A Pilot Study of Dynamic 18F-DCFPyL PET/CT Imaging of Prostate Adenocarcinoma in High-Risk Primary Prostate Cancer Patients.

PURPOSE: The primary aim of this study was to investigate the pharmacokinetics of 18F-DCFPyL, an 18F-labeled PSMA-based ligand, and to explore the utility of early time point positron emission tomography (PET) imaging extracted from PET data to distinguish malignant primary prostate from benign prostate tissue. PROCEDURES: Ten consecutive patients with biopsy-proven high-risk prostate cancer underwent a dynamic 18F-DCFPyL PET/CT scan of the pelvis for the first 45 min post-injection (p.i.) followed by a static PET/CT at 2 h p.i. 18F-DCFPyL uptake values and kinetics were compared between benign prostate tissue and prostate cancer, including quantitative pharmacokinetic PET parameters extracted from 18F-DCFPyL time activity curves generated from dynamic data using a two-tissue compartment model and Patlak plots. RESULTS: 18F-DCFPyL uptake values were significantly higher in primary prostate tumors than those in benign prostatic hyperplasia (BPH) and normal prostate tissue at 5 min, 30 min, and 120 min p.i. (P = 0.0002), when examining both SUVmax and SUVmean values. The two-tissue compartment model found an overall influx value (Ki) of 0.063 in primary prostate cancer, demonstrating a Ki over 15-fold higher in malignant prostate tissue compared with BPH (Ki = 0.004) and normal prostate tissue (Ki = 0.005) (P = 0.0001). CONCLUSION: High-risk primary prostate cancer is readily identified on dynamic and static, delayed, 18F-DCFPyL PET images. The tumor-to-background ratio increases over time, with optimal 18F-DCFPyL PET/CT imaging at 120 min p.i. for evaluation of prostate cancer, but not necessarily ideal for clinical application. Primary prostate cancer demonstrates different uptake kinetics in comparison to BPH and normal prostate tissue. The 15-fold difference in Ki between prostate cancer and non-cancer (BPH and normal) tissues translates to an ability to distinguish prostate cancer from normal tissue at time points as early as 5 to 10 min p.i.

Predictors of 18F-DCFPyL PET/CT Positivity in Patients with Biochemical Recurrence of Prostate Cancer After Local Therapy.

Our objective was to investigate the factors predicting scan positivity and disease location in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after primary local therapy using prostate-specific membrane antigen-targeted 18F-DCFPyL PET/CT. Methods: This was a 2-institution study including 245 BCR PCa patients after primary local therapy and negative results on conventional imaging. The patients underwent 18F-DCFPyL PET/CT. We tested for correlations of lesion detection rate and disease location with tumor characteristics, time from initial therapy, prostate-specific antigen (PSA) level, and PSA doubling time (PSAdt). Multivariate logistic regression analyses were used to determine predictors of a positive scan. Regression-based coefficients were used to develop nomograms predicting scan positivity and extrapelvic disease. Results: Overall, 79.2% (194/245) of patients had a positive 18F-DCFPyL PET/CT result, with detection rates of 48.2% (27/56), 74.3% (26/35), 84% (37/44), 96.7% (59/61), and 91.8% (45/49) for PSAs of <0.5, 0.5 to <1.0, 1.0 to <2.0, 2.0 to <5.0, and ≥5.0 ng/mL, respectively. Patients with lesions confined to the pelvis had lower PSAs than those with distant sites (1.6 ± 3.5 vs. 3.0 ± 6.3 ng/mL, P < 0.001). In patients treated with prostatectomy (n = 195), 24.1% (47/195) had a negative scan result, 46.1% (90/195) showed intrapelvic disease, and 29.7% (58/195) showed extrapelvic disease. In the postradiation subgroup (n = 50), 18F-DCFPyL PET/CT was always negative at a PSA lower than 1.0 ng/mL and extrapelvic disease was seen only when PSA was greater than 2.0 ng/mL. At multivariate analysis, PSA and PSAdt were independent predictive factors of scan positivity and the presence of extrapelvic disease in postsurgical patients, with area under the curve of 78% and 76%, respectively. PSA and PSAdt were independent predictors of the presence of extrapelvic disease in the postradiation cohort, with area under the curve of 85%. Time from treatment to scan was significantly longer for prostatectomy-bed-only recurrences than for those with bone or visceral disease (6.2 ± 6.4 vs. 2.4 ± 1.3 y, P < 0.001). Conclusion:18F-DCFPyL PET/CT offers high detection rates in BCR PCa patients. PSA and PSAdt are able to predict scan positivity and disease location. Furthermore, the presence of bone or visceral lesions is associated with shorter intervals from treatment than are prostate-bed-only recurrences. These tools might guide clinicians to select the most suitable candidates for 18F-DCFPyL PET/CT imaging.

