Oluwaseun Odewole

Anti-3-[18F]FACBC Positron Emission Tomography-Computerized Tomography and 111In-Capromab Pendetide Single Photon Emission Computerized Tomography-Computerized Tomography for Recurrent Prostate Carcinoma: Results of a Prospective Clinical Trial

PURPOSE We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[(18)F]FACBC compared to ProstaScint® ((111)In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. MATERIALS AND METHODS A total of 93 patients met study inclusion criteria who underwent anti-3-[(18)F]FACBC positron emission tomography-computerized tomography plus (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. RESULTS In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[(18)F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to (111)In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[(18)F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to (111)In-capromab pendetide with 10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[(18)F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. CONCLUSIONS Better diagnostic performance was noted for anti-3-[(18)F]FACBC positron emission tomography-computerized tomography than for (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for prostate carcinoma recurrence. The former method detected significantly more prostatic and extraprostatic disease.

Anti-1-Amino-3-18F-Fluorocyclobutane-1-Carboxylic Acid: Physiologic Uptake Patterns, Incidental Findings, and Variants That May Simulate Disease

Anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) is a synthetic amino acid analog PET radiotracer undergoing clinical trials for the evaluation of prostate and other cancers. We aimed to describe common physiologic uptake patterns, incidental findings, and variants in patients who had undergone 18F-FACBC PET. Methods: Sixteen clinical trials involving 611 18F-FACBC studies from 6 centers, which included dosimetry studies on 12 healthy volunteers, were reviewed. Qualitative observations of common physiologic patterns, incidental uptake, and variants that could simulate disease were recorded and compared with similar observations in studies of the healthy volunteers. Quantitative analysis of select data and review of prior published reports and observations were also made. Results: The liver and pancreas demonstrated the most intense uptake. Moderate salivary and pituitary uptake and variable mild to moderate bowel activity were commonly visualized. Moderate bone marrow and mild muscle activity were present on early images, with marrow activity decreasing and muscle activity increasing with time. Brain and lungs demonstrated activity less than blood pool. Though 18F-FACBC exhibited little renal excretion or bladder uptake during the clinically useful early imaging time window, mild to moderate activity might accumulate in the bladder and interfere with evaluation of adjacent prostate bed and seminal vesicles in 5%–10% of patients. Uptake might also occur from benign processes such as infection, inflammation, prostatic hyperplasia, and metabolically active benign bone lesions such as osteoid osteoma. Conclusion: Common physiologic uptake patterns were similar to those noted in healthy volunteers. The activity in organs followed the presence of amino acid transport and metabolism described with other amino acid–based PET radiotracers. As with other PET radiotracers such as 18F-FDG, focal nonphysiologic uptake may represent incidental malignancy. Uptake due to benign etiologies distinct from physiologic background also occurred and could lead to misinterpretations if the reader is unaware of them.

Multisite Experience of the Safety, Detection Rate and Diagnostic Performance of Fluciclovine (18F) Positron Emission Tomography/Computerized Tomography Imaging in the Staging of Biochemically Recurrent Prostate Cancer

Purpose: Sensitive detection of cancer foci in men experiencing biochemical recurrence following initial treatment of prostate cancer is of great clinical significance with a possible impact on subsequent treatment choice. We describe a multisite experience of the efficacy and safety of the positron emission tomography/computerized tomography agent fluciclovine (18F) after biochemical recurrence. Materials and Methods: A total of 596 patients underwent fluciclovine (18F) positron emission tomography/computerized tomography at 4 clinical sites. Detection rate determinations were stratified by the baseline prostate specific antigen value. Diagnostic performance was assessed against a histological reference standard in 143 scans. Results: The subject level fluciclovine (18F) positron emission tomography/computer tomography detection rate was 67.7% (403 of 595 scans). Positive findings were detected in the prostate/bed and pelvic lymph node regions in 38.7% (232 of 599) and 32.6% of scans (194 of 596), respectively. Metastatic involvement outside the pelvis was detected in 26.2% of scans (155 of 591). The subject level detection rate in patients in the lowest quartile for baseline prostate specific antigen (0.79 ng/ml or less) was 41.4% (53 of 128). Of these patients 13 had involvement in the prostate/bed only, 16 had pelvic lymph node involvement without distant disease and 24 had distant metastases. The positive predictive value of fluciclovine (18F) positron emission tomography/computerized tomography scanning for all sampled lesions was 62.2%, and it was 92.3% and 71.8% for extraprostatic and prostate/bed involvement, respectively. Fluciclovine (18F) was well tolerated and the safety profile was not altered following repeat administration. Conclusions: Fluciclovine (18F) is well tolerated and able to detect local and distant prostate cancer recurrence across a wide range of prostate specific antigen values.

