Soft Tissue Response on 18F-Fluorocholine PET/CT in Metastatic Castrate-Resistant Prostate Cancer Treated With 223Ra-Dichloride: A Possible Abscopal Effect?

Two patients with castrate-resistant prostate cancer and symptomatic skeletal metastases underwent F-fluorocholine PET/CT prior to treatment with Ra-dichloride to reveal additional active lesions in the prostate gland and lymph nodes. Subsequent scans performed at the midpoint and end of Ra-dichloride therapy showed resolution of this soft tissue activity alongside declining bone lesion activity. Concomitant increases in plasma interleukin 6 were detected, suggesting that immune system activation may have mediated the soft tissue response. Abscopal effects usually encountered with external beam radiotherapy may also be occurring with Ra-dichloride therapy.

Prediction of PSA Progression in Castration-Resistant Prostate Cancer Based on Treatment-Associated Change in Tumor Burden Quantified by 18F-Fluorocholine PET/CT.

UNLABELLED: Measurements of metabolically active tumor volume (MATV) can be applied to (18)F-fluorocholine PET/CT to quantify whole-body tumor burden. This study evaluated the serial application of these measurements as systemic treatment response markers and predictors of disease progression in patients with castration-resistant prostate cancer (CRPC). METHODS: Forty-two patients completed sequential (18)F-fluorocholine PET/CT scans before and 1-3 mo after starting treatment for CRPC. Whole-body tumor segmentation was applied to determine net MATV from each scan. Changes in net MATV were evaluated as predictors of time to prostate-specific antigen (PSA) progression by Kaplan-Meier and proportional hazards regression analysis. RESULTS: Treatments consisted of chemotherapy in 16 patients, antiandrogens in 19 patients, (223)Ra-dichloride in 5 patients, and sipuleucel-T in 2 patients. A significant MATV response (defined as a ≥30% decrease in net MATV) was observed in 20 patients on the basis of in-treatment PET/CT performed an average of 51 d (median, 49 d) into treatment. Significantly longer times to PSA progression were observed in patients who exhibited an MATV response (418 d vs. 116 d, P = 0.0067). MATV response was associated with a hazard ratio of 0.246 (P = 0.0113) for PSA progression, which remained significant when adjusted for treatment type. CONCLUSION: Significant changes in whole-body tumor burden can be measured on (18)F-fluorocholine PET/CT over the course of contemporary treatments for CRPC. In this study, these changes were found to be predictive of PSA progression as a potential surrogate marker of treatment outcome. Because (18)F-fluorocholine PET/CT can also be used for localizing resistant tumors, this modality can potentially complement other measures of response in the precision management of advanced prostate cancer.

Prognosis Related to Metastatic Burden Measured by ¹8F-Fluorocholine PET/CT in Castration-Resistant Prostate Cancer.

UNLABELLED: This study investigated the prognostic significance of metabolically active tumor volume (MATV) measurements applied to (18)F-fluorocholine PET/CT in castration-resistant prostate cancer (CRPC). METHODS: (18)F-fluorocholine PET/CT imaging was performed on 30 patients with CRPC. Metastatic disease was quantified on the basis of maximum standardized uptake value (SUV(max)), MATV, and total lesion activity (TLA = MATV × mean standardized uptake value). Tumor burden indices derived from whole-body summation of PET tumor volume measurements (i.e., net MATV and net TLA) were evaluated as variables in Cox regression and Kaplan-Meier survival analyses. RESULTS: Net MATV ranged from 0.12 cm(3) to 1,543.9 cm(3) (median, 52.6 cm(3)). Net TLA ranged from 0.40 to 6,688.7 g (median, 225.1 g). Prostate-specific antigen level at the time of PET correlated significantly with net MATV (Pearson r = 0.65, P = 0.0001) and net TLA (r = 0.60, P = 0.0005) but not highest lesional SUV(max) of each scan. Survivors were followed for a median 23 mo (range, 6-38 mo). On Cox regression analyses, overall survival had a significant association with net MATV (P = 0.0068), net TLA (P = 0.0072), and highest lesion SUV(max) (P = 0.0173) and a borderline association with prostate-specific antigen level (P = 0.0458). Only net MATV and net TLA remained significant in univariate-adjusted survival analyses. Kaplan-Meier analysis demonstrated significant differences in survival between groups stratified by median net MATV (log-rank P = 0.0371), net TLA (log-rank P = 0.0371), and highest lesion SUV(max) (log-rank P = 0.0223). CONCLUSION: Metastatic prostate cancer detected by (18)F-fluorocholine PET/CT can be quantified on the basis of volumetric measurements of tumor metabolic activity. The prognostic value of (18)F-fluorocholine PET/CT may stem from this capacity to assess whole-body tumor burden. With further clinical validation, (18)F-fluorocholine PET-based indices of global disease activity and mortality risk could prove useful in patient-individualized treatment of CRPC.

