Isolation and partial characterization of a 67Ga-binding glycoprotein from Morris 5123C rat hepatoma.

A Glycoprotein, particularly high in tumors, has been extracted from Morris 5123C rat hepatomas and purified. The compound constitutes a major binding component for 67Ga in this hepatoma. It has a molecular weight of approximately 45,000. Its molecular weight was determined by sodium dodecyl sulfate:polyacrylamide gel electrophoresis and by Sephadex G-200 superfine gel filtration. The steps involved in its extraction and purification include ultrafiltration, gel filtration through Sephadex G-200 superfine, ion-exchange chromatography on diethylaminoethyl Sephadex A-50, and hydroxylapatite chromatography. The homogeneity of the compound was established by gel electrophoresis. The NH2-terminal residue, the percentage of nitrogen, the nonamino carbohydrate content, and the amino acid composition are reported.

The diagnostic utility of the lognormal behavior of PET standardized uptake values in tumors.

UNLABELLED: A meta-analysis of data primarily from PET oncologic investigations using FDG PET was performed. Its purpose was to establish statistical features of the distributions of standardized uptake values (SUVs) as possible aids in the diagnostic process. METHODS: We obtained 1536 values of oncologic markers from patient studies of 40 investigations in the literature. Statistical parameters were tabulated for analysis. RESULTS: A significant observation is that, unlike skewed SUV histograms, log10SUV has Gaussian behavior, which is not uncommon for biologic quantities. This was found for SUVs of FDG and 2 amino acids as well as a few other cancer markers. A possible model for explaining this is proposed. For FDG, the SD sigma of the log10SUVs for an average cancer category was 0.23. Examining data within the framework of the model points to physiologic factors as dominating SUV variability rather than PET protocols. When data for a single cancer category were available from multiple institutions, averages, mean(SUV)s, disagree beyond chance expectations. Diagnostic utility suggestions include a universal linear relationship between sensitivity and severity, defined as SUV/mean(SUV), on semilogarithmic probability paper; a generic receiver-operating-characteristic curve for all cancers; using [log10(mean(SUVmal)/mean(SUVnorm))] divided by (sigma(mal)2 + sigma(norm)2)(1/2) as a simple diagnostic effectiveness measure; and using Gaussian log10SUVs to avoid erroneous P values. CONCLUSION: Using the logarithms of markers, such as SUVs, several advantages stemming from their Gaussian nature can be achieved with benefits ensuing to the diagnostic process.

Ga-67 citrate imaging in tumors of the genito-urinary tract: report of cooperative study.

Whole-body imaging with Ga-67 citrate in 127 tumors of the genito-urinary tract has been evaluated by a cooperative group using a uniform protocol. Primary sites of tumor were not detectable by imaging, except for one bladder and one kidney tumor. Proven and apparent metastases yielded positive scans, however, in 51% of prostatic, 50% of bladder, 72% of kidney, and 53% of testicular neoplasms. In bladder and kidneys metastases, if bone sites are excluded, detection of soft tissue metastases was 61% and 75%, respectively. In embryonal-cell carcinoma of the testicle, 74% of metastatic foci were detected.

Ga-67 citrate imaging in malignant lymphoma: final report of cooperative group.

In a large cooperative study of Ga-67 uptake in non-Hodgkin's malignant lymphoma, 76% of untreated patients showed positive uptake in one or more lesions. The percentage of known individual lesions seen on scan was significantly lower; thus, negative findings at any one site may have much less significance than positive findings. After treatment, the number of lesions seen decreases sharply, but the role of Ga-67 in evaluating response to therapy is uncertain, especially in view of the fairly large number of lesions undetectable before therapy. Histologic type plays a role in Ga-67 uptake. Large lesions are much more effectively detected than small ones. In spite of numerous false-negative results, Ga-67 scanning is a useful method in evaluating the extent of untreated disease and the presence of lesions posttherapy.

