AA patients enrolled in SPOTLIGHT (17%) was greater than typically enrolled in oncology trials (8.5%) and was representative of the US population (14%). This post hoc analysis of SPOTLIGHT evaluates the diagnostic performance of 18F-flotufolastat in AA patients. Methods and Materials: Patients underwent positron emission tomography/computed tomography 50 to 70 minutes after intravenous administration of 296 MBq 18F-flotufolastat. Three blinded readers evaluated all images, with the majority read (agreement of ≥2 readers) result reported here. Standard of truth (SoT) was established with histopathology or correlative imaging. Data from AA patients were evaluated to determine the 18F-flotufolastat overall detection rate (DR), positive predictive value (PPV), and verified DR (VDR). VDR (SoT-verified) is equivalent to DR × PPV. Results: In total, 61 of 366 (17%) patients were AAs. Although baseline characteristics were broadly similar, fewer AA patients (56%) had undergone prostatectomy than non-AA patients (82%). The patient-level DR was 93% (57/61) in AA patients, increasing from 67% at prostate-specific antigen <0.5 ng/mL to 100% at prostate-specific antigen ≥10 ng/mL. Patient-level DR was marginally lower in all other patients (87%, 264/305). However, when stratifying by prior treatment, DRs were similar across ethnic groups in postprostatectomy patients, but in patients with intact prostates, AA patients had higher prostate DR than non-AA patients. SoT-verification (predominantly with conventional imaging [79%]) gave a VDR of 64% and PPV of 68% in AA patients, versus 55% and 64%, respectively, in all other patients. Conclusions: 18F-Flotufolastat DRs were marginally higher in AA patients than in all other patients enrolled in SPOTLIGHT. High VDR and PPV were also achieved in AA patients from across all participating centers, indicating the broad applicability of newly US Food and Drug Administration-approved 18F-flotufolastat to the US population as a whole.

Comparison of FDG-PET/CT and CT for delineation of lumpectomy cavity for partial breast irradiation.

PURPOSE: The success of partial breast irradiation critically depends on proper target localization. We examined the use of fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) for improved lumpectomy cavity (LC) delineation and treatment planning. METHODS AND MATERIALS: Twelve breast cancer patients underwent FDG-PET/CT on a GE Discovery scanner with a median time from surgery to PET/CT of 49 days. The LC was contoured on the CT scan by a radiation oncologist and, together with a nuclear medicine physician, on the PET/CT scan. The volumes were calculated and compared in each patient. Treatment planning target volumes (PTVs) were calculated by expanding the margin 2 cm beyond the LC, maintaining a 5-mm margin from the skin and chest wall, and the treatment plans were evaluated. In addition, a study with a patient-like phantom was conducted to evaluate the effect that the window/level settings might have on contouring. RESULTS: The margin of the LC was well visualized on all FDG-PET images. The phantom results indicated that the difference between the known volume and the FDG-PET-delineated volume was <10%, regardless of the window/level settings. The PET/CT volumes were larger than the CT volumes in all cases (median volume ratio, 1.68; range, 1.24-2.45; p = 0.004). The PET/CT-based PTVs were also larger than the CT-based PTV (median volume ratio, 1.16; range, 1.08-1.64; p = 0.006). In 9 of 12 patients, a CT-based treatment plan did not provide adequate coverage of the PET/CT-based PTV (99% of the PTV received <95% of the prescribed dose), resulting in substantial cold spots in some plans. In these cases, treatment plans were generated which were specifically designed to cover the larger PET/CT-based PTV. Although these plans showed an increased dose to the normal tissues, the increases were modest: the non-target breast volume receiving > or =50 Gy, lung volume receiving > or =30 Gy, and heart volume receiving > or =5 Gy increased by 5.7%, 0.8%, and 0.2%, respectively. The normal tissue dose-volume objectives were still met with these plans. CONCLUSION: The results of our study have shown that FDG-PET/CT can be used to define the LC volume. The increased FDG uptake was likely a result of postoperative inflammation in the LC. The targets defined using PET/CT were significantly larger than those defined with CT alone. Our results have shown that treatment plans can be generated to cover these larger PET/CT target volumes with only a modest increase in irradiated tissue volume compared with CT-determined PTVs.

