fluciclovine-f-18 and Bone-Neoplasms

Nonmetastatic castration-resistant prostate cancer (nmCRPC) presents a challenge to urologists as currently there are no Food and Drug Administration-approved therapies. However, there are new imaging modalities, including fluciclovine positron emission tomography-computed tomography and Ga-PSMA (prostate specific membrane antigent) positron emission tomography-computed tomography, which are improving accuracy of diagnosis. With improved imaging, we are better able to target therapy. Today there are 3 ongoing clinical trials studying second-generation antiandrogens in nmCRPC, which hold the promise of a new treatment paradigm. In this article, we will review the new imaging techniques and the rationale behind novel treatment modalities in nmCRPC.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Benzamides; Biomarkers, Tumor; Bone Neoplasms; Carboxylic Acids; Clinical Trials, Phase III as Topic; Cyclobutanes; Disease Management; Drug Resistance, Neoplasm; Humans; Kallikreins; Male; Multicenter Studies as Topic; Nitriles; Orchiectomy; Phenylthiohydantoin; Prostate-Specific Antigen; Prostatic Neoplasms; Pyrazoles; Randomized Controlled Trials as Topic

Prostate cancer is the most common cancer and the second leading cause of cancer death in men in the United States. Despite high disease prevalence, diagnosis and surveillance of the disease with conventional imaging are limited typically because of indolent biology. Functional imaging with advanced molecular techniques improves the ability to detect disease. Amino acids are building blocks of proteins, and intracellular transport of amino acids is upregulated in prostate cancer. This review provides a detailed overview of the use of F-18 fluciclovine PET in prostate cancer imaging.

Topics: Bone Neoplasms; Carboxylic Acids; Cyclobutanes; Drug Approval; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Multimodal Imaging; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postoperative Care; Practice Guidelines as Topic; Prostatectomy; Prostatic Neoplasms; Radiopharmaceuticals; Tomography, X-Ray Computed

Only few patients with PSA relapse after radical treatment will show clinically detectable disease. Although the natural history of recurrent prostate cancer is often one of the slowly progressing diseases, in some men it can be rapid and may need a salvage treatment. In general, time to PSA relapse, PSA velocity and PSA doubling time are useful in patient assesment. In patients with PCa disease relapse after primary therapy, salvage treatment for a local recurrence should only be offered to patients with little risk of already having metastases. In these patients a systemic imaging negative for metastases is mandatory, a positive biopsy is not always necessary before radiotherapy, but is mandatory before salvage prostatectomy. In patients with a high risk of distant metastases and suitable for systemic salvage therapy, a positive lesion must be obviously visualized with one of the currently available imaging techniques. Transrectal ultrasound has low accuracy in the detection of the recurrence. Multiparametric Magnetic Resonance Imaging may have a role in the early phase of PSA relapse. Conventional imaging, such as bone scan and CT, are not suggested in the initial phase of BCR. Today, it has been reported that PET/CT allows changing the therapeutic strategy (from palliative to curative treatment and vice-versa) in about 20% of cases. In recent years, the new radiotracer 18F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect PCa relapse. The aim of the present paper is to evaluate the management of patients with BCR after radical treatment of PCa from the urologist point of view.

Topics: Bone Neoplasms; Carbon Radioisotopes; Carboxylic Acids; Choline; Cyclobutanes; Fluorine Radioisotopes; Humans; Male; Multimodal Imaging; Neoplasm Metastasis; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Tomography, X-Ray Computed

