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(18)F-FDG PET/CT allows the direct measurement of metabolic tumor burden in a variety of different malignancies. The aim of this study was to assess whether metabolic tumor volume (MTV) determined by (18)F-FDG PET/CT could be used in the prediction of progression-free and overall survival in multiple myeloma patients.Forty-seven patients (18 women, 29 men; mean age ± SD, 63 ± 11 y) with stage IIIA disease who had undergone whole-body (18)F-FDG PET/CT were retrospectively evaluated. Images underwent a 3-dimensional region-of-interest analysis including all focal lesions with a maximum standardized uptake value2.5. The MTV of each lesion was calculated using an automated contouring program based on the standardized uptake value and developed with a threshold of 40% of the maximum standardized uptake value. The total MTV of each patient was defined as the sum of metabolic volume of all focal lesions. Patients were treated and then subjected to a mean follow-up period of 24 mo.In the 47 patients studied, MTV range was 1.3-316.3 mL, with a median of 23.7 mL. A direct, significant correlation was found between MTV and the percentage of diffuse infiltration of bone marrow by plasma cells (r = 0.46, P = 0.006), whereas hemoglobin levels were inversely correlated with MTV (r = -0.56, P = 0.0001). At follow-up, patients who developed progressive disease (n = 18) showed a significantly higher MTV (74.7 ± 19.3 vs. 29.8 ± 5.1 mL, P = 0.009) than patients without progressive disease (n = 29). Furthermore, patients who died of myeloma (n = 9) had a significantly higher MTV (123.2 ± 30.6 vs. 28.9 ± 4.2 mL, P = 0.0001) than survivors (n = 38). No differences in age, plasma cell infiltration, M protein, albumin, β2-microglobulin, performance status, International Staging System score, and presence or absence of a bone marrow transplant were found between groups. The MTV cutoff level was determined by receiver-operating-characteristic curve analysis, and the best discriminative value found for predicting progression-free and overall survival was 42.2 and 77.6 mL, respectively. By Kaplan-Meier analysis and log-rank testing, progression-free and overall survival at follow-up were significantly better in patients showing an MTV lower than the cutoff than in those having an MTV higher than the cutoff (χ(2) = 3.9, P = 0.04, and χ(2) = 56.3, P0.0001, respectively).The direct measurement of tumor burden obtained by calculating MTV on (18)F-FDG PET/CT images may be used in the prediction of progression-free and overall survival in myeloma patients.

Epidermal growth factor receptor (EGFR) mutational status, activation of downstream signaling, and effective apoptotic cascade are all factors that may affect the tumor response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Here we test whether 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET/CT can provide clues for the selection of patients with NSCLC as candidates for treatment with reversible and irreversible EGFR TKIs or combination treatment with Bcl-x(L) inhibitors. METHODS: HCC827, H1975, and H1650 NSCLC cells were subcutaneously injected into flanks of nude mice. Tumor-bearing animals were treated daily for 3 d by oral gavage with erlotinib at 50 and 150 mg/kg, CL-387,785 (an irreversible EGFR TKI) at 50 mg/kg, WZ4002 (a more potent irreversible EGFR TKI) at 25 and 50 mg/kg, ABT-263 (a Bcl-x(L) inhibitor) at 6.25 mg/kg, and a combination of erlotinib (50 mg/kg) and ABT-263 (6.25 mg/kg). Imaging studies were performed before and after 3 d of treatment by intravenous injection of 7.4 MBq of (18)F-FLT and small-animal PET/CT of animals at 1 h after injection. Quantitative analysis of reconstructed images of baseline and posttreatment scans was performed, and the percentage change in (18)F-FLT uptake in each animal was determined. Tumor sections were tested for Ki67 immunostaining and the percentage of apoptotic cells. RESULTS: Sensitive tumors (HCC827) showed mean decreases in (18)F-FLT uptake of 45% and 28% with high- and low-dose regimens of erlotinib, respectively. Resistant NSCLC cells bearing a T790M mutation (H1975) showed mean increases in (18)F-FLT uptake of 27% and 33% with high and low doses of erlotinib, respectively. Treatment with CL-387,785, low-dose WZ4002, and high-dose WZ4002 caused mean decreases in tracer uptake of 21%, 26%, and 36%, respectively. NSCLC cells that were resistant because of dysregulation of Bcl-2 family members (H1650) showed mean reductions in (18)F-FLT uptake of 49% and 23% with high and low doses of erlotinib, respectively, whereas the addition of ABT-263 did not affect tracer uptake but significantly increased the percentage of apoptotic cells in tumor sections. CONCLUSION: PET/CT with (18)F-FLT may contribute to the selection of patients who may benefit from treatment with reversible and irreversible EGFR TKIs and may provide clues about which patients with NSCLC may be candidates for combination treatment with erlotinib and Bcl-x(L) inhibitors.

