PET-CT reveals increased intestinal glucose uptake after gastric surgery.

BACKGROUND: Mechanisms of metabolic improvement after bariatric surgery remain incompletely understood. Intestinal glucose uptake is increased after gastric bypass in rodents, potentially contributing to reduced blood glucose and type 2 diabetes remission. OBJECTIVE: We assessed whether intestinal glucose uptake is increased in humans after gastric surgery. SETTING: University Hospital, United States. METHODS: In a retrospective, case-control cohort study, positron emission tomography-computerized tomography scans performed for clinical indications were analyzed to quantify intestinal glucose uptake in patients with or without history of gastric surgery. We identified 19 cases, defined as patients over age 18 with prior gastric surgery (Roux-en-Y gastric bypass [n = 10], sleeve gastrectomy [n = 1], or Billroth I [n = 2] or II gastrectomy [n = 6]), and 43 controls without gastric surgery, matched for age, sex, and indication for positron emission tomography-computerized tomography. Individuals with gastrointestinal malignancy or metformin treatment were excluded. Images were obtained 60 minutes after 18F-fluorodeoxyglucose injection (4.2 MBq/kg), and corrected by attenuation; noncontrast low-dose computerized tomography was obtained in parallel. Fused and nonfused images were analyzed; standardized uptake values were calculated for each region by volumes of interest at the region of highest activity. RESULTS: Both standardized uptake values maximum and mean were significantly increased by 41% to 98% in jejunum, ascending, and transverse colon in patients with prior gastric surgery (P < .05 versus controls). CONCLUSION: Intestinal glucose uptake is increased in patients with prior gastric surgery. Prospective studies are important to dissect the contributions of weight loss, dietary factors, and systemic metabolism, and to determine the relationship with increased insulin-independent glucose uptake and reductions in glycemia.

Kinetics of human brown adipose tissue activation and deactivation.

Brown adipose tissue (BAT) has been identified as a potential target in the treatment and prevention of obesity and metabolic disease. The precise kinetics of BAT activation and the duration of stimulus required to recruit metabolically active BAT, and its subsequent deactivation, are not well-understood. In this clinical trial, 19 healthy adults (BMI: 23.7 ± 0.7 kg/m2, Age: 31.2 ± 2.8 year, 12 female) underwent three different cooling procedures to stimulate BAT glucose uptake, and active BAT volume was determined using 18F-Fluorodeoxyglucose (FDG) PET/CT imaging. We found that 20 min of pre-injection cooling produces activation similar to the standard 60 min (39.9 mL vs. 44.2 mL, p = 0.52), indicating that BAT activity approaches its peak function soon after the initiation of cooling. Furthermore, upon removal of cold exposure, active BAT volume declines (13.6 mL vs. 44.2 mL, p = 0.002), but the deactivation process persists even hours following cessation of cooling. Thus, the kinetics of human BAT thermogenesis are characterized by a rapid increase soon after cold stimulation but a more gradual decline after rewarming. These characteristics reinforce the feasibility of developing mild, short-duration cold exposure to activate BAT and treat obesity and metabolic disease.

Mapping of human brown adipose tissue in lean and obese young men.

Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m2; 8 obese, BMI 34.8 ± 3.3 kg/m2] after 5 h of tolerable cold exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1-71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT-cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal-with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.

Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status.

BACKGROUND: In addition to its role in adaptive thermogenesis, brown adipose tissue (BAT) may protect from weight gain, insulin resistance/diabetes, and metabolic syndrome. Prior studies have shown contradictory results regarding the influence of thyroid hormone (TH) levels on BAT volume and activity. The aim of this pilot study was to gain further insights regarding the effect of TH treatment on BAT function in adult humans by evaluating the BAT mass and activity prospectively in six patients, first in the hypothyroid and then in the thyrotoxic phase. METHODS: The study subjects underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scanning after cold exposure to measure BAT mass and activity while undergoing treatment for differentiated thyroid cancer, first while hypothyroid following TH withdrawal at the time of the radioactive iodine treatment and then three to six months after starting TH suppressive treatment when they were iatrogenically thyrotoxic. Thermogenic and metabolic parameters were measured in both phases. RESULTS: All study subjects had detectable BAT under cold stimulation in both the hypothyroid and thyrotoxic state. The majority but not all (4/6) subjects showed an increase in detectable BAT volume and activity under cold stimulation between the hypothyroid and thyrotoxic phase (total BAT volume: 72.0 ± 21.0 vs. 87.7 ± 16.5 mL, p = 0.25; total BAT activity 158.1 ± 72.8 vs. 189.0 ± 55.5 SUV*g/mL, p = 0.34). Importantly, circulating triiodothyronine was a stronger predictor of energy expenditure changes compared with cold-induced BAT activity. CONCLUSIONS: Iatrogenic hypothyroidism lasting two to four weeks does not prevent cold-induced BAT activation, while the use of TH to induce thyrotoxicosis does not consistently increase cold-induced BAT activity. It remains to be determined which physiological factors besides TH play a role in regulating BAT function.