One of the major challenges for all imaging modalities is accurate detection of prostate cancer (PCa) recurrence. Beyond the established Ga-PSMA, a novel promising PET tracer in PCa imaging is F-fluciclovine. For evaluating the advantages and disadvantages and the comparability, we conducted a prospective head-to-head comparison on F-fluciclovine and Ga-PSMA-11 in patients with biochemical recurrence of PCa.. 58 patients with biochemical recurrence of PCa after definitive primary therapy were included. Both scans were performed within a time window of mean 9.4 days. All scans were visually analyzed independently on a patient-, region- and lesion-based analysis. All the examinations were performed in the same medical department using identical scanners at any time.. The overall detection rate for PCa recurrence was 79.3% in F-fluciclovine and 82.8% in Ga-PSMA-11 (P = 0.64). Local recurrence was detected in 37.9% on F-fluciclovine and in 27.6% on Ga-PSMA-11 (P = 0.03). Local pelvic lymph node recurrence was detected on F-fluciclovine versus Ga-PSMA-11 in 46.6% versus 50%, in extrapelvic lymph node metastases in 41.4% versus 51.7% and in bone metastases in 25.9% versus 36.2%. Lesion-based analysis showed identical findings in local pelvic lymph nodes in 39.7%, in extrapelvic lymph nodes in 22.4%, and in bone metastases in 13.8%.. The advantage of F-fluciclovine is detecting curable localized disease in close anatomical relation to the urinary bladder, whereas Ga-PSMA-11 fails because of accumulation of activity in the urinary bladder. F-fluciclovine is almost equivalent to Ga-PSMA-11 in detecting distant metastases of PCa recurrence.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Carboxylic Acids; Cyclobutanes; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Humans; Lymphatic Metastasis; Male; Middle Aged; Oligopeptides; Positron Emission Tomography Computed Tomography; Prospective Studies; Prostatic Neoplasms; Recurrence

We performed a multicenter Phase IIb clinical trial of NMK36, a novel amino acid analog for positron emission tomography containing trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid, to evaluate its safety and diagnostic performance for primary prostate cancer.. Sixty-eight subjects with primary prostate cancer scheduled for radical prostatectomy or hormone therapy underwent whole-body positron emission tomography/computed tomography after injection of NMK36. The diagnostic performances of NMK36-positron emission tomography/computed tomography were evaluated for (i) regional lymph node metastasis: comparison with contrast-enhanced computed tomography under setting reference standard (histopathology or 6-month follow-up), (ii) bone metastasis: concordance rate with conventional imaging (combination of bone scintigraphy and contrast-enhanced computed tomography) and (iii) primary lesion: comparison with histopathological findings.. The accuracy of NMK36-positron emission tomography/computed tomography and contrast-enhanced computed tomography for regional lymph node metastasis were 85.5 and 87.3%, respectively. NMK36-positron emission tomography/computed tomography showed positive findings for regional lymph nodes with short-axis diameters of 5-9 mm at 23 regions in 13 patients of hormone therapy cohort, but they were not confirmed with reference standard in this study. The concordance rate of NMK36-positron emission tomography/computed tomography with conventional imaging for bone metastases was 83.3%, and seven patients had positive findings only by NMK36-positron emission tomography/computed tomography. The sensitivity and specificity of NMK36-positron emission tomography/computed tomography for primary lesion in six-segment analysis was 92.5 and 90.1%, respectively. Seven of non-serious adverse events were observed in six patients.. This study showed the comparable diagnostic performance of NMK36-positron emission tomography/computed tomography compared with conventional imaging. Some lesions of lymph node and bone were positive solely by NMK36-positron emission tomography/computed tomography, which needs to be confirmed with reference standard in future study to evaluate the usefulness of NMK36-positron emission tomography/computed tomography in staging prostate cancer.

Topics: Aged; Amino Acids; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Neoplasms; Carboxylic Acids; Contrast Media; Cyclobutanes; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiopharmaceuticals; Safety; Sensitivity and Specificity; Tomography, X-Ray Computed