Detection of recurrent prostate cancer with 18F-fluorocholine PET/CT in relation to PSA level at the time of imaging.

PURPOSE: To evaluate fluorine-18 fluorocholine (FCH) PET/CT for the detection of recurrent prostate cancer in relation to prostate-specific antigen (PSA) level. METHODS: FCH PET/CT was performed in 50 patients with rising PSA levels at follow-up of primary treatment of prostate cancer (radical prostatectomy in 28, radiation therapy in 13, and brachytherapy in 9). PET detection rates were determined at various PSA thresholds and examined by receiver operating characteristic analysis. RESULTS: Findings consistent with recurrent prostate cancer were noted on FCH PET/CT in 31/50 (62%) patients, with positive findings in 17/18 (94%), and 11/13 (85%), 2/7 (29%), and 1/12 (8%) patients with PSA >4, >2-4, >0.5-2, and ≤0.5 ng/mL, respectively. These findings were indicative of local/regional recurrence in 23 cases and systemic recurrence in 8 cases, with only a single route of recurrence (i.e., either hematogenous, lymphatic, or intraprostatic) in 84% of PET scans with positive findings. Abnormal tumor activity was detected in 88% of patients with a PSA level of 1.1 ng/mL or higher, and in only 6% of patients with a PSA level below this threshold value. CONCLUSION: FCH PET/CT may serve to identify the route of tumor progression in patients with recurrent prostate cancer; however, the likelihood of tumor detection may be related to the PSA level at the time of imaging.

(18)F-Choline PET/CT imaging of RECIST measurable lesions in hormone refractory prostate cancer.

PURPOSE: Apply measurability criteria based on the response evaluation criteria in solid tumors (RECIST) to lesions found on (18)F-choline positron emission tomography (PET)/computerized tomography (CT) in patients with hormone refractory prostate cancer. METHODS: Whole-body PET followed by CT or in-line PET/CT using 3.3-4 MBq/kg of (18)F-choline was performed prospectively on 30 patients with prostate cancer, castrate testosterone levels, and rising post-treatment prostate specific antigen (PSA) levels. Lesions demonstrating increased (18)F-choline uptake were classified as measurable or non-measureable based on RECIST. RESULTS: Three patients were known previously to have RECIST measurable lesions, 10 patients had metastatic findings on radionuclide bone scan, and 17 patients had elevated serum PSA level as the only evidence of disease. Lesions demonstrating increased (18)F-choline uptake were found in 28 (93%) patients. Thirty-eight PET/CT lesions from 14 patients were measurable by RECIST. Lymph node maximum standardized uptake value (SUV(max)) correlated with lymph node diameter (Pearson r = 0.44, p < 0. 001). RECIST measurable lymph node SUV(max) was significantly higher than that of non-measurable nodes (8.1 vs. 3.7, p < 0.0001). Detection of skeletal, prostatic, or RECIST-compatible lesions was more likely with a PSA level greater than 4.0 ng/ml (Fisher exact p = 0.0005). CONCLUSION: Lesions detected with (18)F-choline PET/CT are frequently measurable by RECIST at baseline. Therefore, it may be feasible to include comparisons to RECIST in evaluations of (18)F-choline as a therapeutic response marker for hormone refractory prostate cancer.

Use of step-section histopathology to evaluate 18F-fluorocholine PET sextant localization of prostate cancer.

To assess positron emission tomography (PET) with fluorine-18 fluorocholine for sextant localization of malignant prostate tumors. Histopathologic analysis was performed on step-sectioned whole-mounted prostate specimens from 15 patients who underwent PET with fluorocholine prior to radical prostatectomy. The maximum standardized uptake value (SUVmax) corresponding to prostate sextants on PET was measured by region of interest analysis and compared with histopathologic results. Histopathology demonstrated malignant involvement in 61 of 90 prostate sextants. The mean total tumor volume per specimen was 4.9 mL (range 0.01-28.7 mL). Mean SUVmax was 6.0+/-2.0 in malignant sextants and 3.8+/-1.4 in benign sextants (p<.0001). The area under the receiver operating characteristic curve was 0.82 for sextant detection of malignancy based on SUVmax measurement. Tumor diameter directly correlated with sextant SUVmax in malignant sextants (r=.54, p<.05). In 13 subjects, the largest tumor in the specimen corresponded to the sextant with the highest SUVmax. Fluorocholine PET can serve to localize dominant areas of malignancy in patients with prostate cancer. However, PET with fluorocholine may fail to identify sextants with smaller volumes of malignancy.

