Investigating the existence of quantum metabolic values in non-Hodgkin's lymphoma by 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography.

OBJECTIVES: To investigate the existence of quantum metabolic values in various subtypes of non-Hodgkin's lymphoma (NHL). METHODS: Fifty-eight patients with newly diagnosed NHL and positron emission tomography (PET) performed within three months of biopsy were included. The standardized uptake value (SUV) from PET over the area of biopsy and serum glucose [Glc] were recorded. The group glucose sensitivity(G) for indolent and aggressive NHL was obtained by linear regression with ln(SUV) = G x ln[Glc] + C, where C is a constant for the group. Finally, the individual's glucose sensitivity (g) was obtained by g = {ln(SUV)-C}/ln[Glc], along with their means in various subtypes of NHL. To further investigate the influence of extreme [Glc] conditions, the SUVs corrected by the individually calculated g at various glucose levels, [Glc'] using SUV' =SUV x {[Glc']/[Glc]}(g), were compared to the original SUVs for both indolent and aggressive NHL. RESULTS: The averaged g (=G) for aggressive was significant different from that for indolent NHL (-0.94 +/- 0.51 vs. +0.13 +/- 0.10, respectively, p < 0.00005). There were significant differences in SUV for [Glc] < 80 or >110 mg/dl for both types of NHL. Unlike overlap among SUVs between NHL subtypes, the g value clearly categorized them into two distinct groups with positive (near-zero) and negative g values (around -1) for the indolent and aggressive NHLs, respectively. CONCLUSIONS: Distinct quantum metabolic values of -1 and 0 were noted in NHL. Aggressive NHL has a more negative value (or higher glucose sensitivity) than that of indolent and, thus, is more susceptible to extreme glucose variation.

Addressing glucose sensitivity measured by F-18 FDG PET in lung cancers for radiation treatment planning and monitoring.

PURPOSE: To address glucose sensitivity in lung cancers before and after radiation treatment (Tx). METHODS AND MATERIALS: Twelve patients were each studied with two pre-Tx positron emission tomography (PET) scans and 3 patients each with one post-Tx PET scan, with glucose concentration [Glc] and maximum standard uptake value (SUV) recorded. The pre-Tx glucose sensitivity, g from SUV1/SUV2= {[Glc]1/[Glc]2}g and Tx index, tau from SUVpost-Tx/SUVpre-Tx = {[Glc]post-Tx/[Glc]pre-Tx}tau was calculated by linear regression. Pre-Tx SUVs were corrected to post-Tx Glc with g (SUV'pre-Tx) for a pure Tx effect, R = ln(SUVpost-Tx/SUV'pre-Tx). RESULTS: There were no significant differences in SUV but [Glc] were different (96.4 +/- 10.9 vs. 88.3 +/- 10.5, p = 0.015) between two pre-Tx PET scans. Linear regression yielded g = -0.79 and tau = -1.78 to -2.41 (p < 0.0005 in all). The %DeltaSUV after Tx for 3 patients without vs. with g correction were different by -12%, 0%, and + 7%, suggesting varying effects from glucose. R values were also different and mean R (-0.81 +/- 0.38) was significantly different from zero (p = 0.03), consistent with successful Tx as confirmed by clinico-radiologic follow-up. CONCLUSIONS: The extra dimension of glucose sensitivity, g besides SUV incorporated in the combined Tx-derived tau may be a useful global Tx evaluation index even with differing [Glc].

Regional yttrium-90 microsphere treatment of surgically unresectable and chemotherapy-refractory metastatic liver carcinoma.

