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Tumor Uptake of (64)Cu-DOTA-Trastuzumab in Patients with Metastatic Breast Cancer.
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Tumor Uptake of (64)Cu-DOTA-Trastuzumab in Patients with Metastatic Breast Cancer.

J Nucl Med. 2017 Jun 21;:

Authors: Mortimer JE, Bading JR, Park JM, Frankel PH, Carroll MI, Tran TT, Poku EK, Rockne RC, Raubitschek AA, Shively JE, Colcher DM

Abstract
Purpose: To characterize the relationship between tumor uptake of (64)Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Experimental Design: Women with biopsy-confirmed MBC and not given trastuzumab for [&ge] 2 months underwent complete staging, including (18)F-fluorodeoxyglucose PET/CT. Patients were classified as HER2-positive (HER2+) or negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented IHC of biopsied tumor tissue. Eighteen patients underwent (64)Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21-25 ("Day 1") and 47-49 ("Day 2") h after (64)Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as maximum single-voxel standardized uptake value (SUVmax). Average intra-patient SUVmax (pt) was compared between HER2+ and - patients. Results: Eleven women were HER2+ (8 IHC 3+, 3 IHC 2+/FISH amplified), while 7 were HER2- (3 IHC 2+/FISH non-amplified; 4 IHC 1+). Median pt (Day 1, Day 2) was (6.6, 6.8 g/ml) for HER 2+ and (3.7, 4.3 g/ml) for HER2- patients (P<0.005 either day). The distributions of pt overlapped between the two groups, and inter-patient variability was greater for HER2+ than HER2- disease (P<0.005 and 0.001, respectively, on Days1 and 2). Conclusion: By 1 day after injection, uptake of (64)Cu-DOTA-trastuzumab in MBC is strongly associated with patient HER2 status. The variability within and among patients, as well as the overlap between the HER2+ and HER2- groups, suggests a role for (64)Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab.

PMID: 28637802 [PubMed - as supplied by publisher]




Accuracy in the eye of the beholder: can we improve agreement in prostate cancer diagnostics with PSMA PET/CT?
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Accuracy in the eye of the beholder: can we improve agreement in prostate cancer diagnostics with PSMA PET/CT?

J Nucl Med. 2017 Jun 21;:

Authors: Hofman MS

PMID: 28637801 [PubMed - as supplied by publisher]




Pharmacokinetics, biodistribution, and radiation dosimetry for (89)Zr-trastuzumab in patients with esophagogastric cancer.
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Pharmacokinetics, biodistribution, and radiation dosimetry for (89)Zr-trastuzumab in patients with esophagogastric cancer.

J Nucl Med. 2017 Jun 21;:

Authors: O'Donoghue JA, Lewis JS, Pandit-Taskar N, Fleming SE, Schoder H, Larson SM, Beylergil V, Ruan S, Lyashchenko S, Zanzonico PB, Weber WA, Carrasquillo JA, Janjigian YY

Abstract
Trastuzumab with chemotherapy improves clinical outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive esophagogastric adenocarcinoma (EGA). Despite the therapeutic benefit, responses are rarely complete and the majority of patients develop progression. This is the first report evaluating (89)Zr-trastuzumab in HER2-positive EGA in which we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry. Methods: Trastuzumab was conjugated with deferoxamine and radiolabeled with (89)Zr. A mean activity of 184 MBq was administered to 10 patients with metastatic HER2-positive EGA. PET imaging, whole-body probe counts, and blood draws were performed to assess pharmacokinetics, biodistribution and dosimetry. Results: No clinically significant toxicities were observed. At the end of infusion, the estimated (89)Zr-trastuzumab in plasma volume was a median 102% (range 78-113%) of the injected dose. The median biologic T1/2 β was 111 h (range 78-193 h). Median biologic whole-body retention half-life was 370 h (range 257-578 h). PET images showed optimal tumor visualization at 5-8 days post-injection. The maximum tumor standard uptake value (SUV) ranged from no to minimal uptake in three patients to a median of 6.8 (range 2.9-22.7) for 20 lesions in seven patients. Dosimetry estimates from Organ Level Internal Dose Assessment (OLINDA) showed that the organs receiving the highest absorbed doses were liver and heart wall with median values of 1.37 and 1.12 mGy/MBq, respectively. Conclusion:(89)Zr-trastuzumab imaging tracer is safe and provides high-quality images in patients with HER2-positive EGA, with an optimal imaging time of 5-8 days post-injection.

PMID: 28637800 [PubMed - as supplied by publisher]




(68)Ga-PSMA PET/CT and volumetric morphology of PET-positive lymph nodes stratified by tumor differentiation of prostate cancer.
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(68)Ga-PSMA PET/CT and volumetric morphology of PET-positive lymph nodes stratified by tumor differentiation of prostate cancer.

J Nucl Med. 2017 Jun 21;:

Authors: Vinsensia M, Choyke PL, Hadaschik B, Holland-Letz T, Moltz J, Kopka K, Rauscher I, Mier W, Schwaiger M, Haberkorn U, Maurer T, Kratochwil C, Eiber M, Giesel F

Abstract
(68)Ga prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computer tomography (CT) is a new method to detect early nodal metastases in patients with biochemical relapse of prostate cancer (PCa). In this retrospective investigation the dimensions, volume, localization and maximum standardized uptake value (SUVmax) of nodes identified by (68)Ga-PSMA were correlated to their Gleason score (GS) at diagnosis. Methods: All PET/CT images were acquired 60±10 min after intravenous injection of (68)Ga-PSMA (mean dose 176 MBq). In 147 prostate cancer patients (mean age 68; range 44-87 y) with prostate specific antigen (PSA) relapse (mean PSA level 5 ng/mL; range 0.25-294 ng/mL), 362 (68)Ga-PSMA PET positive lymph nodes (LN) were identified. These patients were classified based on their histopathology at primary diagnosis into either low (GS≤6, well-differentiated), intermediate (GS=7, moderately-differentiated) or high GS cohorts (GS≥8, poor-differentiated PCa). Using semi-automated LN segmentation software (MeVis, Bremen, GER), node volume, short and long axis dimensions (SAD, LAD) were measured based on CT and compared to the maximum standardized uptake value (SUVmax). Nodes demonstrating uptake of (68)Ga-PSMA with a SUVmax≥2.0 were considered PSMA-positive and nodes with SAD≥8 mm were considered positive by morphologic criteria. Results: Mean SUVmax was 13.5 (95% CI 10.9-16.1), 12.4 (95% CI 9.9-14.9) and 17.8 (95% CI 15.4-20.3) within the low, intermediate and high GS, respectively. The morphologic assessment of the (68)Ga-PSMA positive LN demonstrated that the low GS cohort presented with smaller (68)Ga-PSMA positive LN (mean SAD 7.7 mm; n = 113) followed by intermediate (mean SAD 9.4 mm; n = 122) and high GS cohorts (mean SAD 9.5 mm; n = 127). Based on the CT morphology criteria, only 34% of low GS patients, 56% of intermediate GS patients and 53% of high GS patients were considered CT positive. Overall, (68)Ga-PSMA imaging led to a reclassification of stage in 90 patients (61%) from cN0 to cN1 over CT. Conclusion:(68)Ga-PSMA PET is a promising modality in biochemical recurrent prostate cancer patients for N-staging. Conventional imaging underestimates lymph-node involvement compared to PSMA-molecular staging score in each GS cohort. The sensitivity of (68)Ga-PSMA-PET/CT enables earlier detection of subcentimeter lymph node metastases in the biochemical recurrence setting.

PMID: 28637799 [PubMed - as supplied by publisher]