To compare the accuracy of (18)F-FACBC and (11)C-choline PET/CT in patients radically treated for prostate cancer presenting with biochemical relapse.. This prospective study enrolled 100 consecutive patients radically treated for prostate cancer and presenting with rising PSA. Of these 100 patients, 89 were included in the analysis. All had biochemical relapse after radical prostatectomy (at least 3 months previously), had (11)C-choline and (18)F-FACBC PET/CT performed within 1 week and were off hormonal therapy at the time of the scans. The two tracers were compared directly in terms of overall positivity/negativity on both a per-patient basis and a per-site basis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for both the tracers; follow-up at 1 year (including correlative imaging, PSA trend and pathology when available) was considered as the standard of reference.. In 51 patients the results were negative and in 25 patients positive with both the tracers, in eight patients the results were positive with (18)F-FACBC but negative with (11)C-choline, and in five patients the results were positive with (11)C-choline but negative with (18)F-FACBC. Overall in 49 patients the results were false-negative (FN), in two true-negative, in 24 true-positive (TP) and in none false-positive (FP) with both tracers. In terms of discordances between the tracers: (1) in one patient, the result was FN with (11)C-choline but FP with (18)F-FACBC (lymph node), (2) in seven, FN with (11)C-choline but TP with (18)F-FACBC (lymph node in five, bone in one, local relapse in one), (3) in one, FP with (11)C-choline (lymph node) but TP with (18)F-FACBC (local relapse), (4) in two, FP with (11)C-choline (lymph nodes in one, local relapse in one) but FN with (18)F-FACBC, and (5) in three, TP with (11)C-choline (lymph nodes in two, bone in one) but FN with (18)F-FACBC. With (11)C-choline and (18)F-FACBC, sensitivities were 32 % and 37 %, specificities 40 % and 67 %, accuracies 32 % and 38 %, PPVs 90 % and 97 %, and NPVs 3 % and 4 %, respectively. Categorizing patients by PSA level (<1 ng/ml 28 patients, 1 - <2 ng/ml 28 patients, 2 - <3 ng/ml 11 patients, ≥3 ng/ml 22 patients), the number (percent) of patients with TP findings were generally higher with (18)F-FACBC than with (11)C-choline: six patients (21 %) and four patients (14 %), eight patients (29 %) and eight patients (29 %), five patients (45 %) and four patients (36 %), and 13 patients (59 %) and 11 patients (50 %), respectively.. (18)F-FACBC can be considered an alternative tracer superior to (11)C-choline in the setting of patients with biochemical relapse after radical prostatectomy.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Carbon Radioisotopes; Carboxylic Acids; Choline; Cyclobutanes; False Negative Reactions; Humans; Lymphatic Metastasis; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Recurrence

We present different findings on 18 F-fluciclovine (Axumin) PET/CT and 18 F-NaF PET/CT images in a patient with prostate cancer metastasis. 18 F-Fluciclovine PET/CT scan showed intense uptake in left adrenal gland metastasis, only faint to mild uptake in multiple sclerotic osseous metastasis where 18 F-NaF bone PET/CT demonstrated intense uptake at these sites. Both examinations are needed to accurately evaluate visceral and osseous metastasis from prostate cancer.

Topics: Bone Neoplasms; Carboxylic Acids; Cyclobutanes; Female; Genital Neoplasms, Female; Humans; Male; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms

F-Fluciclovine is the most recent prostate cancer (PCa)-directed PET radiotracer approved by the US Food and Drug Administration for detection of recurrent PCa. We report the treatments and outcomes of patients at our institution with PCa recurrences detected on F-fluciclovine PET/CT.. We identified men with recurrent PCa detected on F-fluciclovine PET/CT performed between 2017 and 2018 who were previously treated definitively and analyzed their patterns of care and cancer-specific outcomes.. We identified 28 men with recurrent PCa detected on F-fluciclovine PET/CT. Twenty-three were initially treated with surgery and 13 also received postoperative radiation therapy (RT). Five patients were initially treated with definitive radiation. After surgery, the median time to F-fluciclovine PET/CT was 67 months (median prostate-specific antigen [PSA] of 1.63 ng/mL). After RT, the median time to F-fluciclovine PET/CT was 95 months with median PSA of 13.31 ng/mL. Six men recurred locally, 9 recurred in the pelvic nodes, 9 had distant nodal recurrences, and 4 had osseous metastases. Of the patients initially treated with surgery, 4 received salvage radiation and 3 received androgen deprivation therapy (ADT). Of the patients initially treated with surgery and postoperative RT, 3 received salvage pelvic nodal dissection, 4 received salvage radiation, and 2 received ADT. Of the patients initially treated with radiation, 4 received salvage ADT. All had PSA decline after salvage therapy.. F-fluciclovine PET/CT can localize PCa recurrences, and subsequent salvage therapies appear effective with decreasing PSA. Longer follow-up will reveal if these diagnostic tests and subsequent therapies will improve PCa survival.