Visualization of brown adipose tissue with 99mTc-methoxyisobutylisonitrile on SPECT/CT.

UNLABELLED: Brown adipose tissue (BAT) is retained into adulthood in some patients. It has been imaged using several radiopharmaceuticals, including (18)F-FDG. Using SPECT/CT, we assessed whether and how frequently uptake of (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) was present in expected locations of BAT. METHODS: A total of 205 SPECT/CT scans using (99m)Tc-MIBI for parathyroid imaging were reviewed for the presence of (99m)Tc-MIBI uptake in expected locations of BAT. RESULTS: We detected (99m)Tc-MIBI uptake in BAT in 13 of 205 patients (6.3%). When BAT was visualized, it was detected on both early and delayed scans. The patients with (99m)Tc-MIBI uptake in BAT were younger than the patients with no (99m)Tc-MIBI uptake (P=0.044). CONCLUSION: Uptake of (99m)Tc-MIBI in BAT is relatively common in this adult patient population and should not be confused with (99m)Tc-MIBI-avid-tumors. SPECT/CT can be useful for defining such tracer uptake as a normal physiologic variant.

Attenuation correction in myocardial perfusion SPECT/CT: effects of misregistration and value of reregistration.

UNLABELLED: The accuracy of myocardial perfusion SPECT improves with attenuation correction. Algorithms for attenuation correction in hybrid SPECT/CT systems have the potential for misregistration of emission and transmission scans because CT and SPECT are obtained sequentially. Misregistration will influence regional tracer distribution and may reduce diagnostic accuracy. This study focused on the role of misregistration in cardiac SPECT/CT and the performance of a software-based approach for reregistration. METHODS: We included 105 consecutive patients who underwent clinical myocardial perfusion imaging on a SPECT/CT system. Images were quantitatively assessed for misregistration using fusion software. Results were recorded in millimeters in the x-, y-, and z-axes. Regional tracer uptake in 6 segments (anterior, septal, inferior, lateral, anteroapical, and inferoapical) for noncorrected and attenuation-corrected images before and after reregistration was obtained from polar maps. To determine the relative influence of misregistration, we correlated individual differences between noncorrected and attenuation-corrected images, as well as between attenuation-corrected images before and after reregistration, with the degree of misregistration in a multivariate analysis including additional clinical variables such as sex and body weight. RESULTS: The difference in regional radiotracer uptake was significant between noncorrected and attenuation-corrected images in all 6 segments and was most pronounced in the inferior wall. On multivariate analysis, misregistration contributed significantly to changes in radiotracer distribution in the anterior (P = 0.038), septal (P = 0.011), and inferior (P = 0.006) segments. The mean misregistration was 8.6 +/- 3.8 mm (1.25 +/- 0.55 pixel). Misregistration of one or more pixels was observed in 64% of studies. Reregistration of misalignment significantly affected regional radiotracer distribution in the segments shown to be influenced by misregistration. CONCLUSION: Misregistration occurs with SPECT/CT systems and influences regional tracer distribution on attenuation-corrected myocardial images. Reregistration of misaligned studies may be a useful tool for correction. The impact of this strategy on the diagnostic and prognostic accuracy of cardiac hybrid imaging needs to be determined.

Comparison of SPECT/CT, SPECT, and planar imaging with single- and dual-phase (99m)Tc-sestamibi parathyroid scintigraphy.