PURPOSE: The aim of this prospective study was to assess the safety and tumor response of intra-arterial Y-90 microspheres for the treatment of surgically unresectable and chemotherapy-refractory liver metastases. MATERIALS AND METHODS: Forty-six (46) patients with metastatic cancer to the liver from various solid tumors, with tumor progression despite polychemotherapy, were included. All patients had baseline computed tomography (CT), 18-Fluoro-2-deoxy-D-glucose-positron emission tomography (F-18 FDG-PET), hepatic angiography, and intra-arterial Tc-99m macroaggregated albumin (MAA) scan for the assessment of extrahepatic aberrant perfusion and lung shunting fraction. Twenty-seven (27) and 19 patients were treated with Y-90 glass- or resin-based microspheres (but not both), respectively, on a lobar basis and were monitored over 3 months after last treatment using dedicated attenuation corrected PET. For each patient, regions of interest (ROIs) were drawn along the liver edge to measure total liver standard uptake value (SUV) on axial images covering the entire liver for comparing pre- and post-treatment total liver SUV change. RESULTS: There was a significant decrement in total liver SUV after treatment by either glass- or resin-based microspheres (p = 0.0013 and 0.028, respectively). There was no significant difference in the amplitudes of the mean percentage reduction of tumor metabolism between these two agents (20% +/- 25% vs. 10% +/- 30% for glass- vs. resin-based microspheres; p = 0.38). None of the patients in the glass-based group developed complications, whereas 3 patients had complications related to hyperbilirubinemia (1 transient and 2 permanent) in the resin-based group. CONCLUSIONS: Results suggest that there is significant mean reduction of hepatic metastatic tumor load (metabolism), as evaluated objectively by PET after Y-90 microsphere, for the treatment of unresectable metastatic disease to the liver. The Y-90 therapy provides encouraging and safe results by arresting the progression of metastatic cancer to the liver with decreasing tumor metabolism.

Glucose-normalized standardized uptake value from (18)F-FDG PET in classifying lymphomas.

UNLABELLED: Our objective was to derive the best glucose sensitivity factor (g-value) and the most discriminating standardized uptake value (SUV) normalized to glucose for classifying indolent and aggressive lymphomas. METHODS: The maximum SUV obtained from (18)F-FDG PET over the area of biopsy in 102 patients was normalized by serum glucose ([Glc]) to a standard of 100 mg/dL. Discriminant analysis was performed by using each SUV(100) (SUV x {100/[Glc]}(g), calculated using various g-values ranging from -3.0 to 0, one at a time) as a variable against the lymphoma grades, and plotting the percentage of correct classifications against g (g-plot) to search for the best g-value in normalizing SUV(100) for classifying grades. To address the influence of the extreme glucose conditions, we repeated the same analyses in 12 patients with [Glc] < or = 70 mg/dL or [Glc] > or = 110 mg/dL. RESULTS: SUV(100) correctly classified lymphoma grades ranging from 62% to 73% (P < 0.0005), depending on the g-value, with a maximum at a g-value of -0.5. For the subgroup with extreme glucose values, the g-plot also revealed higher and more optimal discrimination at a g-value of -0.5 (92%) than at a g-value of 0 (83%) (P = 0.03). The discrimination deteriorated at g < -1 in both analyses. The box plot for all cases using a g-value of -0.5 showed little overlap in classifying lymphoma grades. For a visually selected threshold SUV(100) of 7.25, the sensitivity, specificity, and accuracy of identifying aggressive grades were 82%, 79%, and 81%, respectively. CONCLUSION: The results suggest that metabolic discrimination between lymphoma grades using a glucose-normalized SUV from (18)F-FDG PET is improved by introducing g-value as an extra degree of freedom.

Lymphatic mapping and sentinel node biopsy in women with an ipsilateral second breast carcinoma and a history of breast and axillary surgery.

BACKGROUND: Women with a history of breast and axillary surgery may demonstrate aberrant lymphatic drainage caused by disrupted lymphatic channels. Lymphoscintigraphy may be valuable in evaluation and staging of an ipsilateral second breast carcinoma. METHODS: We conducted a retrospective review of 16 women treated for a second ipsilateral breast carcinoma who underwent breast lymphoscintigraphy and intraoperative lymphatic mapping. Drainage patterns were compared with pathologic and operative findings. RESULTS: Lymphoscintigraphy succeeded in 69% of patients and demonstrated widely varied drainage patterns including ipsilateral axillary and supraclavicular as well as contralateral axillary and supraclavicular basins. No trend between successful lymphatic mapping and multiple clinical and pathologic measures was seen. CONCLUSIONS: In women with a second ipsilateral breast carcinoma and history of previous breast and axillary surgery, lymphoscintigraphy is feasible. Drainage patterns vary widely including across the midline of the thorax. Preoperative lymphoscintigraphy may be useful to ensure inclusion of potential sentinel nodes within the operative field.

Metabolic response after intraarterial 90Y-glass microsphere treatment for colorectal liver metastases: comparison of quantitative and visual analyses by 18F-FDG PET.