Activation of human brown adipose tissue by a ß3-adrenergic receptor agonist.

Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of ß3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a ß3-AR agonist currently approved to treat overactive bladder, to stimulate BAT as compared to placebo. Mirabegron led to higher BAT metabolic activity as measured via (18)F-fluorodeoxyglucose ((18)F-FDG) using positron emission tomography (PET) combined with computed tomography (CT) in all twelve healthy male subjects (p = 0.001), and it increased resting metabolic rate (RMR) by 203 ± 40 kcal/day (+13%; p = 0.001). BAT metabolic activity was also a significant predictor of the changes in RMR (p = 0.006). Therefore, a ß3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease.

Rifaximin suppresses background intestinal 18F-FDG uptake on PET/CT scans.

BACKGROUND: Identification of cancer or inflammatory bowel disease in the intestinal tract by PET/computed tomography (CT) imaging can be hampered by physiological uptake of F-fluorodeoxyglucose (F-FDG) in the normal colon. Previous work has localized this F-FDG uptake to the intestinal lumen, predominantly occupied by bacteria. We sought to determine whether pretreatment with an antibiotic could reduce F-FDG uptake in the healthy colon. PATIENTS AND METHODS: Thirty patients undergoing restaging PET/CT for nongastrointestinal lymphoma were randomly selected to receive rifaximin 550 mg twice daily for 2 days before their scan (post-rifaximin). Their PET/CT images were compared with those from their prior study (pre-rifaximin). Cecal maximum standard uptake value (SUVmax) and overall colonic F-FDG uptake were compared between scans. All PET/CT images were blindly scored by a radiologist. The same comparison of sequential scans was also undertaken in 30 patients who did not receive antibiotics. RESULTS: Thirty post-rifaximin scans were compared with 30 pre-rifaximin scans in the same patients. SUVmax in the cecum was significantly lower in the patient's post-rifaximin scans than in their pre-rifaximin scans (P=0.002). The percentage of scans with greater than grade 1 colonic F-FDG uptake was significantly lower in the post-rifaximin scans than in the pre-rifaximin scans (P<0.05). In contrast, there was no significant difference in the paired sequential scans from control patients, nor a reduction in the percentage of scans with greater than grade 1 colonic F-FDG uptake. CONCLUSION: This pilot study shows that treatment with rifaximin for 2 days before PET/CT scanning can significantly reduce physiological F-FDG uptake in the normal colonic lumen.

Quantification of human and rodent brown adipose tissue function using 99mTc-methoxyisobutylisonitrile SPECT/CT and 18F-FDG PET/CT.

