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 most patients develop progression. To our knowledge, this is the first report evaluating Zr-trastuzumab in HER2-positive EGA; here, we evaluate the safety, pharmacokinetics, biodistribution, and dosimetryZr-trastuzumab. Trastuzumab was conjugated with deferoxamine and radiolabeled withZr. 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. No clinically significant toxicities were observed. At the end of infusion, the estimatedZr-trastuzumab in plasma volume was a median 102% (range, 78%-113%) of the injected dose. The median biologic half-life T was 111 h (range, 78-193 h). The median biologic whole-body retention half-life was 370 h (range, 257-578 h). PET images showed optimal tumor visualization at 5-8 d after injection. The maximum tumor SUV ranged from no to minimal uptake in 3 patients to a median of 6.8 (range, 2.9-22.7) for 20 lesions in 7 patients. Dosimetry estimates from OLINDA showed that the organs receiving the highest absorbed doses were the liver and heart wall, with median values of 1.37 and 1.12 mGy/MBq, respectively. 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 d after injection.

DSRCT typically presents as a large abdominopelvic mass with widespread peritoneal involvement predominantly in young males. Familiarity with its radiological features can help guide diagnosis and treatment. Functional imaging with PET/CT offers advantage over anatomical imaging for accurate disease staging.

Our study illustrates a method to evaluate the standard of practice for thyroid nodule assessment among radiologists within an ultrasound group. Application of a 5-point malignancy rating scale to select nodules for biopsy is feasible and shows good diagnostic accuracy.

IntroductionThe objective of the study was to determine the relative importance (RI) of treatment attributes psoriasis patients and physicians consider when choosing between biologic therapies based on psoriasis severity.MethodsA discrete choice experiment (DCE) weighting preference for eight sets of hypothetical treatments for moderate or severe psoriasis was conducted. DCE hypothetical treatments were defined and varied on combinations of efficacy, safety, and dosing attributes [frequency/setting/route of administration (ROA)].ResultsWhen assuming moderate psoriasis in the patient DCE, ROA (RI 29%) and efficacy (RI 27%) drive treatment choices. When assuming severe disease in the DCE, patients preferred treatments with higher efficacy (RI 36%); ROA was relatively less important (RI 15%). From the physician perspective, ROA (RI 32%) and efficacy (RI 26%) were most important for moderate psoriasis patients. In the physician model for severe psoriasis, efficacy (RI 42%) was the predominant driver followed by ROA (RI 22%). Regardless of severity, probability of loss of response within 1 year was the least important factor.ConclusionsThe severity of disease is a critical element in psoriasis treatment selection. There are high levels of alignment between physician- and patient-derived preferences in biologic treatment choice selection for psoriasis.FundingJanssen Pharmaceuticals.

Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively newly identified target in prostate cancer. We evaluated the ability of PET/CT with 89 Zr-DFO-MSTP2109A, an antibody that recognizes STEAP1, to detect lesions in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Nineteen mCRPC patients were prospectively imaged using approximately 185 MBq/10 mg of 89 Zr-DFO-MSTP2109A. 89 Zr-DFO-MSTP2109A PET/CT images obtained 4-7 d after injection were compared with bone and CT scans. Uptake in lesions was measured. Fifteen patients were treated with an antibody-drug conjugate (ADC) based on MSTP2109A; ADC treatment-related data were correlated with tumor uptake by PET imaging. Bone or soft-tissue biopsy samples were evaluated. Results: No significant toxicity occurred. Excellent uptake was observed in bone and soft-tissue disease. Median SUV max was 20.6 in bone and 16.8 in soft tissue. Sixteen of 17 lesions biopsied were positive on 89 Zr-DFO-MSTP2109A, and all sites were histologically positive (1 on repeat biopsy). Bayesian analysis resulted in a best estimate of 86% of histologically positive lesions being true-positive on imaging (95% confidence interval, 75%-100%). There was no correlation between SUV max tumor uptake and STEAP1 immunohistochemistry, survival after ADC treatment, number of ADC treatment cycles, or change in prostate-specific antigen level. Conclusion: 89 Zr-DFO-MSTP2109A is well tolerated and shows localization in mCRPC sites in bone and soft tissue. Given the high SUV in tumor and localization of a large number of lesions, this reagent warrants further exploration as a companion diagnostic in patients undergoing STEAP1-directed therapy.

Our data on a small number of patients are in agreement with prior individual FDG or OCT reports and suggest that, overall, FDG PET/CT detects more MCC lesions and upgrades MCC stage compared with the OCT scan. Importantly, there were no lesions identified by OCT that were missed by PET. Thus, given the added resolution and sensitivity of PET, the use of OCT in MCC in the modern era is of limited value and it remains to be seen whether newer 68Ga-labeled somatostatin analogs will perform better than OCT.

The authors describe 3 cases of sclerosing angiomatoid nodular transformation (SANT) of the spleen diagnosed at Memorial Sloan-Kettering Cancer Center within a 1-year period (July 2008 to June 2009). All patients were female, older than 50, with lesions ranging in size from 2 to 4 cm. All were alive and well after splenectomy. All the cases showed characteristic histological and immunophenotypical findings as previously described in the literature, including scattered IgG4positive plasma cells in the fibrosclerotic stroma. Of the 3 patients, 2 had a history of carcinoma, and metastasis was of concern, but a PET scan in one of these patients showed minimal to absent FDG activity suggesting that this process was of a benign indolent nature. However, in 1 patient, a PET scan revealed positive FDG activity, heightening clinical concern for malignancy.

A six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a newly identified target in prostate cancer. The use of radio-labeled STEAP1-targeting antibodies with positron emission tomography (PET) may allow for detection of sites of metastatic prostate cancer and may refine patient selection for antigen-directed therapies. This was a prospective study in seven patients with metastatic castration-resistant prostate cancer who had at least one archival biopsy that was STEAP1-positive by immunohistochemistry. Patients received intravenous injections of ∼185 MBq and 10 mg of [89Zr]­Zr-DFO-MSTP2109A, a humanized IgG1 monoclonal antibody directed against STEAP1. PET/CT images, blood samples, and whole-body counts were monitored longitudinally in six patients. Here, we report on safety, biodistribution, pharmacokinetics, dose estimates to normal tissues, and initial tumor targeting for this group of patients. There was no significant acute or subacute toxicity. Favorable biodistribution and enhanced lesion uptake (in both bone and soft tissue) were observed on imaging using a mass of 10 mg of DFO-MSTP2109A. The best lesion discrimination was seen at the latest imaging time, a median of 6 days postadministration. Pharmacokinetics showed a median serum T 1/2 β of 198 h, volume of central compartment of 3.54 L (similar to plasma volume), and clearance of 19.7 mL/h. The median biologic T 1/2 for whole-body retention was 469 h. The highest mean absorbed doses to normal organs (mGy/MBq) were 1.18, 1.11, 0.78, 0.73, and 0.71 for liver, heart wall, lung, kidney, and spleen, respectively. Excellent targeting of metastatic prostate sites in both bone and soft tissue was observed, with an optimal imaging time of 6 days postadministration. The liver and heart were the normal organs that experienced the highest absorbed doses. The pharmacokinetics were similar to other antibodies without major cross-reactivity with normal tissues. A more detailed analysis of lesion targeting in a larger patient population with correlation to immunohistology and standard imaging modalities has been reported.