UNLABELLED: Our aim was to assess the feasibility of using PET for quantifying metabolic response after intraarterial (90)Y-glass microspheres for metastatic colorectal cancer to the liver by comparing visual estimates with hepatic standardized uptake values (SUVs). METHODS: Twenty-seven patients (15 men, 12 women; age, 68 +/- 12 y [+/-SD]) with metastatic colorectal cancer to the liver, and tumor progression despite polychemotherapy, were included. All patients had baseline CT or MRI, (18)F-FDG PET, hepatic angiography, and intraarterial (99m)Tc-labeled macroaggregated albumin scanning. Patients were treated with (90)Y-glass microspheres and were monitored for 3 mo using PET and serum carcinoembryonic antigen. The average absorbed dose was 139 +/- 22 Gy. All treatments were performed on a lobar basis. For each case analyzed, regions of interest were drawn along the liver edge to measure SUVs on maximum-intensity-projection (MIP) and resliced axial images. Concomitantly, the visual estimate was graded as +1, 0, -1, -2, or -3 for progression, no change, and mild, moderate, and dramatic improvement at posttreatment PET. RESULTS: Visual estimates placed 20 patients in the response category (-3 to -1) and 7 patients in the nonresponse category (0 to +1). There was a significant drop in the median SUV on the resliced axial images from 10,455 at baseline to 9,075 after treatment (P = 0.011) for the entire group. The percentage of metabolic response was significantly greater in the response group compared with that of the nonresponse group (-26% +/- 25% vs. +6% +/- 15%, P = 0.004). This correlated significantly with the respective visual estimates (r = 0.75, P < 0.0001). Furthermore, the direction of change agreed in 85% of patients using both methods. There was no significant correlation when the SUV from the simplified MIP images were used in the coronal or sagittal manner. CONCLUSION: It is feasible to quantify reduction of hepatic tumor metabolism objectively after (90)Y treatment for unresectable metastatic disease to the liver. SUVs of the entire axial slices of liver agree well with subjective visual evaluations. Quantitative PET is a useful technique in the treatment response evaluation of patients after (90)Y-glass microspheres.

Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody.

90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently approved for the treatment of relapsed or refractory low-grade, follicular, or CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates (111)In for imaging and (90)Y for therapy. Both health care workers and patients receiving this therapy need to become familiar with how it differs from conventional chemotherapy and what, if any, safety precautions are necessary. Because (90)Y is a pure beta-emitter, the requisite safety precautions are not overly burdensome for health care workers or for patients and their families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body weight and baseline platelet count; dosimetry is not required for determining the therapeutic dose in patients meeting eligibility criteria similar to those used in clinical trials, such as <25% lymphomatous involvement of the bone marrow. (111)In- and (90)Y-ibritumomab tiuxetan are labeled at commercial radiopharmacies and delivered for on-site dose preparation and administration. Plastic and acrylic materials are appropriate for shielding during dose preparation and administration; primary lead shielding should be avoided because of the potential exposure risk from bremsstrahlung. Because there are no penetrating gamma-emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely administered on an outpatient basis. Furthermore, the risk of radiation exposure to patients' family members has been shown to be in the range of background radiation, even without restrictions on contact. There is therefore no need to determine activity limits or dose rate limits before patients who have been treated with (90)Y radioimmunotherapy are released, as is necessary with patients who have been treated with radiopharmaceuticals that contain (131)I. Standard universal precautions for handling body fluids are recommended for health care workers and patients and their family members after (90)Y-ibritumomab tiuxetan administration. In summary, (90)Y-ibritumomab tiuxetan introduces (90)Y into clinical practice and expands the role nuclear medicine plays in the care of patients with cancer. Understanding the unique properties of this novel radioimmunoconjugate will facilitate its safe and effective use.

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.

A statistical investigation of normal regional intra-subject heterogeneity of brain metabolism and perfusion by F-18 FDG and O-15 H2O PET imaging.