Evaluating Biochemically Recurrent Prostate Cancer: Histologic Validation of 18F-DCFPyL PET/CT with Comparison to Multiparametric MRI.

Background Prostate cancer recurrence is found in up to 40% of men with prior definitive (total prostatectomy or whole-prostate radiation) treatment. Prostate-specific membrane antigen PET agents such as 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) may improve detection of recurrence compared with multiparametric MRI; however, histopathologic validation is lacking. Purpose To determine the sensitivity, specificity, and positive predictive value (PPV) of 18F-DCFPyL PET/CT based on histologic analysis and to compare with pelvic multiparametric MRI in men with biochemically recurrent prostate cancer. Materials and Methods Men were prospectively recruited after prostatectomy and/or radiation therapy with rising prostate-specific antigen level (median, 2.27 ng/mL; range, 0.2-27.45 ng/mL) and a negative result at conventional imaging (bone scan and/or CT). Participants underwent 18F-DCFPyL PET/CT imaging and 3.0-T pelvic multiparametric MRI. Statistical analysis included Wald and modified χ2 tests. Results A total of 323 lesions were visualized in 77 men by using 18F-DCFPyL or multiparametric MRI, with imaging detection concordance of 25% (82 of 323) when including all lesions in the MRI field of view and 53% (52 of 99) when only assessing prostate bed lesions. 18F-DCFPyL depicted more pelvic lymph nodes than did MRI (128 vs 23 nodes). Histologic validation was obtained in 80 locations with sensitivity, specificity, and PPV of 69% (25 of 36; 95% confidence interval [CI]: 51%, 88%), 91% (40 of 44; 95% CI: 74%, 98%), and 86% (25 of 29; 95% CI: 73%, 97%) for 18F-DCFPyL and 69% (24 of 35; 95% CI: 50%, 86%), 74% (31 of 42; 95% CI: 42%, 89%), and 69% (24 of 35; 95% CI: 50%, 88%) for multiparametric MRI (P = .95, P = .14, and P = .07, respectively). In the prostate bed, sensitivity, specificity, and PPV were 57% (13 of 23; 95% CI: 32%, 81%), 86% (18 of 21; 95% CI: 73%, 100%), and 81% (13 of 16; 95% CI: 59%, 100%) for 18F-DCFPyL and 83% (19 of 23; 95% CI: 59%, 100%), 52% (11 of 21; 95% CI: 29%, 74%), and 66% (19 of 29; 95% CI: 44%, 86%) for multiparametric MRI (P = .19, P = .02, and P = .17, respectively). The addition of 18F-DCFPyL to multiparametric MRI improved PPV by 38% overall (P = .02) and by 30% (P = .09) in the prostate bed. Conclusion Findings with 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) were histologically validated and demonstrated high specificity and positive predictive value. In the pelvis, 18F-DCFPyL depicted more lymph nodes and improved positive predictive value and specificity when added to multiparametric MRI. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Zukotynski and Rowe in this issue.

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.

Near-infrared photoimmunotherapy through bone.

Near-infrared photoimmunotherapy (NIR-PIT) is a molecularly targeted cancer phototherapy that is based on injecting a conjugate of a silicon-phthalocyanine derivative, IRdye 700DX (IR700), and a monoclonal antibody that targets an expressed antigen on the cancer cell surface. Subsequent local exposure to NIR light results in the rapid and highly selective immunogenic cell death of targeted cancer cells. Because many cancers grow in bones through which light does not penetrate well, the goal of this study was to determine if NIR-PIT can effectively treat cancers in bone. A bovine rib was used as a bone sample. Because the sample's NIR light transmittance was shown to be approximately 4.52% in preliminary tests, it was hypothesized that a maximum radiation dosage of 128 and 1500 J/cm2 would be sufficient to induce cell death in in vitro target cells and in vivo mouse tumor models, respectively. Cell viability was measured through bioluminescence studies comparing relative luciferase activity, as well as a cytotoxicity assay. In the in vitro model, tumor cell viability was significantly decreased after 64 and 128 J/cm2 NIR light irradiation through the bone. An in vivo mouse tumor model also showed that 1500 J/cm2 NIR light irradiation through the bone significantly reduced tumor viability at both 24 and 48 hours posttreatment compared to the control group (P = .026 and .040 respectively). Therefore, despite limitations in light transmission, NIR-PIT nevertheless is capable of effectively treating cancers within bone.