Endovenous bisphosphonate therapy seems associated with osteonecrosis of the jaw. The aim of this study was to evaluate the additional diagnostic value of hybrid SPECT/CT in 99m Tc-methylene diphosphonate 3-phase bone scintigraphy of osteonecrosis of the jaw in bisphosphonate-treated patients. Methods: We studied 15 patients (12 women and 3 men) with extraoral tumors affected by lytic bone metastases and multiple myeloma. All patients were previously treated with intravenous bisphosphonates (zoledronic acid) for 1–3 y, were negative for dental disease at clinical examination, and had suspected osteonecrosis of the jaw. All 15 patients underwent panoramic x-ray orthopantomography, CT or MRI (or both), microbiologic examination, 3-phase bone scintigraphy, and SPECT/CT of the maxillary region. Results: Three-phase bonescintigraphy showed increased perfusion and an increased blood pool in 9 of 12 and 10 of 12 patients, respectively; at the metabolic phase, SPECT was positive in all patients and showed abnormal hyperactivity in the maxilla of 2 patients, in the mandible of 9 patients, and in both the mandible and the maxilla of 4 patients. Hybrid SPECT/CT was of particular value in 8 of 15 patients, allowing discrimination of the osteonecrotic core from nearby hyperactivity due to viable bone. Whole-body scintigraphy showed remote and multiple metastases in all patients. Orthopantomography showed nonspecific bone rarefaction in all patients but was not able to aid diagnosis of osteonecrosis of the jaw. CT and MRI showed anomalies in all symptomatic patients: CT was helpful in evaluating both cortical and trabecular bone aspects, and MRI was able to detect soft-tissue involvement but not cortical bone destruction. Conclusion: In appropriately selected oncology patients treated with bisphosphonates, an increased uptake of 99m Tc-methylene diphosphonate in maxillary bones may suggest probable osteonecrosis of the jaw. In such cases, SPECT/CT may be of value in increasing the diagnostic accuracy of bone scanning, providing a precise functional anatomic correlation for the definition of the extent of disease.

New imaging techniques have been introduced to assess the extent and severity of disease in multiple myeloma (MM) patients. The aim of our study was to compare newer imaging modalities-such as (18)F-FDG PET/CT, (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintigraphy, and MRI-to assess their relative contribution in the evaluation of MM patients at diagnosis.Thirty-three newly diagnosed patients with MM were prospectively studied. Diagnosis and staging were made according to standard criteria. All patients underwent whole-body (18)F-FDG PET/CT, whole-body (99m)Tc-MIBI, and MRI of the spine and pelvis within 10 d, and imaging findings were compared.(18)F-FDG PET/CT was positive in 32 patients (16 focal uptake, 3 diffuse uptake, 13 focal and diffuse uptake), (99m)Tc-MIBI was positive in 30 patients (6 focal, 11 diffuse, 13 focal and diffuse uptake), and MRI of the spine and pelvis was positive in 27 patients (6 focal, 13 diffuse, 8 focal and diffuse uptake). (18)F-FDG PET/CT showed a total of 196 focal lesions (178 in bones and 18 in soft tissues), of which 121 were in districts other than the spine and pelvis, whereas (99m)Tc-MIBI visualized 63 focal lesions (60 in bones and 3 in soft tissues), of which 53 were in districts other than the spine and pelvis. In the spinal and pelvic regions, (18)F-FDG PET/CT detected 75 focal lesions (35 in spine and 40 in pelvis), (99m)Tc-MIBI visualized 10 focal lesions (1 in spine and 9 in pelvis), and MRI detected 51 focal lesions (40 in spine and 11 in pelvis).In whole-body analysis, (18)F-FDG PET/CT performed better than (99m)Tc-MIBI in the detection of focal lesions, whereas (99m)Tc-MIBI was superior in the visualization of diffuse disease. In the spine and pelvis, MRI was comparable to (18)F-FDG PET/CT and (99m)Tc-MIBI in the detection of focal and diffuse disease, respectively. Because myelomatous lesions may often occur out of spinal and pelvic regions, MRI should be reserved to the evaluation of bone marrow involvement of these districts, whereas (18)F-FDG PET/CT can significantly contribute to an accurate whole-body evaluation of MM patients. Finally, whole-body (99m)Tc-MIBI, despite its limited capacity in detecting focal lesions, may be an alternative option when a PET facility is not available.