BACKGROUND: The definite evaluation of the regional cerebral heterogeneity using perfusion and metabolism by a single modality of PET imaging has not been well addressed. Thus a statistical analysis of voxel variables from identical brain regions on metabolic and perfusion PET images was carried out to determine characteristics of the regional heterogeneity of F-18 FDG and O-15 H2O cerebral uptake in normal subjects. METHODS: Fourteen normal subjects with normal CT and/or MRI and physical examination including MMSE were scanned by both F-18 FDG and O-15 H2O PET within same day with head-holder and facemask. The images were co-registered and each individual voxel counts (Q) were normalized by the global maximal voxel counts (M) as R = Q/M. The voxel counts were also converted to z-score map by z = (Q - mean)/SD. Twelve pairs of ROIs (24 total) were systematically placed on the z-score map at cortical locations 15-degree apart and identically for metabolism and perfusion. Inter- and intra-subject correlation coefficients (r) were computed, both globally and hemispherically, from metabolism and perfusion: between regions for the same tracer and between tracers for the same region. Moments of means and histograms were computed globally along with asymmetric indices as their hemispherical differences. RESULTS: Statistical investigations verified with data showed that, for a given scan, correlation analyses are expectedly alike regardless of variables (Q, R, z) used. The varieties of correlation (r's) of normal subjects, showing symmetry, were mostly around 0.8 and with coefficient of variations near 10%. Analyses of histograms showed non-Gaussian behavior (skew = -0.3 and kurtosis = 0.4) of metabolism on average, in contrast to near Gaussian perfusion. CONCLUSION: The co-registered cerebral metabolism and perfusion z maps demonstrated regional heterogeneity but with attractively low coefficient of variations in the correlation markers.

Reduction of metastatic load to liver after intraarterial hepatic yttrium-90 radioembolization as evaluated by [18F]fluorodeoxyglucose positron emission tomographic imaging.

PURPOSE: To assess the response of hepatic metastases after treatment with intraarterial yttrium 90 radioembolization (ie, use of SIR-Spheres) with use of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). MATERIALS AND METHODS: Nineteen patients with metastatic cancer to the liver from various solid tumors with progression despite polychemotherapy were included. All patients underwent baseline computed tomography, FDG PET, hepatic angiography, and intraarterial technetium 99 m macroaggregated albumin scan for assessment of lung shunting fraction. Patients were treated with 90Y resin microspheres on a lobar basis and were monitored for 3 months with use of dedicated attenuation-corrected PET. For each patient, regions of interest were drawn along the liver edge to measure total liver standard uptake value (SUV) on axial images, covering the entire liver. Visual estimates were also performed and graded as +1, 0, -1, -2, or -3 for progression, no change, and mild, moderate, and dramatic improvement by posttreatment PET. RESULTS: The median absorbed dose for the tumor was 76 Gy. There was a significant overall decrease in total liver SUV after treatment (baseline, 71,134 +/- 38,055; after SIR-Sphere treatment, 59,941 +/- 26,509; P = .028) for the entire group. Visual estimates placed 15 patients (79%) in response categories (-3 to -1) and four patients (21%) in nonresponse categories (0 to +1) for the liver. The percentage change of total liver SUV after treatment in the response group (-19%) was significantly greater and different in direction than that in the nonresponse group (+27%; P = .03). This percentage change was also correlated significantly with the respective visual estimates (r = 0.72; P < .0005) for each individual patient. Three patients had major complications related to hyperbilirubinemia (transient, n = 1; permanent, n= 2). CONCLUSIONS: The results suggest that there is significant reduction of hepatic metastatic load as evaluated objectively by PET after 90Y radioembolization for the treatment of unresectable metastatic disease to the liver. 90Y radioembolization provides encouraging results by arresting progression of metastatic cancer to the liver.

Pulmonary Contusion in Contact Sports.

In brief Computed tomography (CT) is always more precise than chest x-ray for evaluating pulmonary contusions and other forms of lung trauma. CT is also valuable in guiding treatment for patients who have pulmonary contusions. As demonstrated by two case studies, not all sports-related pulmonary contusions are minor. Supportive treatment usually consists of maintaining the patient's oxygenation, treating associated injuries, and preventing complications.

An Unusual Stress Fracture Site: Midhumerus.

In brief A bodybuilder who reported left shoulder and upper arm pain was found to have a midhumeral stress fracture. Stress fractures are uncommon in non-weight-bearing bones, but a careful history that includes type, frequency, and duration of exercise can raise suspicion, and a physical examination, x-ray, and bone scan can detect the defects when they occur. Technetium bone scan can confirm injuries that are usually only suggested by x-rays.