18F-Sodium fluoride PET/CT predicts overall survival in patients with advanced genitourinary malignancies treated with cabozantinib and nivolumab with or without ipilimumab.

PURPOSE: We evaluated the prognostic value of 18F-sodium fluoride (NaF) PET/CT in patients with urological malignancies treated with cabozantinib and nivolumab with or without ipilimumab. METHODS: We prospectively recruited patients with advanced urological malignancies into a phase I trial of cabozantinib plus nivolumab with or without ipilimumab. NaF PET/CT scans were performed pre- and 8 weeks post-treatment. We measured the total volume of fluoride avid bone (FTV) using a standardized uptake value (SUV) threshold of 10. We used Kaplan-Meier analysis to predict the overall survival (OS) of patients in terms of SUVmax, FTV, total lesion fluoride (TLF) uptake at baseline and 8 weeks post-treatment, and percent change in FTV and TLF. RESULT: Of 111 patients who underwent NaF PET/CT, 30 had bone metastases at baseline. Four of the 30 patients survived for the duration of the study period. OS ranged from 0.23 to 34 months (m) (median 6.0 m). The baseline FTV of all 30 patients ranged from 9.6 to 1570 ml (median 439 ml). The FTV 8 weeks post-treatment was 56-6296 ml (median 448 ml) from 19 available patients. Patients with higher TLF at baseline had shorter OS than patients with lower TLF (3.4 vs 14 m; p = 0.022). Patients with higher SUVmax at follow-up had shorter OS than patients with lower SUVmax (5.6 vs 24 m; p = 0.010). However, FTV and TLF 8 weeks post-treatment did not show a significant difference between groups (5.6 vs 17 m; p = 0.49), and the percent changes in FTV (12 vs 14 m; p = 0.49) and TLF (5.6 vs 17 m; p = 0.54) also were not significant. CONCLUSION: Higher TLF at baseline and higher SUVmax at follow-up NaF PET/CT corresponded with shorter survival in patients with bone metastases from urological malignancies who underwent treatment. NaF PET/CT may be a useful predictor of OS in this population.

Time-of-Flight PET/CT Imaging of Ga-68-Dotatate: Normal Pattern, SUV Quantification, and Differences from Non-Time-of-Flight Imaging.

Purpose The biodistribution of gallium-68-dotatate (Ga-68-dotatate) and standardized uptake values (SUVs) using non-time-of-flight (TOF) positron emission tomography/computed tomography (PET/CT) cameras is well established. However, with the eventual retirement of older PET cameras and their replacement with newer, highly sensitive TOF PET/CT cameras, where SUV max measurements are reportedly higher, updated knowledge of normal SUV max range is needed and, to our knowledge, not previously reported. Our objectives are as follows: To establish normal Ga-68-dotatate TOF SUV max database for common structures and to aid the visual detection of abnormalities objectively. To compare SUV max values using the TOF and non-TOF algorithms. Methods Fifty consecutive patients referred routinely to our nuclear medicine service (20 men, 30 women; median age 55 years) with presumed neuroendocrine tumors underwent Ga-68-dotatate scans on a PET-CT camera having capability of reconstructing both TOF/non-TOF images. Region of interests (ROIs) were drawn around 24 normal structures as well as the primary lesion with abnormal radiotracer uptake and SUV max was measured. The same ROI was analyzed using both algorithms simultaneously and both TOF and non-TOF SUV max values were compared. Results Twelve hundred ROIs were evaluated. Non-TOF Ga-68-dotatate uptake in normal structures was in alignment with previously published studies. As compared to non-TOF, TOF images had better target to background ratios visually. TOF SUV max was higher for all structures except for lung and brain. TOF SUV max was more than double in adrenals/uncinate process of the pancreas; approximately 1.8 times in abnormal lesions, lymph nodes, pineal gland; and greater than 1.5 times in thyroid, breast, and pancreatic head. Conclusion Normal database of Ga-68-dotatate TOF SUV max is provided for common structures to aid visual detection of abnormalities objectively. Overall, TOF SUV max measures higher in identical ROIs, with abnormal lesions measuring approximately 1.8 times higher versus non-TOF technology. These findings need to be taken in consideration when comparing patient scans imaged on different PET/CT technologies.

18F-DCFPyL PET/CT Imaging in Patients with Biochemically Recurrent Prostate Cancer After Primary Local Therapy.