Assessment of skeletal muscle viability by PET.

UNLABELLED: We investigated the use of [18F]fluoro-2-deoxyglucose (FDG) PET scanning for assessment of skeletal muscle viability in patients with peripheral vascular disease and in patients following free-flap skeletal muscle transfer for closure of open wounds. METHODS: We obtained 32 FDG-PET scans from 30 patients, either at the time of admission for peripheral vascular disease (n = 16) or between 1 and 15 days after surgery for skeletal muscle transfer (n = 16). Ratios between injured and contralateral limb FDG tracer activity uptake were correlated with clinical outcome at 1 mo to 3 yr follow-up. RESULTS: Viable muscle uptake ratios ranged from 0.47 to 7.88 (mean: 2.26 +/- 1.81; n = 26), while nonviable muscle uptake ratios ranged from 0.12 to 0.46 (mean: 0.27 +/- 0.12; n = 6; p < 0.02). After skeletal muscle transfer, two patients with viable tissue, as documented by PET, required amputation due to osteomyelitis, and one patient with peripheral vascular disease who showed viable tissue by PET required amputation 3 mo after the PET scan because of recurrent ulcers. CONCLUSION: FDG-PET scanning can determine skeletal muscle viability in patients with peripheral vascular disease and in patients following free-flap transfer.

Carbon-11-labeled amino acids for the rectilinear and positron tomographic imaging of the human pancreas.

Modification of the Bücherer-Strecker amino acid synthesis facilitated the production of DL-[11C]tryptophan and DL-[11C]valine for clinical trials in patients with proven or suspected pancreatic disease. Examples of rectilinear scans and tomographic images of the pancreas are presented in this initial paper. Positron computed tomography was done with the ORTEC ECAT system. Rapid localization of these C-11-labeled amino acids and fast clearance from the plasma permit almost immediate examination following i.v. injection. Illustrative images include the normal pancreas, pancreatitis, and pancreatic carcinoma. The use of positron tomobraphy with C-11-labeled DL-tryptophan and DL-valine appears to offer a new and promising diagnostic modality for the detection and study of pancreatic diseases.

Gallium-67 citrate imaging in Hodgkin's disease: final report of cooperative group.

A large cooperative study of Ga-67 uptake in Hodgkin's disease showed that 88% of untreated patients had a positive uptake in one or more lesions. The percent of individual lesions seen on scan, however, was significantly lower; this indicated that negative findings at any one site do not argue strongly against the possiblilty of a lesion there. After treatment, the number of visualized lesions decreased sharply, but the exact role of Ga-67 in evaluating therapy is still not clear. Of the various histologic types of Hodgkin's disease, there was a high incidence of localization in all except the lymphocyte-predominance type, which showed a slightly lower uptake. No lesions less than 1 cm in diameter were successfully imaged and the size most easily detected was 4 cm in diameter. As expected, the imaging technique was much less successful for abdominal lesions than for those at other sites because of interfering concentration in bowel and liver. Both radiotherpy and chemotherapy tend to reverse the abnormalities seen on scan. The finding of a significant number of unsuspected positive lesions in asymptomatic patients returning for routine followup suggests that this is a distinctly valuable use of Ga-67, allowing early therpy for recurrences.

Tumor location with 1-aminocyclopentane [11C] carboxylic acid: preliminary clinical trials with single-photon detection.

High specific activity [11C] Carboxyl-labeled 1-aminocyclopentane-carboxylic acid ([11C] ACPC) was tested as a tumor-scanning agent in thirty-eight patients. This artificial amino acid clears the blood to a level of less than 12% within 45 min; thus, imaging is possible within the useful life of C-11. [11C] ACPC can be produced in amounts adequate for clinical scanning. Doses between 12 and 45 mCi were given by i.v. injection, and scans obtained only in the single-photon mode gave clinical information on the sites of tumors. There was no evidence of any toxic effects from [11C] ACPC, and the radiation doses as extrapolated from animal data are approximately 0.01 rad per mCi for the whole body and less than 0.06 rad per mCi for the pancreas. In all but five of the 38 patients [11C] ACPC scans were compared with those obtained with Ga-67 citrate. There were 19 positive [11C] ACPC scans and 24 positive Ga-67 scans. The results indicate that [11C] ACPC is likely to be of diagnostic value for cancer patients if used in conjunction with positron tomography instrumentation.