Near-elimination of folate-deficiency anemia by mandatory folic acid fortification in older US adults: Reasons for Geographic and Racial Differences in Stroke study 2003–2007

BACKGROUND The United States implemented mandatory folic acid fortification of enriched cereal grains in 1998. Although several studies have documented the resulting decrease in anemia and folate deficiency, to our knowledge, no one has determined the prevalence of folate-deficiency anemia after fortification. OBJECTIVE We determined the prevalence of folate deficiency and folate-deficiency anemia within a sample of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. DESIGN The REGARDS cohort is a prospective cohort of 30,239 black and white participants living in the contiguous United States. We measured serum folate concentrations in a random sample of 1546 REGARDS participants aged ≥50 y with baseline hemoglobin and red blood cell mean corpuscular volume measurements. Folate deficiency was defined as a serum folate concentration <6.6 nmol/L (<3.0 ng/mL), and anemia was defined as a hemoglobin concentration <13 g/dL in men and <12 g/dL in nonpregnant women (WHO criteria). Folate-deficiency anemia was defined as the presence of both folate deficiency and anemia. RESULTS The mean hemoglobin concentration was 13.6 g/dL, and 15.9% of subjects had anemia. The median serum folate concentration was 34.2 nmol/L (15.1 ng/mL), and only 2 of 1546 participants 0.1%) were folate deficient. Both subjects were African American women with markedly elevated C-reactive protein concentrations, macrocytosis, and normal serum cobalamin concentrations; only one subject was anemic. Overall, the prevalence of folate-deficiency anemia was <0.1% (1 of 1546 subjects). CONCLUSION Our data suggest that, after mandatory folic acid fortification, the prevalence of folate-deficiency anemia is nearly nonexistent in a community-dwelling population in the United States.

Anti-3-18F-FACBC (18F-Fluciclovine) PET/CT of Breast Cancer: An Exploratory Study

The purpose of this study was to explore the uptake of the synthetic amino acid analog PET radiotracer anti-3-18F-FACBC (18F-fluciclovine) in breast lesions with correlation to histologic and immunohistochemical characteristics. Methods: Twelve women with breast lesions underwent 45-min dynamic PET/CT of the thorax after intravenous administration of 366.3 ± 14.8 (337.44–394.05) MBq of 18F-fluciclovine. Uptake in the primary lesions at 4 representative time points (5, 17, 29, and 41 min) after injection were correlated with histologic, imaging, and clinical findings. The significance of differences in SUVmax and tumor-to-background ratios between malignant and benign tissue were calculated. Correlations of activity to histologic and immunohistochemical cancer subtypes were made including Ki-67 intensity and Nottingham grade (NG). Results: There were 17 breast lesions (4 benign, 13 malignant) including 7 of 13 invasive ductal, 5 of 13 invasive lobular, and 1 of 13 metaplastic carcinomas. There was a significant difference in mean SUVmax ± SD of malignant (6.2 ± 3.2, 6.0 ± 3.2, 5.7 ± 2.8, and 5.6 ± 3.0) versus benign (1.3 ± 0.6, 1.2 ± 0.5, 1.2 ± 0.6, and 1.1 ± 0.5) lesions at 5, 17, 29, and 41 min, respectively (all P ≤ 0.0001). Tumor-to-background (aorta, normal breast, and marrow) ratios were also significantly higher in malignant than benign breast lesions (all P ≤ 0.02). The highest 18F-fluciclovine activity seems to be present in triple-negative and NG3 subtypes. Across time points, quantitative Ki-67 had weak positive correlation with SUVmax (R1 = 0.48 [P = 0.03], R2 = 0.44 [P = 0.03], R3 = 0.46 [P = 0.03], R4 = 0.43 [0.06]). In 7 patients, 18F-fluciclovine PET visualized locoregional and distant spread including that of lobular cancer, though identification of hepatic metastases was limited by physiologic background activity. Conclusion: The uptake characteristics of 18F-fluciclovine are reflective of the histologic and immunohistochemical characteristics in suspected breast lesions with greater activity in malignant versus benign etiology. The data from this exploratory study may be useful to design future studies using 18F-fluciclovine PET for breast tumor imaging as well as for detection of locoregional and distant spread.