UNLABELLED: Various methodologies for (99m)Tc-sestamibi parathyroid scintigraphy are in clinical use. There are few direct comparisons between the different methods and even less evidence supporting the superiority of one over another. Some reports suggest that SPECT is superior to planar imaging. The addition of CT to SPECT may further improve parathyroid adenoma localization. The purpose of our investigation was to compare hybrid SPECT/CT, SPECT, and planar imaging and to determine whether dual-phase imaging is advantageous for the 3 methodologies. METHODS: Scintigraphy was performed on 110 patients with primary hyperparathyroidism and no prior neck surgery. Of these, 98 had single adenomas and are the subject of this review. Planar imaging and SPECT/CT were performed at 15 min and 2 h after injection. Six image sets (early and delayed planar imaging, SPECT, and SPECT/CT) and combinations of the 2 image sets were reviewed for adenoma localization at 13 possible sites. Each review was scored for location and certainty of focus by 2 reviewer groups. Surgical location served as the standard. Sensitivity, specificity, area under the curve, positive predictive value, negative predictive value, and kappa-values were determined for each method. RESULTS: The overall kappa-coefficient (certainty of adenoma focus) between reading groups was 0.68 (95% confidence interval, 0.66-0.70). The highest values were for dual-phase studies that included SPECT/CT. Dual-phase planar imaging, SPECT, and SPECT/CT were statistically significantly superior to single-phase early or delayed imaging in sensitivity, area under the curve, and positive predictive value. Neither single-phase nor dual-phase SPECT was statistically superior to dual-phase planar imaging. Early-phase SPECT/CT in combination with any delayed imaging method was superior to dual-phase planar imaging or SPECT for sensitivity, area under the curve, and positive predictive value. CONCLUSION: Early SPECT/CT in combination with any delayed imaging method was statistically significantly superior to any single- or dual-phase planar or SPECT study for parathyroid adenoma localization. Localization with dual-phase acquisition was more accurate than with single-phase (99m)Tc-sestamibi scintigraphy for planar imaging, SPECT, and SPECT/CT.

Efficacy of preoperative combined 18-fluorodeoxyglucose positron emission tomography and computed tomography for assessing primary rectal cancer response to neoadjuvant therapy.

PURPOSE: Efficacy of F-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) for determining neoadjuvant therapy response in rectal cancer is not well established. We sought to evaluate serial FDG-PET/CT for assessing tumor down-staging, percentage residual tumor, and complete response or microscopic disease with rectal cancer neoadjuvant therapy. METHODS: Patients with rectal cancer undergoing neoadjuvant therapy, definitive surgical resection, and FDG-PET/CT before and 4-6 weeks after neoadjuvant treatment were included. Tumors were evaluated pretreatment and on final pathology for size and stage. FDG-PET/CT parameters assessed were visual response score (VRS), standardized uptake value (SUV), PET-derived tumor volume (PETvol), CT-derived tumor volume (CTvol), and total lesion glycolysis (delta TLG). RESULTS: Twenty-one rectal cancer patients over 3 years underwent neoadjuvant treatment, serial FDG-PET/CT, and resection. Complete response or microscopic disease (n = 7, 33%) was associated with higher Delta CTvol (AUC = 0.82, p = 0.004) and Delta SUV (AUC = 0.79, p = 0.01). Tumor down-staging (n = 14, 67%) was associated with greater Delta PETvol (AUC = 0.82, p < 0.001) and Delta SUV (AUC = 0.82, p < 0.001). Pathologic lymph node disease (n = 7, 33%) correlated with Delta CTvol (AUC = 0.75, p = 0.03) and Delta PETvol (AUC = 0.70, p = 0.08). CONCLUSION: FDG-PET/CT parameters were best for assessing tumor down-staging and percentage of residual tumor after neoadjuvant treatment of rectal cancer and can potentially assist in treatment planning.

FDG PET in the follow-up management of patients with newly diagnosed Hodgkin and non-Hodgkin lymphoma after first-line chemotherapy.