Clinical impact of PSMA-based 18F-DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy.

PURPOSE: The purpose of our study was to assess 18F-DCFBC PET/CT, a PSMA targeted PET agent, for lesion detection and clinical management of biochemical relapse in prostate cancer patients after primary treatment. METHODS: This is a prospective IRB-approved study of 68 patients with documented biochemical recurrence after primary local therapy consisting of radical prostatectomy (n = 50), post radiation therapy (n = 9) or both (n = 9), with negative conventional imaging. All 68 patients underwent whole-body 18F-DCFBC PET/CT, and 62 also underwent mpMRI within one month. Lesion detection with 18F-DCFBC was correlated with mpMRI findings and pre-scan PSA levels. The impact of 18F-DCFBC PET/CT on clinical management and treatment decisions was established after 6 months' patient clinical follow-up. RESULTS: Forty-one patients (60.3%) showed at least one positive 18F-DCFBC lesion, for a total of 79 lesions, 30 in the prostate bed, 39 in lymph nodes, and ten in distant sites. Tumor recurrence was confirmed by either biopsy (13/41 pts), serial CT/MRI (8/41) or clinical follow-up (15/41); there was no confirmation in five patients, who continue to be observed. The 18F-DCFBC and mpMRI findings were concordant in 39 lesions (49.4%), and discordant in 40 lesions (50.6%); the majority (n = 32/40) of the latter occurring because the recurrence was located outside the mpMRI field of view. 18F-DCFBC PET positivity rates correlated with PSA values and 15%, 46%, 83%, and 77% were seen in patients with PSA values <0.5, 0.5 to <1.0, 1.0 to <2.0, and ≥2.0 ng/mL, respectively. The optimal cut-off PSA value to predict a positive 18F-DCFBC scan was 0.78 ng/mL (AUC = 0.764). A change in clinical management occurred in 51.2% (21/41) of patients with a positive 18F-DCFBC result, generally characterized by starting a new treatment in 19 patients or changing the treatment plan in two patients. CONCLUSIONS: 18F-DCFBC detects recurrences in 60.3% of a population of patients with biochemical recurrence, but results are dependent on PSA levels. Above a threshold PSA value of 0.78 ng/mL, 18F-DCFBC was able to identify recurrence with high reliability. Positive 18F-DCFBC PET imaging led clinicians to change treatment strategy in 51.2% of patients.

18F-DCFBC Prostate-Specific Membrane Antigen-Targeted PET/CT Imaging in Localized Prostate Cancer: Correlation With Multiparametric MRI and Histopathology.

PURPOSE: To assess the ability of (N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-F-fluorobenzyl-L-cysteine) (F-DCFBC), a prostate-specific membrane antigen-targeted PET agent, to detect localized prostate cancer lesions in correlation with multiparametric MRI (mpMRI) and histopathology. METHODS: This Health Insurance Portability and Accountability Act of 1996-compliant, prospective, institutional review board-approved study included 13 evaluable patients with localized prostate cancer (median age, 62.8 years [range, 51-74 years]; median prostate-specific antigen, 37.5 ng/dL [range, 3.26-216 ng/dL]). Patients underwent mpMRI and F-DCFBC PET/CT within a 3 months' window. Lesions seen on mpMRI were biopsied under transrectal ultrasound/MRI fusion-guided biopsy, or a radical prostatectomy was performed. F-DCFBC PET/CT and mpMRI were evaluated blinded and separately for tumor detection on a lesion basis. For PET image analysis, MRI and F-DCFBC PET images were fused by using software registration; imaging findings were correlated with histology, and uptake of F-DCFBC in tumors was compared with uptake in benign prostatic hyperplasia nodules and normal peripheral zone tissue using the 80% threshold SUVmax. RESULTS: A total of 25 tumor foci (mean size, 1.8 cm; median size, 1.5 cm; range, 0.6-4.7 cm) were histopathologically identified in 13 patients. Sensitivity rates of F-DCFBC PET/CT and mpMRI were 36% and 96%, respectively, for all tumors. For index lesions, the largest tumor with highest Gleason score, sensitivity rates of F-DCFBC PET/CT and mpMRI were 61.5% and 92%, respectively. The average SUVmax for primary prostate cancer was higher (5.8 ± 4.4) than that of benign prostatic hyperplasia nodules (2.1 ± 0.3) or that of normal prostate tissue (2.1 ± 0.4) at 1 hour postinjection (P = 0.0033). CONCLUSIONS: The majority of index prostate cancers are detected with F-DCFBC PET/CT, and this may be a prognostic indicator based on uptake and staging. However, for detecting prostate cancer with high sensitivity, it is important to combine prostate-specific membrane antigen PET/CT with mpMRI.