Our objective was to investigate the lesion detection rate of 18F-DCFPyL PET/CT, a prostate-specific membrane antigen (PSMA)-targeted PET agent, in patients with biochemically relapsed prostate cancer after primary local therapy. Methods: This was a prospective institutional review board-approved study of 90 patients with documented biochemical recurrence (median prostate-specific antigen [PSA], 2.5 ng/mL; range, 0.21-35.5 ng/mL) and negative results on conventional imaging after primary local therapies, including radical prostatectomy (n = 38), radiation (n = 27), or a combination of the two (n = 25). Patients on androgen deprivation therapy were excluded. Patients underwent whole-body 18F-DCFPyL PET/CT (299.9 ± 15.5 MBq) at 2 h after injection. The PSMA PET lesion detection rate was correlated with PSA, PSA kinetics, and original primary tumor grade. Results: Seventy patients (77.8%) showed positive PSMA PET results, with a total of 287 lesions identified: 37 prostate bed foci, 208 lesions in lymph nodes, and 42 in distant sites in bones or organs, Eleven patients had negative results, and 9 patients showed indeterminate lesions, which were considered negative in this study. The detection rates were 47.6% (n = 10/21), 50% (n = 5/10), 88.9% (n = 8/9), and 94% (n = 47/50) for PSA levels of >0.2 to <0.5, 0.5 to <1.0, 1 to <2.0, and ≥2.0 ng/mL, respectively. In postsurgical patients, PSA, PSA doubling time, and PSA velocity correlated with PET results, but the same was not true for postradiation patients. These parameters also correlated with the extent of disease on PET (intrapelvic vs. extrapelvic). There was no significant difference in the rate of positive scans between patients with higher-grade and lower-grade primary tumors (Gleason score of ≥4 + 3 vs. <3 + 4). Tumor recurrence was histology-confirmed in 40% (28/70) of patients. On a per-patient basis, positive predictive value was 93.3% (95% confidence interval, 77.6%-99.2%) by histopathologic validation and 96.2% (95% confidence interval, 86.3%-99.7%) by the combination of histology and imaging/clinical follow-up. Conclusion:18F-DCFPyL PET/CT imaging offers high detection rates in biochemically recurrent prostate cancer patients and is positive in about 50% of patients with a PSA level of less than 0.5 ng/mL, which could substantially impact clinical management. In postsurgical patients, 18F-DCFPyL PET/CT correlates with PSA, PSA doubling time, and PSA velocity, suggesting it may have prognostic value. 18F-DCFPyL PET/CT is highly promising for localizing sites of recurrent prostate cancer.

A pilot study of the value of 18F-fluoro-deoxy-thymidine PET/CT in predicting viable lymphoma in residual 18F-FDG avid masses after completion of therapy.

BACKGROUND: Despite its success in diagnosing and staging lymphoma, F-FDG PET/CT can be falsely positive in areas of posttreatment inflammation. 3'-F-fluoro-3'-deoxy-l-thymidine (F-FLT) is a structural analog of the DNA constituent thymidine; its uptake correlates with cellular proliferation. This pilot study evaluates the ability of F-FLT PET/CT to distinguish viable lymphoma from posttreatment inflammatory changes in F-FDG avid residual masses. METHODS: Twenty-one patients with lymphoma with at least 1 F-FDG avid residual mass after therapy underwent F-FLT PET/CT imaging. F-FDG and F-FLT uptake values were compared, including quantitative pharmacokinetic parameters extracted from the F-FLT time activity curves generated from dynamic data using graphical and nonlinear compartmental modeling. RESULTS: The true nature of the residual mass was confirmed by biopsy in 12 patients (8 positive and 4 negative for viable lymphoma and by follow-up CT and/or repeat F-FDG PET/CT imaging over 1 year); among the remaining 9 patients, 7 lesions resolved or decreased and 2 showed growth indicative of lymphoma. F-FLT PET SUVest.max was significantly higher in tumors than in benign lesions (5.5 [2.2] vs 1.7 [0.6]; P < 0.0001), whereas the difference in F-FDG SUVs was not significant (malignant, 7.8 [3.8] vs benign, 5.4 [2.4]; P = 0.11). All of the benign lesions had an F-FLT SUVest.max of less than 3.0. CONCLUSIONS: F-FLT shows improved specificity over F-FDG in distinguishing residual lymphoma from posttreatment inflammation and may be useful in the evaluation of patients with residual F-FDG-positive masses after completing therapy.