Topics: Aged; Androgen Antagonists; Bone Neoplasms; Carboxylic Acids; Cyclobutanes; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Recurrence; Salvage Therapy

A 76-year-old man presented with recently diagnosed prostate adenocarcinoma, Gleason score of 4 + 4, and a Super bone scan with concurrent PSA of 1.7 ng/mL. Approximately 3.5 months later, an F-fluciclovine PET/CT was performed despite of a decreased PSA of 0.3 ng/mL. A Superscan fluciclovine PET/CT was identified, and bone metastasis were later confirmed at biopsy.

Topics: Aged; Biopsy; Bone Neoplasms; Carboxylic Acids; Cyclobutanes; Humans; Male; Neoplasm Grading; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms

To compare the diagnostic performance of Fluciclovine PET/CT and 99mTc-MDP bone scan in detecting bone metastases in patients with metastatic prostate cancer.. Patients with metastatic prostate cancer who had both Fluciclovine PET/CT and bone scan within 3-month interval between October 2017 and October 2018 in our center were retrospectively reviewed. Exclusion criteria included separate concurrent cancer, or prostate-specific antigen were more than two-fold difference with an absolute difference >1 ng/ml between the two image studies. All abnormal bone lesions on either scan were compared. The findings were verified by available pathology and 4-month clinical follow-up.. A total of 106 patients with 106 dual scans were included in this study. 80/106 (75%) had concordant findings, whereas 26/106 (25%) had discordant findings. Of the discordant findings, 13/26 (50%) had false-positive findings on bone scan but negative on Fluciclovine PET/CT, 3/26 (11.5%) had positive lesions on Fluciclovine PET/CT but negative on bone scan, 8/26 (30.8%) had more positive lesions on Fluciclovine PET/CT than bone scan, and 2/26 (7.7%) with false-positive lesions on Fluciclovine PET/CT but negative on bone scan. The sensitivity, specificity, positive predictive value and negative predictive value for bone scan were 79%, 86%, 45% and 96%, respectively; and 100%, 98%, 89% and 100% in Fluciclovine PET/CT, respectively.. Our results demonstrated that Fluciclovine PET/CT detected more bone metastases than bone scan. Importantly, there were no lesions identified by bone scan that was missed by Fluciclovine PET/CT. With the extra capacity of detecting soft tissue metastasis in PET/CT, Fluciclovine PET/CT may render bone scan unnecessary to investigate metastatic prostate cancer.

Topics: Aged; Aged, 80 and over; Biopsy; Bone and Bones; Bone Neoplasms; Carboxylic Acids; Cyclobutanes; False Negative Reactions; False Positive Reactions; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Retrospective Studies; Technetium Tc 99m Medronate