Evaluation of fluorine-18-BPA-fructose for boron neutron capture treatment planning.

UNLABELLED: Boron neutron capture therapy (BNCT) using 4-[10B]boronophenylalanine-fructose (BPA-Fr) is in Phase II clinical trials to validate BNCT as a treatment for glioblastoma multiforme and melanoma. Successful BNCT depends on knowledge of the distribution of boron-containing agents in both tumor and normal tissue as currently determined by chemical confirmation of boron deposition in surgically removed malignant tissue before BNCT. METHODS: We used PET to noninvasively obtain in vivo information on the pharmacokinetics of the 18F-labeled analog of BPA-Fr in two patients with glioblastoma multiforme. Time-activity curves generated from the bolus injection of 18F-BPA-Fr were coinvolved to simulate a continuous infusion used for BNCT therapy. RESULTS: Distribution of 18F-BPA-Fr by PET was found to be consistent with tumor as identified by MR imaging. The 18F-BPA-Fr tumor-to-normal brain uptake ratio was 1.9 in Patient 1 and 3.1 in Patient 2 at 52 min after injection. The 18F-BPA-Fr uptake ratio in glioblastoma paralleled that of nonlabeled BPA-Fr seen in patients as previously determined by boron analysis of human glioblastoma tissue obtained from pre-BNCT surgical biopsy. CONCLUSION: Knowledge of the biodistribution of BPA-Fr enables pre-BNCT calculation of expected tissue dosimetry for a selected dose of BPA-Fr at a specific neutron exposure. Fluorine-18-BPA-Fr PET is capable of providing in vivo BPA-Fr biodistribution data that may prove valuable for patient selection and pre-BNCT treatment planning.

Linear least squares compartmental-model-independent parameter identification in PET.

A simplified approach involving linear-regression straight-line parameter fitting of dynamic scan data is developed for both specific and nonspecific models. Where compartmental-model topologies apply, the measured activity may be expressed in terms of: its integrals, plasma activity and plasma integrals--all in a linear expression with macroparameters as coefficients. Multiple linear regression, as in spreadsheet software, determines parameters for best data fits. Positron emission tomography (PET)-acquired gray-matter images in a dynamic scan are analyzed: both by this method and by traditional iterative nonlinear least squares. Both patient and simulated data were used. Regression and traditional methods are in expected agreement. Monte-Carlo simulations evaluate parameter standard deviations, due to data noise, and much smaller noise-induced biases. Unique straight-line graphical displays permit visualizing data influences on various macroparameters as changes in slopes. Advantages of regression fitting are: simplicity, speed, ease of implementation in spreadsheet software, avoiding risks of convergence failures or false solutions in iterative least squares, and providing various visualizations of the uptake process by straight line graphical displays. Multiparameter model-independent analyses on lesser understood systems is also made possible.

Sequential positron emission tomographic evaluations of brain metabolism in acute herpes encephalitis.

This first known positron emission tomography report on metabolic changes in acute herpes simplex virus (HSV-1) encephalitis demonstrates focal hypermetabolism in areas of cerebral cortex adjacent to actively inflamed hippocampus acutely infected with HSV-1. When neuropsychiatric symptoms recurred in a previously healthy 61-year-old patient 1 month after recovering from acute HSV-1 encephalitis, repeat positron emission tomography with fluorodeoxyglucose was helpful in ruling out recurrent active infection by showing marked hypometabolism throughout the previously infected temporal lobe.

