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Head-to-Head Comparison of 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT: A Prospective Study of 59 Patients with Neuroendocrine Tumors.
Johnbeck, CB, Knigge, U, Loft, A, Berthelsen, AK, Mortensen, J, Oturai, P, Langer, SW, Elema, DR, Kjaer, A
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017;(3):451-457
Abstract
Somatostatin receptor imaging is a valuable tool in the diagnosis, follow-up, and treatment planning of neuroendocrine tumor (NET). PET-based tracers using 68Ga as the radioisotope have in most centers replaced SPECT-based tracers as the gold standard. 64Cu-DOTATATE is a new PET tracer that has been shown to be far superior to the SPECT tracer 111In-diethylenetriaminepentaacetic acid-octreotide. Because of the advantages of 64Cu over 68Ga, we hypothesized that the tracer has a higher sensitivity than 68Ga-based tracers. To test this hypothesis, we compared on a head-to-head basis the diagnostic performance of 64Cu-DOTATATE with that of 68Ga-DOTATOC in NET patients. Methods: Fifty-nine NET patients were scanned with both 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT and compared on a head-to-head basis. Discordant lesions were verified during at least 30 mo of follow-up. Results: A total of 701 lesions were concordantly detected on both 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT scans, whereas an additional 68 lesions were found by only one of the scans. 64Cu-DOTATATE showed 42 lesions not found on 68Ga-DOTATOC, of which 33 were found to be true-positive on follow-up. 68Ga-DOTATOC showed 26 lesions not found on 64Cu-DOTATATE, of which 7 were found to be true-positive on follow-up. False-positives were mainly lymph node lesions. Accordingly, 83% of the additional true lesions found on only one of the scans were found by 64Cu-DOTATATE. On a patient-basis, additional true lesions were found by 64Cu-DOTATATE and 68Ga-DOTATOC in 13 and 3 patients, respectively. All patients with additional lesions also had concordant lesions found by both scans. Conclusion:64Cu-DOTATATE has advantages over 68Ga-DOTATOC in the detection of lesions in NET patients. Although patient-based sensitivity was the same for 64Cu-DOTATATE and 68Ga-DOTATOC in this cohort, significantly more lesions were detected by 64Cu-DOTATATE. Furthermore, the shelf life of more than 24 h and the scanning window of at least 3 h make 64Cu-DOTATATE favorable and easy to use in the clinical setting.
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Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.
Sachpekidis, C, Hillengass, J, Goldschmidt, H, Wagner, B, Haberkorn, U, Kopka, K, Dimitrakopoulou-Strauss, A
European journal of nuclear medicine and molecular imaging. 2017;(1):50-62
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Abstract
AIM: The aim of this study was to assess the combined use of the radiotracers 18F-FDG and 18F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). PATIENTS AND METHODS Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with 18F-FDG and 18F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). RESULTS An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, 18F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, 18F-FDG PET/CT-based treatment response revealed CR in 14 patients (18F-FDG PET/CT CR), PR in 11 patients (18F-FDG PET/CT PR) and progressive disease in four patients (18F-FDG PET/CT PD). In terms of 18F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, 18F-NaF PET/CT depicted 56 of the 129 18F-FDG positive lesions (43 %). Follow-up 18F-NaF PET/CT showed persistence of 81.5 % of the baseline 18F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to 18F-FDG negative. Treatment response according to 18F-NaF PET/CT revealed CR in one patient (18F-NaF PET/CT CR), PR in five patients (18F-NaF PET/CT PR), SD in 12 patients (18F-NaF PET/CT SD), and PD in seven patients (18F-NaF PET/CT PD). Dynamic 18F-FDG and 18F-NaF PET/CT studies showed that SUVaverage, SUVmax, as well as the kinetic parameters K1, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p < 0.001). CONCLUSION F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of 18F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, 18F-NaF PET/CT does not seem to add significantly to 18F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.
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Prospective Clinical Trial of 18F-Fluciclovine PET/CT for Determining the Response to Neoadjuvant Therapy in Invasive Ductal and Invasive Lobular Breast Cancers.
Ulaner, GA, Goldman, DA, Corben, A, Lyashchenko, SK, Gönen, M, Lewis, JS, Dickler, M
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017;(7):1037-1042
Abstract
18F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) is a leucine analog radiotracer that depicts amino acid transport into cells. 18F-fluciclovine PET/CT visualizes malignancy, including prostate cancer, invasive ductal breast cancer, and invasive lobular breast cancer. Whether changes in 18F-fluciclovine avidity reflect changes in tumor burden resulting from treatment has not been shown. In this prospective clinical trial (clinical trials.gov: NCT01864083), changes in 18F-fluciclovine avidity after neoadjuvant therapy were compared to breast cancer therapy response, as determined by residual tumor burden on pathology, were evaluated. Methods: Twenty-four women with a new diagnosis of locally advanced invasive ductal breast cancer (n = 18) or invasive lobular breast cancer (n = 6) underwent 18F-fluciclovine PET/CT before and after the completion of neoadjuvant systemic therapy. SUVmax, SUVmean, metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes on each examination and corrected for background 18F-fluciclovine avidity. The relationship between changes in 18F-fluciclovine avidity and the percentage of reduction of tumor on pathology was assessed with the Spearman rank correlation. Results: The median decrease in the corrected SUVmax of the primary breast lesions was 99% (range, 33%-100%). The median reduction of tumor on pathology was 92% (range, 10%-100%). Changes in 18F-fluciclovine avidity were strongly correlated with the percentage of reduction of tumor on pathology (Spearman ρ, 0.79; 95% CI, 0.56-0.90; P < 0.001). Conclusion: Changes in 18F-fluciclovine avidity strongly correlated with the tumor response on pathology in this pilot study.