PET/CT imaging of renal cell carcinoma with (18)F-VM4-037: a phase II pilot study.

BACKGROUND: Carbonic anhydrase IX (CA-IX) is a potential imaging biomarker of clear cell renal cell carcinoma (ccRCC). Here, we report the results of a phase II clinical trial of a small molecule radiotracer targeting CA-IX ((18)F-VM4-037) in ccRCC. METHODS: Between October 2012 and May 2013, 11 patients with kidney masses underwent (18)F-VM4-037 PET/CT prior to surgery. Dynamic imaging was performed for the first 45 min post injection and whole-body imaging was obtained at 60 min post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging. RESULTS: All patients tolerated the radiotracer well with no adverse events. Ten of the 11 patients had histologically confirmed malignancy. One patient had a Bosniak Type 3 cyst with no tumor found at surgery. Two patients had extrarenal disease and 9 had tumors only in the kidney. Primary ccRCC lesions were difficult to visualize on PET alone due to high uptake of the tracer in the adjacent normal kidney parenchyma, however when viewed in conjunction with CT, the tumors were easily localized. Metastatic lesions were clearly visible on PET. Mean SUV for primary kidney lesions was 2.55 in all patients; in patients with histologically confirmed ccRCC, the mean SUV was 3.16. The time-activity curves (TAC) are consistent with reversible ligand binding with peak activity concentration at 8 min post injection followed by washout. Distribution Volume Ratio (DVR) of the lesions was measured using the Logan graphical analysis method. The mean DVR value across the 9 kidney lesions was 5.2 ± 2.8, (range 0.68-10.34). CONCLUSION: 18F-VM4-037 is a well-tolerated PET agent that allows same day imaging of CA-IX expression. The agent demonstrated moderate signal uptake in primary tumors and excellent visualization of CA-IX positive metastases. While the evaluation of primary ccRCC lesions is challenging due to high background activity in the normal kidney parenchyma, 18F-VM4-037 may be most useful in the evaluation of metastatic ccRCC lesions.

11C-Acetate PET/CT in localized prostate cancer: a study with MRI and histopathologic correlation.

UNLABELLED: This work characterizes the uptake of (11)C-acetate in prostate cancer (PCa), benign prostate hyperplasia, and normal prostate tissue in comparison with multiparametric MRI, whole-mount histopathology, and clinical markers to evaluate the potential utility of (11)C-acetate for delineating intraprostatic tumors in a population of patients with localized PCa. METHODS: Thirty-nine men with presumed localized PCa underwent dynamic-static abdominal-pelvic (11)C-acetate PET/CT for 30 min and 3-T multiparametric MRI before prostatectomy. PET/CT images were registered to MR images using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient-specific mold resulting in improved registration between the MRI, PET, and pathology. (11)C-acetate PET standardized uptake values were compared with multiparametric MRI and pathology. RESULTS: (11)C-acetate uptake was rapid but reversible, peaking at 3-5 min after injection and reaching a relative plateau at approximately 10 min. The average maximum standardized uptake value (10-12 min) of tumors was significantly higher than that of normal prostate tissue (4.4 ± 2.05 [range, 1.8-9.2] vs. 2.1 ± 0.94 [range, 0.7-3.4], respectively; P < 0.001); however, it was not significantly different from that of benign prostatic hyperplasia (4.8 ± 2.01 [range, 1.8-8.8]). A sector-based comparison with histopathology, including all tumors greater than 0.5 cm, revealed a sensitivity and specificity of 61.6% and 80.0%, respectively, for (11)C-acetate PET/CT and 82.3% and 95.1%, respectively, for MRI. The (11)C-acetate accuracy was comparable to that of MRI when only tumors greater than 0.9 cm were considered. In a small cohort (n = 9), (11)C-acetate uptake was independent of fatty acid synthase expression using immunohistochemistry. CONCLUSION: (11)C-acetate PET/CT demonstrates higher uptake in tumor foci than in normal prostate tissue; however, (11)C-acetate uptake in tumors is similar to that in benign prostate hyperplasia nodules. Although (11)C-acetate PET/CT is not likely to have utility as an independent modality for evaluation of localized PCa, the high uptake in tumors may make it useful for monitoring focal therapy when tissue damage after therapy may limit anatomic imaging methods.