OBJECTIVE. The objective of this study was to optimize CT protocols for whole-body PET/CT by reducing radiation dose while minimizing effects on image quality. MATERIALS AND METHODS. Before protocol optimization, a survey of 140 consecutive patients was conducted to establish the baseline dose from a whole-body PET/CT examination. Another sample of 100 patients was surveyed to evaluate the reduction of radiation dose after implementation of the new protocol. Effective dose from the CT component of the examination was estimated using dose-length product (DLP) values from reports generated by the scanner and anatomy-specific conversion factors. Twenty-six patients who underwent studies before and after the optimization were included in an analysis of image quality. All 26 patients had maintained the same weight between the examinations and were scanned in the same position using a similar technique except for the changes made for CT dose optimization. The studies were randomized and blinded for an experienced PET and CT reader who graded the imaging quality of anatomic structures. RESULTS. CT protocol optimization resulted in a 32% reduction of the mean CT radiation dose: The mean effective dose was reduced from 8.1 to 5.5 mSv. The blinded analysis of image quality showed no clinically significant degradation of the lower-dose studies. The only structures visualized statistically better on the higher-dose CT scans were the carotid arteries and the region of the posterior triangle. CONCLUSION. The results of this study showed that optimization of CT acquisition can effectively reduce radiation dose in a whole-body PET/CT examination without significantly sacrificing image quality.
Learning Objectives: On successful completion of this activity, participants should be able to (1) understand the requirements for first-inhuman radiopharmaceutical applications for the United States, European Union, and Canada; (2) realize the overall need for reduction of the human-use requirements due to lack of toxicity and the need to facilitate patient access; and (3) recognize that harmonization efforts between the U.S. Food and Drug Administration, Health Canada, and the European Medical Authority would streamline efforts in moving new radiopharmaceuticals forward for clinical care.
Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.
The effect of priming on occult tumor cell involvement of peripheral blood (PB) and PB progenitor cell (PBPC) collections is poorly characterized. Using sensitive immunocytochemistry (ICC) and tumor clonogenic assays (TCA) specific for epithelial-derived tumor cells, hematopoietic specimens were analyzed for PBPC and occult tumor cell involvement in 28 patients with chemotherapy-sensitive stage IIIB or IV breast cancer. Before PBPC priming, tumor was detected by ICC in PB of 1 of 23 (4%) patients and in bone marrow (BM) harvests of 4 of 27 (15%) patients. Fifteen days after cyclophosphamide and granulocyte- macrophage colony-stimulating factor (GM-CSF) priming, 2 of 28 (7%) patients had ICC-positive PBPC collections. The median amplification of CD34+ PBPC during this time was over 19-fold (range, < 1 to 199). One patient had pretreatment tumor involvement of both PB and BM. One patient grew tumor colonies in TCA; the PB and BM were ICC- and TCA- positive, but the PBPC collection was ICC-positive and TCA-negative. After cytoreduction with conventional-dose chemotherapy, patients with advanced breast cancer and histologically negative BM biopsy specimens have rare tumor cell involvement of PB and BM. Despite effective PBPC priming with cyclophosphamide and GM-CSF, clonogenic breast cancer cells were not found in the PBPC collection performed on day 15.
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