PURPOSE: The purpose of this study was to evaluate the accuracy of PET imaging for predicting recurrence of disease and determining fields of radiation therapy for patients with lymphoma after first-line chemotherapy. METHODS AND MATERIALS: The study population included 40 patients with lymphoma, newly diagnosed, staged and treated with either chemotherapy alone or combined modality therapy at this institution. PET findings were correlated with CT findings and radiation ports. Treatment and follow-up course were analyzed to determine patterns of failure. RESULTS: Twenty-eight of 40 patients (70%) were treated with chemotherapy alone, 12 of 40 (30%) were treated with combined modality therapy. Of the patients who received chemotherapy alone, 21 (75%) had a negative follow-up PET scan at the original site of disease, and 5 of these 21 (24%) recurred within the original site of disease. Of the patients who received combined modality therapy, 10 (83%) had a negative follow-up PET scan at the original site of disease and none recurred within the original site of disease. CONCLUSIONS: A negative PET scan after completion of therapy does not exclude the presence of residual microscopic disease and does not indicate complete remission. A higher recurrence rate in patients who were treated with chemotherapy alone compared with combined modality therapy suggests that some of these patients may benefit from aggressive radiation therapy planned at initial staging. The radiation treatment volumes may be better planned from the initial staging PET study because a negative follow-up PET scan after chemotherapy cannot exclude residual microscopic disease.

Prospective feasibility trial of radiotherapy target definition for head and neck cancer using 3-dimensional PET and CT imaging.

UNLABELLED: The aim of this investigation was to evaluate the influence and accuracy of (18)F-FDG PET in target volume definition as a complementary modality to CT for patients with head and neck cancer (HNC) using dedicated PET and CT scanners. METHODS: Six HNC patients were custom fitted with head and neck and upper body immobilization devices, and conventional radiotherapy CT simulation was performed together with (18)F-FDG PET imaging. Gross target volume (GTV) and pathologic nodal volumes were first defined in the conventional manner based on CT. A segmentation and surface-rendering registration technique was then used to coregister the (18)F-FDG PET and CT planning image datasets. (18)F-FDG PET GTVs were determined and displayed simultaneously with the CT contours. CT GTVs were then modified based on the PET data to form final PET/CT treatment volumes. Five-field intensity-modulated radiation therapy (IMRT) was then used to demonstrate dose targeting to the CT GTV or the PET/CT GTV. RESULTS: One patient was PET-negative after induction chemotherapy. The CT GTV was modified in all remaining patients based on (18)F-FDG PET data. The resulting PET/CT GTV was larger than the original CT volume by an average of 15%. In 5 cases, (18)F-FDG PET identified active lymph nodes that corresponded to lymph nodes contoured on CT. The pathologically enlarged CT lymph nodes were modified to create final lymph node volumes in 3 of 5 cases. In 1 of 6 patients, (18)F-FDG-avid lymph nodes were not identified as pathologic on CT. In 2 of 6 patients, registration of the independently acquired PET and CT data using segmentation and surface rendering resulted in a suboptimal alignment and, therefore, had to be repeated. Radiotherapy planning using IMRT demonstrated the capability of this technique to target anatomic or anatomic/physiologic target volumes. In this manner, metabolically active sites can be intensified to greater daily doses. CONCLUSION: Inclusion of (18)F-FDG PET data resulted in modified target volumes in radiotherapy planning for HNC. PET and CT data acquired on separate, dedicated scanners may be coregistered for therapy planning; however, dual-acquisition PET/CT systems may be considered to reduce the need for reregistrations. It is possible to use IMRT to target dose to metabolically active sites based on coregistered PET/CT data.

Phantom validation of coregistration of PET and CT for image-guided radiotherapy.