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Comparison of 11C-Methionine and 18F-FDG PET/CT for Staging and Follow-up of Pediatric Lymphoma.
Kaste, SC, Snyder, SE, Metzger, ML, Sandlund, JT, Howard, SC, Krasin, M, Shulkin, BL
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017;(3):419-424
Abstract
Methionine transport across plasma membranes occurs via the large amino acid transporter, which is overexpressed in malignant cells, leading to tracer accumulation within tumors. We investigated the uptake of 11C-methionine (11C-MET) in children and young adults with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) and compared the biodistribution of 11C-MET PET/CT with that of 18F-FDG PET/CT. Methods: Conducted under an investigational new drug authorization, we prospectively enrolled patients with newly diagnosed HL (n = 19) and NHL (n = 2) onto the Institutional Review Board-approved investigation of 11C-MET PET/CT. After a minimum 4-h fast, patients received 740 MBq/1.7 m2 (maximum, 740 MBq [20 mCi/1.7 m2; maximum, 20 mCi]) of 11C-methionine intravenously. PET/CT was performed 5 min after injection from the vertex to thighs at 3 min per bed position. In a separate session, patients received 5.5 MBq/kg (maximum, 485 MBq [0.15 mCi/kg; maximum, 12 mCi]) of 18F-FDG with imaging initiated approximately 1 h after radiopharmaceutical administration. All studies were reviewed by consensus of 2 senior imaging specialists. The presence of metabolic activity on baseline studies was compared among 17 nodal groups. Results: Eighteen patients (11 male; median age, 15.2 y; age range, 9.5-22.6 y) comprised the study cohort. All had paired 11C-MET PET/CT and 18F-FDG PET/CT studies at diagnosis. At baseline, 3 nodal groups demonstrating discordant metabolic activity by both 18F-FDG PET/CT and 11C-MET PET/CT were Waldeyer's ring, paraaortic region, and the liver. All others were found to have concordant metabolic activity. Normal intense 11C-MET uptake in the pancreas and liver reduced sensitivity for disease detection in these regions. At follow-up, 14 of 15 study pairs had concordant results. Conclusion:11C-MET uptake is elevated in most regions involved with lymphoma at diagnosis and follow-up. Its utility in the abdomen is limited by uptake in normal structures.
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Initial Results of a Prospective Clinical Trial of 18F-Fluciclovine PET/CT in Newly Diagnosed Invasive Ductal and Invasive Lobular Breast Cancers.
Ulaner, GA, Goldman, DA, Gönen, M, Pham, H, Castillo, R, Lyashchenko, SK, Lewis, JS, Dang, C
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2016;(9):1350-6
Abstract
UNLABELLED (18)F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ((18)F-fluciclovine) is a leucine analog PET/CT radiotracer that depicts amino acid transport into cells. Amino acid transport proteins have been shown to be upregulated in breast malignancies by microarray and immunohistochemical analysis, so we hypothesized that (18)F-fluciclovine may provide a novel method of visualizing breast cancer and now report a prospective clinical trial of (18)F-fluciclovine PET/CT in newly diagnosed advanced local invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). METHODS Twenty-seven women with a new diagnosis of locally advanced IDC (n = 19) or ILC (n = 8) underwent PET/CT of the chest after intravenous administration of 370 MBq of (18)F-fluciclovine. The SUVmax, SUVmean, metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes. Sites of previously unsuspected malignancy were recorded and confirmed by pathology. Results of (18)F-fluciclovine PET/CT were compared with those of (18)F-FDG PET/CT, when available, using the concordance correlation coefficient. RESULTS All locally advanced breast cancers were (18)F-fluciclovine-avid. Of 21 patients with pathologically proven axillary nodal metastases, (18)F-fluciclovine-avid axillary nodes were seen in 20. (18)F-fluciclovine detected pathologically proven extraaxillary nodal metastases in 3 patients, including 2 previously unsuspected internal mammary nodes. Fourteen patients underwent (18)F-FDG PET/CT for comparison with (18)F-fluciclovine. Concordance for metabolic tumor volume between (18)F-fluciclovine and (18)F-FDG was strong (concordance correlation coefficient, 0.89; 95% confidence interval, 0.73-0.96), but concordance for SUVmax was weak (concordance correlation coefficient, 0.04; 95% confidence interval, -0.16-0.24). In patients with both modalities available (n = 14), primary ILCs (n = 4) demonstrated (18)F-fluciclovine avidity (median SUVmax, 6.1; range, 4.5-10.9) greater than (18)F-FDG avidity (median SUVmax, 3.7; range, 1.8-6.0). Primary IDCs (n = 10) had a lower (18)F-fluciclovine avidity (median SUVmax, 6.8; range, 3.6-9.9) than (18)F-FDG avidity (median SUVmax, 10; range, 3.3-43.5). CONCLUSION (18)F-fluciclovine PET/CT demonstrates potential for imaging of both IDC and ILC, including the detection of unsuspected extraaxillary nodal metastases. The low concordance for SUVmax between (18)F-fluciclovine and (18)F-FDG suggests that these tracers measure different biologic phenomena within the tumor. The apparently higher uptake of (18)F-fluciclovine in ILC requires confirmation in a larger cohort.