Cancer imaging with fluorine-18-labeled choline derivatives.

The choline transporter and choline kinase enzyme frequently are overexpressed in malignancy. Therefore, positron-emitter-labeled compounds derived from choline have the potential to serve as oncologic probes for positron emission tomography. The fluorine-18 ((18)F)-labeled choline derivative fluorocholine (FCH) in particular has demonstrated potential utility for imaging of a variety of neoplasms, including those of the breast, prostate, liver, and brain. The pharmacokinetics of FCH and other choline tracers allow for whole-body imaging within minutes of injection while still achieving high tumor-to-background contrast in most organs, including the brain. These features, along with the possibility of imaging malignancies that have proved elusive with the use of (18)F-fluorodeoxyglucose positron emission tomography support further clinical investigations of (18)F-labeled choline tracers.

Solitary brain lesions enhancing at MR imaging: evaluation with fluorine 18 fluorocholine PET.

PURPOSE: To prospectively determine whether differences between benign and malignant brain lesions can be depicted with fluorine 18 ((18)F) fluorocholine positron emission tomography (PET). MATERIALS AND METHODS: Thirty consecutive patients (14 women, 16 men; age range, 26-79 years) with solitary brain lesions that were enhanced at magnetic resonance (MR) imaging underwent whole-brain (18)F-fluorocholine PET after giving informed consent in this institutional review board-approved, HIPAA-compliant study. Histopathologic diagnoses were made in 24 cases (13 high-grade gliomas, eight metastases to the brain, and three benign lesions). In six cases, benign lesions were diagnosed on the basis of longitudinal follow-up MR findings. The maximum standardized uptake value (SUV(max)) for lesion and peritumoral regions was measured on PET images, and a lesion-to-normal tissue uptake ratio (LNR) was calculated. Differences were assessed with one-way analysis of variance, Fisher exact, and Student t tests. RESULTS: Differences in SUV(max) between high-grade gliomas (1.89 +/- 0.78 [mean +/- standard deviation]), metastases (4.11 +/- 1.68), and benign lesions (0.59 +/- 0.31) were significant (P < .0001). LNRs also differed significantly (5.15 +/- 2.51, 10.91 +/- 2.14, and 1.28 +/- 0.32, respectively; P < .0001). These differences were also significant at pairwise analysis. The peritumoral LNR exceeded 2.0 in seven high-grade gliomas and no metastases (P = .02). In 14 radiation-treated patients, the lesions classified as benign demonstrated significantly less uptake compared with the recurrent tumors (SUV(max): 0.72 +/- 0.38 vs 2.27 +/- 1.24, P < .01; LNR: 1.36 +/- 0.43 vs 5.88 +/- 3.66, P < .01). CONCLUSION: High-grade gliomas, metastases, and benign lesions can be distinguished on the basis of measured fluorocholine uptake. Increased peritumoral fluorocholine uptake is a distinguishing characteristic of high-grade gliomas.

Localization of primary prostate cancer with dual-phase 18F-fluorocholine PET.

UNLABELLED: This study compared 18F-fluorocholine uptake in malignant and benign areas of the prostate at 2 time points to determine the suitability of delayed or dual-phase 18F-fluorocholine PET for localizing malignancy in the prostate gland. METHODS: Twenty-six men (15 newly diagnosed with prostate cancer, 2 with recurrent prostate cancer, 6 with no evidence of prostate cancer recurrence after treatment, and 3 with no history of prostate cancer) underwent dual-phase PET consisting of initial whole-body PET starting 7 min after injection of 3.3-4 MBq/kg of 18F-fluorocholine followed by 1-h delayed PET of the pelvis. Tracer uptake in the prostate on the initial and delayed images was measured on a sextant basis. Prostate biopsy or whole-prostate histologic examination after radical prostatectomy was used to classify a prostate sextant as a dominant malignant region or probable benign region. For each sextant, a retention index based on the measured maximum standardized uptake value (SUVmax) was calculated on the initial and delayed images. In 15 prostates with both benign and malignant sextants on histologic examination, a malignant-to-benign ratio of SUVmax was also calculated for each time point. RESULTS: A dominant malignant region was found in 17 subjects, and a probable benign region was found in 24 subjects. The mean SUVmax for dominant malignant regions increased significantly between initial and delayed scans, from 7.6 to 8.6 (mean retention index, +14%; 95% confidence interval, 6%-22%; P = 0.002). The mean SUVmax for probable benign regions decreased significantly between initial and delayed scans, from 4.8 to 3.9 (mean retention index, -17%; 95% confidence interval, -10% to -23%, P < 0.001). The mean malignant-to-benign ratio increased significantly, from 1.4 on the initial scan to 1.8 on the delayed scan (P = 0.003). The areas under the receiver operating characteristic curves for distinguishing dominant malignant regions from probable benign regions based on initial SUVmax, delayed SUVmax, and retention index were 0.81, 0.92, and 0.93, respectively. CONCLUSION: On dual-phase PET of the prostate, areas of malignancy consistently demonstrated stable or increasing 18F-fluorocholine uptake, whereas most areas containing benign tissue demonstrated decreasing uptake. Delayed or dual-phase imaging after injection of 18F-fluorocholine may improve the performance of 18F-fluorocholine PET for localizing malignant areas of the prostate.