Change in Salvage Radiotherapy Management Based on Guidance With FACBC (Fluciclovine) PET/CT in Postprostatectomy Recurrent Prostate Cancer.

Purpose We explored the influence of FACBC (fluciclovine) PET/CT on the decision to offer radiotherapy and radiotherapy treatment field recommendations in postprostatectomy patients with recurrent prostate cancer. Patients and Methods After obtaining institutional review board approval and informed consent, 87 patients with detectable prostate-specific antigen (PSA) levels were recruited into a prospective clinical trial. After an initial provider-determined radiotherapy plan based on conventional imaging, 44 of 87 patients were randomized to additionally undergo fluciclovine PET/CT. Pre- and post-fluciclovine radiotherapy decisions were compared and changes were noted. Statistical significance of these decision changes was determined. Results Two of 44 patients in the experimental arm dropped out before fluciclovine scanning. Thirty-four (81.0%) of 42 had positive results on fluciclovine. Overall radiotherapy decision was changed in 17 (40.5%) of 42. Mean PSA, original Gleason score, and prostatectomy-PET interval did not differ significantly between patients with and without radiotherapy decision changes. Two (4.8%) of 42 had the decision for radiotherapy withdrawn due to positive extrapelvic findings. Radiotherapy field decision was changed in 15 (35.7%) of 42. Eleven (73.3%) of 15 had fields changed from prostate bed only to both prostate bed and pelvis, while 4 (26.7%) of 15 had fields changed from both prostate bed and pelvis to prostate bed only. Changes in overall radiotherapy decision and field were statistically significant (P < 0.0001). However, the change in the decision to offer radiotherapy or not was not statistically significant (P = 0.15). Conclusions Fluciclovine PET/CT significantly changed radiotherapy management decisions in postprostatectomy patients with recurrent prostate cancer. Further work in determining differences in PSA-free survival is ongoing.

Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin Users in REGARDS, 2003-2007

Metformin, an insulin-sensitizing drug, is a first line treatment for type 2 diabetes. Long-term use of metformin has been associated with subsequent reductions in vitamin B12 concentrations. The objective of our study was to determine whether metformin use is associated with lower serum vitamin B12 concentrations in older adults, and whether concurrent use of multivitamins modifies this association. We examined 2,510 participants aged 50 years and over, participating in the national population-based Reasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Multivariable linear and logistic regression models were used to assess associations between multivitamin use and serum vitamin B12 concentrations. We estimated adjusted odds ratios (aOR)s and confidence intervals (CI)s. Results were stratified by three metformin/diabetes sub-groups: 1) participants with diabetes who were metformin users; 2) participants with diabetes who were not metformin users; and 3) participants without diabetes. We found that diabetic metformin users had significantly lower geometric mean serum B12 concentrations (409 pmol/L) than the group with diabetes not taking metformin (485 pmol/L; P<0.01), and the group without diabetes (445 pmol/L; P = 0.02). The geometric mean serum B12 concentrations were greater for multivitamin users (509 pmol/L) compared to those who did not use multivitamins (376 pmol/L; p<0.01). Among the participants with diabetes who were on metformin therapy, multivitamin use was associated with geometric mean serum vitamin B12 concentrations that were 50% (or 161 pmol/L) higher, compared to those not using multivitamins. Among metformin users, multivitamin use was associated with lower prevalence of combined low and borderline vitamin B12 concentrations (aOR = 0.14; 95% CI = 0.04, 0.54) compared to those not using multivitamins. In conclusion, metformin use was associated with lower geometric mean serum vitamin B12 concentrations among diabetic older adults compared to their counterparts. Concurrent multivitamin use may potentially protect against low or borderline vitamin B12 concentrations in long-term metformin users. Additional research is needed to further examine this association as low or borderline vitamin B12 concentrations can be preventable, or treatable if detected at an early stage, in long-term metformin users.

Racial and Ethnic Disparities in Graft and Recipient Survival in Elderly Kidney Transplant Recipients

To investigate racial and ethnic differences in graft and recipient survival in elderly kidney transplant recipients.