Radiotherapy treatment planning integrating positron emission tomography (PET) and computerized tomography (CT) is rapidly gaining acceptance in the clinical setting. Although hybrid systems are available, often the planning CT is acquired on a dedicated system separate from the PET scanner. A limiting factor to using PET data becomes the accuracy of the CT/PET registration. In this work, we use phantom and patient validation to demonstrate a general method for assessing the accuracy of CT/PET image registration and apply it to two multi-modality image registration programs. An IAEA (International Atomic Energy Association) brain phantom and an anthropomorphic head phantom were used. Internal volumes and externally mounted fiducial markers were filled with CT contrast and 18F-fluorodeoxyglucose (FDG). CT, PET emission, and PET transmission images were acquired and registered using two different image registration algorithms. CT/PET Fusion (GE Medical Systems, Milwaukee, WI) is commercially available and uses a semi-automated initial step followed by manual adjustment. Automatic Mutual Information-based Registration (AMIR), developed at our institution, is fully automated and exhibits no variation between repeated registrations. Registration was performed using distinct phantom structures; assessment of accuracy was determined from registration of the calculated centroids of a set of fiducial markers. By comparing structure-based registration with fiducial-based registration, target registration error (TRE) was computed at each point in a three-dimensional (3D) grid that spans the image volume. Identical methods were also applied to patient data to assess CT/PET registration accuracy. Accuracy was calculated as the mean with standard deviation of the TRE for every point in the 3D grid. Overall TRE values for the IAEA brain phantom are: CT/PET Fusion = 1.71 +/- 0.62 mm, AMIR = 1.13 +/- 0.53 mm; overall TRE values for the anthropomorphic head phantom are: CT/PET Fusion = 1.66 +/- 0.53 mm, AMIR = 1.15 +/- 0.48 mm. Precision (repeatability by a single user) measured for CT/PET Fusion: IAEA phantom = 1.59 +/- 0.67 mm and anthropomorphic head phantom = 1.63 +/- 0.52 mm. (AMIR has exact precision and so no measurements are necessary.) One sample patient demonstrated the following accuracy results: CT/PET Fusion = 3.89 +/- 1.61 mm, AMIR = 2.86 +/- 0.60 mm. Semi-automatic and automatic image registration methods may be used to facilitate incorporation of PET data into radiotherapy treatment planning in relatively rigid anatomic sites, such as head and neck. The overall accuracies in phantom and patient images are < 2 mm and < 4 mm, respectively, using either registration algorithm. Registration accuracy may decrease, however, as distance from the initial registration points (CT/PET fusion) or center of the image (AMIR) increases. Additional information provided by PET may improve dose coverage to active tumor subregions and hence tumor control. This study shows that the accuracy obtained by image registration with these two methods is well suited for image-guided radiotherapy.

Sincalide-stimulated cholescintigraphy: a multicenter investigation to determine optimal infusion methodology and gallbladder ejection fraction normal values.

UNLABELLED: Sincalide-stimulated cholescintigraphy is performed to quantify gallbladder contraction and emptying. However, different infusion methods are used for this study. Our purpose was to determine the infusion method with the least variability (smallest coefficient of variation [CV]) for calculation of the gallbladder ejection fraction (GBEF) in healthy subjects and to establish normal values. METHODS: Sixty healthy volunteers at 4 medical centers were injected intravenously with (99m)Tc-mebrofenin. After gallbladder visualization had been confirmed at 60 min, 0.02 microg of sincalide per kilogram was administered using 3 different infusion durations, 15, 30, and 60 min, each performed on separate days. The CV, mean, SD, first to 99th percentile, and fifth to 95th percentile were calculated. GBEF normal values were determined for the different infusion durations. RESULTS: The CV was smallest for the 60-min infusion at 60 min (19%; 95% confidence interval [CI], 16%-23%), compared with the 30-min infusion at 30 min (35%; 95% CI, 29.2%-42.1%) and the 15-min infusion at 15 min (52%; 95% CI, 44%-63%). These were all significantly different (P < 0.0007). For the 60-min infusion at 60 min, the lower limit of normal for the GBEF was 38% defined at the 1% CI. CONCLUSION: The GBEF at 60 min has the lowest CV in healthy subjects, compared with shorter infusions of 15 or 30 min. This multicenter trial establishes a GBEF lower limit of normal of 38% (first percentile) for a 60-min infusion of 0.02 microg of sincalide per kilogram, quantified at 60 min. Using this infusion method minimizes the variability in measured GBEFs. This sincalide infusion method should become the standard for routine clinical use.

Cold defect on bone scan in a vertebral body after percutaneous vertebroplasty.

Percutaneous vertebroplasty using bone cements is increasingly being used to stabilize osteoporotic spinal compression fractures. Although the scintigraphic appearance of compression fractures has been well-described, the post-vertebroplasty bone scan appearance has not. This case report describes a characteristic cold defect of a vertebral body after percutaneous vertebroplasty.