Time sensitivity: a parameter reflecting tumor metabolic kinetics by variable dual-time F-18 FDG PET imaging.

OBJECTIVES: The aim of this study was to define and investigate the time sensitivity of tumors by variable dual-time fluorodeoxyglucose positron emission tomography (FDG PET). METHODS: Variable dual-time (t) protocol (P) FDG PET-computed tomography (CT) scans from 40 patients with pathologically proven head and neck tumors without brain metastasis were analyzed. The first protocol (P.I) consisted of 26 patients with early (E) and delayed (D) PET-CT obtained at 106 +/- 15 and 135 +/- 16 min after injection of 16.3 +/- 1.9 mCi FDG. The second protocol (P.II) recruited 14 patients with E- and D-PET performed at 54 +/- 13 and 151 +/- 28 min after injection of 9.6 +/- 1.7 mCi FDG. The maximum standardized uptake values (SUVs) were measured in the primary tumor (CA1) and the cerebellum (CBL). The time sensitivity (S) was defined as d{ln(SUV)}/d{ln(t)} and its value was obtained by linear regression of ln(D-SUV/E-SUV) vs ln(t (D)/t (E)). Patients with cerebellar variations greater than 30% in SUV between E- and D-PET was excluded from the analysis. RESULTS: Two patients from P.I were excluded due to wide cerebellar SUV variations. D-SUV were significantly higher than E-SUV in CA1 for both P.I (18.9 +/- 6.9 vs 14.8 +/- 5.6, p < 0.0005) and P.II (11.5 +/- 7.9 vs 9.7 +/- 6.9, p = 0.013). The S values for CA1 in P.I and P.II were 0.67 and 0.17, respectively. The D-SUV were also higher than E-SUV in CBL for both P.I (12.5 +/- 1.6 vs 11.6 +/- 1.6, p < 0.0005) and P.II (7.6 +/- 1.6 vs 7.0 +/- 1.6, p = 0.008). The S values for CBL in P.I and P.II were 0.47 and 0.04, respectively, which were over 1.4-fold smaller than that of CA1, suggesting fundamental kinetic differences between CA1 and CBL. CONCLUSIONS: The time sensitivity factor reflects another kinetic parameter of tumor metabolism besides SUV when using variable dual-time FDG PET. It offers another useful diagnostic tool in optimizing choices of dual-time protocols for oncologic PET-CT and in reducing SUV variations due to time interval differences with corrections using S.

CT-guided percutaneous cryotherapy of renal masses.

PURPOSE: To assess the results of initial and current techniques for percutaneous renal cryotherapy, including long-term imaging outcomes. MATERIALS AND METHODS: Computed tomography (CT)-guided percutaneous cryotherapy was performed on 49 masses in 48 outpatients and procedure comfort noted for each. These 49 masses included 36 primary renal cell carcinomas (RCCs), 3 oncocytomas, 1 angiomyolipoma, 6 renal inflammatory lesions, 2 benign parenchymal changes, and 1 colon cancer metastasis. All complications were graded according to standardized criteria. RESULTS: Patients received only local anesthesia and moderate sedation during the procedure and were discharged with minimal discomfort within 4-6 hours. All cryotherapy zones were well defined by CT during ablation as hypodense ice with an average diameter of 5.3 cm, covering an average tumor size of 3.3 cm. Average ablation zone diameters showed significant reduction over time (P < .001), becoming significantly less than the original tumor size by 12 months (P < .05). Major and minor complications were seen in 3 (6%) and 11 (22%) procedures, respectively. At a mean follow-up of 1.6 years (range, 1 week to 3.8 years) for primary RCC patients, four failures (11.1%) by imaging criteria were noted, but one proved to be inflammatory tissue at re-biopsy (estimated neoplastic failure rate = 3/36 = 8.3%). CONCLUSIONS: Percutaneous renal cryotherapy is a well-tolerated outpatient procedure that allows safe, CT monitoring of ice formation beyond visible tumor margins. With appropriate cryoprobe placements, a low failure rate appears less dependent on tumor size or location. Ablation volume involution was >80% after 6 months.

N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells.

Neuroblastoma is a peripheral nervous system tumor that accounts for 8-10% of all solid childhood tumors. N-Myc is the most reliable prognostic indicator for neuroblastoma. Bcl-2 is detected in 40-60% of primary neuroblastoma tumors and demonstrates anti-apoptotic action by conferring resistance to chemotherapy and radiation treatment. In neuroblastoma cell lines, the coexpression of N-Myc and Bcl-2 leads to increased tumorigenic properties. Matrix metalloproteinases (MMPs) are endopeptidases that degrade a wide range of basement membrane components, a process important for tumor invasion. This study investigates the effect of N-Myc and Bcl-2 on MMP expression and activation. MMP-2 expression and secretion are increased in SHEP neuroblastoma cells expressing Bcl-2 alone (SHEP/Bcl-2 cells) or both N-Myc and Bcl-2 (SHEP/N-Myc/Bcl-2 cells). MMP-2 activity is increased in the SHEP/N-Myc/Bcl-2 cells yet remains unchanged in SHEP/Bcl-2 cells. TIMP-2 expression is high in SHEP/Bcl-2 cells, which likely inhibits MMP-2 activity, and absent in SHEP/N-Myc/Bcl-2 cells, allowing MMP-2 activity. Invasion is increased in SHEP/N-Myc/Bcl-2 cells and prevented by the use of a pharmacologic MMP-2 inhibitor. These data imply that N-Myc and Bcl-2 cooperate to increase the expression, secretion, and activation of MMP-2, which likely leads to a more tumorigenic phenotype due to increased MMP-2 mediated invasion.