F-fluciclovine is a synthetic amino acid radiotracer that has recently been approved in Europe and the United States for PET imaging in men with biochemical recurrence (BCR) of prostate cancer after prior definitive treatment. Accurate identification of the sites of disease in patients presenting with BCR of prostate cancer is important in determining the appropriate treatment. Bone is the most frequent site of metastatic disease in patients with prostate cancer.. We conducted a comprehensive review of the available preclinical and clinical data on the diagnostic performance of F-fluciclovine PET/CT in an attempt to draw practical and general conclusions on the utility and limitations of F-fluciclovine PET/CT in localization of osseous metastatic disease in prostate cancer.. The cumulative preclinical data and results of some retrospective and 2 prospective clinical studies suggest that F-fluciclovine can detect early bone marrow involvement in patients with BCR of prostate cancer and negative prior bone-specific imaging findings.. F-fluciclovine PET/CT seems to offer useful information for early detection of bone metastases in men with BCR of prostate cancer. Additional investigations will be needed to compare the diagnostic performance of F-fluciclovine PET/CT to other standard and novel imaging methods in initial staging, BCR, and castrate-resistant phases of disease.

Topics: Aged; Bone Neoplasms; Carboxylic Acids; Cyclobutanes; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals

Diagnosing bone metastases with traditional anatomic modalities, such as MRI and CT, is limited by sensitivity, and conventional bone radiotracers are only indirect markers of cancer activity. Fortunately, molecular imaging is uniquely capable of providing radiotracers such as fluciclovine and radiolabeled choline, that actually target tumors in the bone. The merits of research in imaging osseous metastases in animal models using these radiotracers and the implications for future clinical translation are discussed.

Topics: Animals; Bone Neoplasms; Carboxylic Acids; Cyclobutanes; Disease Models, Animal; Molecular Imaging; Neoplasm Metastasis; Positron-Emission Tomography

Topics: Animals; Bone Neoplasms; Breast Neoplasms; Carboxylic Acids; Cyclobutanes; Disease Models, Animal; Male; Neoplasm Metastasis; Positron-Emission Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Rats

To compare the diagnostic performance of the synthetic amino acid analogue PET radiotracer anti-3-[(18)F]FACBC (fluciclovine) with that of CT in the detection of recurrent prostate carcinoma.. This was a retrospective analysis of 53 bone scan-negative patients with suspected recurrent prostate carcinoma who underwent fluciclovine PET/CT and routine clinical CT within 90 days of each other. The correlation between imaging findings and histology and clinical follow-up was evaluated. Positivity rates and diagnostic performance were calculated for fluciclovine PET/CT and CT.. Of 53 fluciclovine PET/CT and 53 CT examinations, 41 (77.4 %) and 10 (18.9 %), respectively, had positive findings for recurrent disease. Positivity rates were higher with fluciclovine PET/CT than with CT at all prostate-specific antigen (PSA) levels, PSA doubling times and original Gleason scores. In the prostate/bed, fluciclovine PET/CT was true-positive in 31 and CT was true-positive in 4 of 51 patients who met the reference standard. In extraprostatic regions, fluciclovine PET/CT was true-positive in 12 and CT was true-positive in 3 of 41 patients who met the reference standard. Of the 43 index lesions used to prove positivity, 42 (97.7 %) had histological proof. In 51 patients with sufficient follow-up to calculate diagnostic performance in the prostate/bed, fluciclovine PET/CT demonstrated a sensitivity of 88.6 %, a specificity of 56.3 %, an accuracy of 78.4 %, a positive predictive value (PPV) of 81.6 %, and a negative predictive value (NPV) of 69.2 %; the respective values for CT were 11.4 %, 87.5 %, 35.3 %, 66.7 % and 31.1 %. In 41 patients with sufficient follow-up to calculate diagnostic performance in extraprostatic regions, fluciclovine PET/CT demonstrated a sensitivity of 46.2 %, a specificity of 100 %, an accuracy of 65.9 %, a PPV of 100 %, and an NPV of 51.7 %; the respective values for CT were 11.5 %, 100 %, 43.9 %, 100 % and 39.5 %.. The diagnostic performance of fluciclovine PET/CT in recurrent prostate cancer is superior to that of CT and fluciclovine PET/CT provides better delineation of prostatic from extraprostatic recurrence.

Topics: Aged; Bone Neoplasms; Carboxylic Acids; Cyclobutanes; Humans; Image Enhancement; Male; Middle Aged; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Tomography, X-Ray Computed