UNLABELLED: For brown adipose tissue (BAT) to be effective at consuming calories, its blood flow must increase enough to provide sufficient fuel to sustain energy expenditure and also transfer the heat created to avoid thermal injury. Here we used a combination of human and rodent models to assess changes in BAT blood flow and glucose utilization. METHODS: (99m)Tc-methoxyisobutylisonitrile (MIBI) SPECT (n = 7) and SPECT/CT (n = 74) scans done in adult humans for parathyroid imaging were reviewed for uptake in regions consistent with human BAT. Site-directed biopsies of subcutaneous and deep neck fat were obtained for electron microscopy and gene expression profiling. In mice, tissue perfusion was measured with (99m)Tc-MIBI (n = 16) and glucose uptake with (18)F-FDG (n = 16). Animals were kept fasting overnight, anesthetized with pentobarbital, and given intraperitoneally either the ß3-adrenergic receptor agonist CL-316,243, 1 mg/kg (n = 8), or saline (n = 8) followed by radiotracer injection 5 min later. After 120 min, the mice were imaged using SPECT/CT or PET/CT. Vital signs were recorded over 30 min during the imaging. BAT, white adipose tissue (WAT), muscle, liver, and heart were resected, and tissue uptake of both (99m)Tc-MIBI and (18)F-FDG was quantified by percentage injected dose per gram of tissue and normalized to total body weight. RESULTS: In 5.4% of patients (4/74), (99m)Tc-MIBI SPECT/CT showed increased retention in cervical and supraclavicular fat that displayed multilocular lipid droplets, dense capillary investment, and a high concentration of ovoid mitochondria. Expression levels of the tissue-specific uncoupling protein-1 were 180 times higher in BAT than in subcutaneous WAT (P < 0.001). In mice, BAT tissue perfusion increased by 61% (P < 0.01), with no significant changes in blood flow to WAT, muscle, heart, or liver. CL-316,243 increased glucose uptake in BAT even more, by 440% (P < 0.01). CONCLUSION: Pharmacologic activation of BAT requires increased blood flow to deliver glucose and oxygen for thermogenesis. However, the glucose consumption far exceeds the vascular response. These findings demonstrate that activated BAT increases glucose uptake beyond what might occur by increased blood flow alone and suggest that activated BAT likely uses glucose for nonthermogenic purposes.

Sources of apical defects on a high-sensitivity cardiac camera: experiences from a practice performance assessment.

UNLABELLED: Apical perfusion artifacts seen on a high-sensitivity camera warranted a practice performance assessment to evaluate contributions from soft-tissue attenuation, patient positioning, and image processing techniques. METHODS: Cardiac perfusion studies (n = 534) spanning 5 mo were retrospectively reviewed. Images were acquired with the patient in the upright position, and attenuation correction was used. Regression analysis and contingency tables correlated clinical data to the presence of apical artifacts. RESULTS: There was a positive correlation of with female sex (χ(2) = 32, P < 0.001), degree of overlying soft tissues (χ(2) = 20, P < 0.002), and breast cleavage (χ(2) = 7, P < 0.008) and a negative correlation with angiography-confirmed disease (χ(2) = 6, P < 0.02). There was moderate interobserver agreement between 2 observers in determining the presence of apical defects (κ= 0.44, 95% confidence interval = 0.19-0.69), and there was a perceived improvement of apical defects using fewer iterative updates (χ(2) = 8, P < 0.003). CONCLUSION: An understanding of sources contributing to imaging artifacts is a crucial portion of quality assessment in radiology and nuclear medicine. A practice performance assessment study at our institution showed that apical artifacts on a new-generation cardiac camera can be partially attributed to overlying soft-tissue attenuation and ameliorated by altering the reconstruction.

Cold but not sympathomimetics activates human brown adipose tissue in vivo.

As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by (18)F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.

Focal physiologic fluorodeoxyglucose activity in the gastrointestinal tract is located within the colonic lumen.

AIM: Physiologic activity of 18F-fluorodeoxyglucose (FDG) in the intestinal tract occurs frequently in patients undergoing PET/computed tomography (CT) imaging, appearing most often in the colon. The purpose of this study is to determine the localization of the FDG within the colon. We hypothesize that intestinal FDG activity is intraluminal. METHODS: In a prospective Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, patients with physiologic colonic FDG activity on PET/CT scans were enrolled to undergo repeat imaging 2 h after stimulation of colonic motility with a high-fat meal. RESULTS: We identified 13 patients who had focal FDG activity in their colon during a routine clinical PET/CT scan. After administration of a high-fat meal, 10 patients (77%) demonstrated antegrade movement of FDG along the colon, consistent with luminal clearance. CONCLUSION: Our results suggest that normal physiologic FDG activity within the large intestine, seen on PET/CT scans, is intraluminal.

Respiratory gating enhances imaging of pulmonary nodules and measurement of tracer uptake in FDG PET/CT.