Prostate cancer localization with 18fluorine fluorocholine positron emission tomography.

PURPOSE: We evaluated positron emission tomography (PET) with fluorine fluorocholine (F FCH) for the pretreatment localization of prostate cancer. MATERIALS AND METHODS: A total of 17 patients with prostate cancer who had not yet received treatment for the disease underwent whole body PET following intravenous administration of 3.3 to 4 MBq/kg F FCH. PET findings were compared with the results of prostate sextant biopsy and other imaging studies, and the clinical course. Tracer uptake in prostate sextants was measured as a maximum standardized uptake value (SUVmax) and evaluated as a predictor of the prostate sextant biopsy result by ROC analysis. RESULTS: Prostate sextants positive for malignancy on biopsy demonstrated significantly higher SUVmax than biopsy negative sextants (mean 5.5 vs 3.3, p <0.001). In all 6 cases in which biopsy identified malignancy on only 1 side of the prostate it was possible to identify correctly the affected side based on higher SUVmax. Area under the ROC curve for SUVmax as a discriminator of biopsy positive sextants was 0.86. In 2 patients PET demonstrated areas of abnormal uptake in the retroperitoneum. Computerized tomography confirmed the presence of retroperitoneal lymphadenopathy in these areas. In the 2 patients these lesions regressed following hormonal treatment for prostate cancer. CONCLUSIONS: Malignant tumors in the prostate gland can be localized based on a standardized regional measurement of F FCH uptake. PET with F FCH is potentially useful for staging and localizing prostate cancer.

Combined use of F-18 fluorocholine positron emission tomography and magnetic resonance spectroscopy for brain tumor evaluation.

BACKGROUND: Choline metabolism is often abnormal in malignant brain tumors. METHODS: Brain positron emission tomography (PET) imaging with F-18 fluorocholine (FCH) was performed on 2 patients with intracranial lesions suspected to be high-grade malignant gliomas on the basis of magnetic resonance (MR) imaging and multivoxel 1H-MR spectroscopic imaging (MRSI) findings. Standardized uptake value (SUV) measurements on PET were compared with measurements of choline/creatine metabolite ratio on MRSI in corresponding regions. Brain biopsy revealed glioblastoma multiforme (GBM) in one case and demyelinating disease in the other. RESULTS: In the case of GBM, the tumor demonstrated increased FCH uptake on PET. The mean and maximum SUV in areas of the tumor correlated with regional choline/creatine ratio measurements (r = 0.76, P < .001; r = 0.83, P < .001, respectively). In the case of tumefactive demyelinating lesions, the lesion demonstrated low FCH uptake, which did not correlate with choline/creatine ratio measurements. CONCLUSIONS: Assessments of choline metabolism may aid in evaluating intracranial mass lesions.

Reduction of myocardial 2-deoxy-2-[18F]fluoro-D-glucose uptake artifacts in positron emission tomography using dietary carbohydrate restriction.

PURPOSE: The use of carbohydrate restriction prior to 2-deoxy-2-[18F] positron emission tomography (FDG-PET) to reduce image artifacts caused by myocardial FDG uptake was investigated. PROCEDURES: Ninety-six whole-body FDG-PET scans were studied. Dietary intake of the meal prior to scanning was recorded. Coronal and transverse images were assessed visually and scored based on myocardial FDG uptake and the presence of associated image artifacts. RESULTS: Of 49 patients who consumed carbohydrates prior to PET, 14 (28.6%) had a clinically significant image artifact versus only five (10.6%) of 47 patients who did not consume carbohydrates (P = 0.0275). A 3.36 times increased risk (confidence interval 1.00-12.97) for clinically significant image artifacts was calculated for patients who consume carbohydrates in their last meal prior to scanning. CONCLUSIONS: With the rising use of FDG-PET in the evaluation of intra-thoracic malignancies, dietary carbohydrate restriction prior to scanning may play a role in increasing lesion detectability and reducing false negative scans.