Characterization of chest masses by FDG positron emission tomography.

Radiographic imaging techniques have proved to be of limited value in characterizing chest masses. Likewise, scintigraphic techniques with tumor-seeking single photon emitting agents have shown marginal practical benefit. In contrast, high resolution PET with [F-18]-2-fluoro-2-D-deoxyglucose (FDG) offers a unique opportunity to distinguish benign from malignant processes by determining metabolic characteristics. PET scan results, including graphical analysis of tumor transfer constants (Patlak plot) in 21 patients with primary lung cancer, were compared to clinical outcome (histologic proof or clinical follow-up of longer than 1 year) in 54 patients who had chest masses identified by CT and/or plain film. The patients were categorized into three groups. The first group (N = 23) had primary, unknown, lung masses. Differentiation of benign from malignant tumors by PET had a sensitivity of 100% and a specificity of 67%. The second group (N = 13) had proven lung carcinoma or lymphoma and post-therapy PET scanning for recurrent tumor. In this setting, PET had a sensitivity of 83% and a specificity of 80%. The third group (N = 18) had extrathoracic malignancies and suspected pulmonary metastases. Metastatic lesions were identified with a sensitivity of 87% and specificity of 83%. Glucose uptake by normal tissue is variable and inflammatory/infectious processes can have high FDG uptake and overlap with the glucose uptake of malignant tissue. FDG PET is useful in characterizing chest tumors based on the level of their metabolic activity. Malignant tissue has a high glucose uptake. Elevated FDG uptake by an active inflammatory process may produce overlapping results.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor detection with 1-aminocyclopentane and 1-aminocyclobutane C-11-carboxylic acid using positron emission computerized tomography.

Eight patients with proven or suspected neoplastic lesions were examined with 1-aminocyclobutane C-11-carboxylic acid and 1-aminocyclopentane C-11-carboxylic acid using positron emission computed tomography. The results of this comparative study have shown that both of these unnatural amino acids have a high affinity for malignant tumors. The potential of nonmetabolizable C-11-labeled amino acids as noninvasive indicators of metabolic tumor activity is demonstrated and discussed.

Differentiating benign from malignant lung lesions using "quantitative" parameters of FDG PET images.

UNLABELLED: Fluorine-18 labeled deoxyglucose positron-emission tomography (FDG-PET) applications in oncology include the differential diagnosis of chest masses and single pulmonary nodules. However, FDG is not tumor-specific; rather, it also accumulates in inflammatory processes. This study was performed to identify image parameters that would improve the specificity of PET. METHODS: Twenty-six patients who had benign and malignant lung lesions were examined retrospectively. Positron-emission tomography data were acquired in dynamic scanning mode after intravenous bolus of 250-402 MBq of FDG. Standardized uptake values (SUVs) were calculated and Patlak analyses were performed in selected regions of interest in the PET images. Positron-emission tomography results were related to histological diagnosis (N = 49) or clinical follow-up (N = 3). RESULTS: The specificity and sensitivity of the original PET scan reports, which was based on visual image interpretation and loosely applied SUVs, was 100% and 73%, respectively. Using the SUVs with a cut-off value of 3.8 and Kpat value with a cut-off at 0.025 min-1 improved the specificity to 81% and 85%. CONCLUSION: FDG-PET image interpretation can be facilitated by using SUV information or the accumulation rate of the radiotracer (Patlak). With additional validation, this method could have a significant cost-effective impact on the medical/surgical management of chest masses.

Pulmonary embolism. How V/Q scanning helps in diagnosis.

Ventilation-perfusion (V/Q) scanning is a useful predictor of pulmonary embolism. However, chest films and arterial blood gas studies are essential for proper interpretation of V/Q studies. The combination of clear, rapid reporting and good clinical judgment leads to improved management of patients in whom pulmonary embolism is suspected and avoids severe, life-threatening consequences.