OBJECTIVE: The aim of this study was to evaluate prospectively the effects of respiratory gating during FDG PET/CT on the determination of lesion size and the measurement of tracer uptake in patients with pulmonary nodules in a clinical setting. SUBJECTS AND METHODS: Eighteen patients with known pulmonary nodules (nine women, nine men; mean age, 61.4 years) underwent conventional FDG PET/CT and respiratory-gated PET acquisitions during their scheduled staging examinations. Maximum, minimum, and average standardized uptake values (SUVs) and lesion size and volume were determined with and without respiratory gating. The results were then compared using the two-tailed Student's t test and the nonparametric Wilcoxon's test to assess the effects of respiratory gating on PET acquisitions. RESULTS: Respiratory gating reduced the measured area of lung lesions by 15.5%, the axial dimension by 10.3%, and the volume by 44.5% (p = 0.014, p = 0.007, and p = 0.025, respectively). The lesion volumes in gated studies were closer to those assessed by standard CT (difference decreased by 126.6%, p = 0.025). Respiratory gating increased the measured maximum SUV by 22.4% and average SUV by 13.3% (p < 0.001 and p = 0.002). CONCLUSION: Our findings suggest that the use of PET respiratory gating in PET/CT results in lesion volumes closer to those assessed by CT and improved measurements of tracer uptake for lesions in the lungs.

Identification and importance of brown adipose tissue in adult humans.

BACKGROUND: Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. METHODS: We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. RESULTS: Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007). CONCLUSIONS: Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.

Retrospective study of coronary uptake of 18F-fluorodeoxyglucose in association with calcification and coronary artery disease: a preliminary study.

OBJECTIVE: To determine whether focal 18F-fluorodeoxyglucose (FDG) uptake could be detected along the course of coronary arteries in patients with known coronary artery disease (CAD) and/or coronary artery calcification (CAC) by PET/computed tomography (CT) using a new patient preparation protocol that reduces background myocardial FDG uptake. MATERIALS AND METHODS: In this retrospective, Health Insurance Portability and Accountability Act-compliant study approved by our institutional internal review board, 60 FDG-PET/CT studies performed for noncardiac indications were reviewed and CAC and focal FDG uptake were determined. Cardiac histories were obtained. Age range was 21-88 years (64+/-16 years); 35 women/25 men; six had CAD documented by myocardial perfusion imaging, cardiac catheterization, or history of percutaneous coronary intervention or coronary artery bypass grafting. Chi-square probabilities were calculated. RESULTS: Fifteen of the 60 patients studied showed focal FDG uptake along the course of coronary arteries; fourteen of these showed significant CAC scores and four had documented CAD. The concordance of focal FDG coronary artery uptake was 58% with CAC, 77% with cardiac history, and 90% with extracardiac vascular focal FDG uptake. There were 20 focal FDG and coronary artery lesions in 15 patients and 11 of the 20 colocalized with calcification. No preferred anatomic location was found (junction, end of calcification or along coronary artery). CONCLUSION: This limited retrospective study shows that with a new patient preparation to reduce high FDG uptake by the myocardium on PET/CT scans, foci of increased FDG cardiac uptake can be seen in association with CAC and in patients with a history of CAD. These results provide initial evidence that it may be possible to use FDG-PET/CT to monitor sites of coronary plaque formation. Larger and invasive prospective studies will be necessary to fully determine the suitability of this technique for that purpose.

Method for decreasing uptake of 18F-FDG by hypermetabolic brown adipose tissue on PET.

OBJECTIVE: The purpose of this study was to determine whether use of a high-fat, very-low-carbohydrate protocol for preparing patients for PET decreases the frequency of (18)F-FDG uptake by hypermetabolic brown adipose tissue (BAT) on PET scans. MATERIALS AND METHODS: In this HIPAA-compliant retrospective study, 741 FDG PET/CT scans obtained during the winter months (October 1-April 30) for patients who prepared with a high-fat, very-low-carbohydrate, protein-permitted protocol were compared with 1,229 FDG PET scans obtained during the winter months for patients who prepared by fasting. FDG uptake on PET scans co-localized with regions of fat identified on the CT scans was assumed to represent hypermetabolic BAT. The categoric variables frequency of occurrence of hypermetabolic BAT (present or not) and the sex ratios of the groups before and after the change in preparation were compared by use of a chi-square test. The continuous variables of age and blood glucose level were compared by use of a two-tailed Student's t test. RESULTS: In this intention-to-treat analysis, there was no difference between the fasting (n = 1,229) and the high-fat, very-low-carbohydrate, protein-permitted diet (n = 741) groups in terms of age and sex. Patients who prepared with the high-fat diet had a significantly lower frequency of hypermetabolic BAT uptake on FDG PET scans during the winter months (p<0.0002) and had lower blood glucose levels (p<<0.001). CONCLUSION: In this intention-to-treat analysis, use of a high-fat preparation protocol significantly lowered the frequency of uptake of FDG by hypermetabolic BAT on FDG PET studies. Use of this protocol has the potential to decrease the rate of false-positive findings on oncologic FDG PET scans.

Suppression of myocardial 18F-FDG uptake by preparing patients with a high-fat, low-carbohydrate diet.

OBJECTIVE: Myocardial 18F-FDG uptake in PET scans in patients prepared by the usual fasting protocol may result in difficulties in interpretation because variable uptake may yield false-positive results regarding mediastinal abnormalities. We aimed to analyze, retrospectively, the effect of diet on myocardial FDG uptake. MATERIALS AND METHODS: The "fasting" group comprised 101 consecutive patients before a clinical change in the patient preparation protocol. The "new diet" group comprised 60 consecutive patients after the clinical protocol change who were directed to consume a very high-fat, low-carbohydrate, protein-permitted (VHFLCPP) diet before FDG injection. All patients were given a questionnaire that was used to verify diet adherence. Nonadherers or patients failing to complete questionnaires were excluded from analysis. Myocardial uptake was evaluated by measuring the maximum standardized uptake value (SUVmax) in areas defined by CT as being cardiac. RESULTS: The average SUVmax for the fasting group (n = 101) was 8.8 +/- 5.7, and the average SUVmax for the VHFLCPP group (n = 60) was 3.9 +/- 3.6. The one-tailed Student's t test yielded a p value of < 0.00001. CONCLUSION: A VHFLCPP meal eaten 3-6 hours before FDG injection suppresses myocardial FDG uptake. This should facilitate definition of mediastinal abnormalities on FDG PET, particularly with stand-alone PET. Furthermore, this patient preparation protocol may permit the detection of biologically active coronary artery disease.

Shareware program for nuclear medicine and PET/CT PACS display and processing.

OBJECTIVE: Many of the functions necessary for imaging and analyzing nuclear medicine studies are not available on radiology PACS. Over the past 20 years, we have developed a user-friendly, easily installed software package for nuclear medicine study analysis, display, Web access, and database storage and an integrated display for fused PET/CT. We are making this software available as free shareware that can be used without a license on any PC. The software package was developed as a cooperative effort between house and attending staff and our nuclear medicine programmer. Particular emphasis was put on making functions intuitive and user friendly. CONCLUSION: A shareware nuclear medicine PACS software package including a display for fused PET/CT studies has been developed, extensively clinically tested, and is freely available on the Internet.

Clinical pretreatment risk factors and Ga-67 scintigraphy early during treatment for prediction of outcome of patients with aggressive non-Hodgkin lymphoma.

BACKGROUND: Clinical pretreatment risk factors indicate the severity of disease in patients with aggressive non-Hodgkin lymphoma (NHL). Ga-67 scintigraphy during treatment is an early indicator of treatment-related features of lymphoma cells. The ability of risk factors and Ga-67 to predict disease outcome was compared in 139 patients with aggressive NHL. METHODS: Pretreatment clinical risk factors and Ga-67 scintigraphy performed after one cycle and at mid-treatment were evaluated for their correlation with response rate and as predictors of 5-year failure-free survival (FFS). Univariate analysis was performed to determine the ability of pretreatment risk factors and Ga-67 early during treatment to predict FFS. Subsequently, multivariate analysis was performed on the variables with significant univariate results using the Cox proportional hazards method. The predictive value of risk factors and Ga-67 scintigraphy was calculated to determine their suitability in selecting patients with poor outcome. RESULTS: Response rate correlated with stage of disease (P < 0.01) and the international prognostic index (IPI) score (P < 0.05). Five-year FFS was predicted by stage of disease (P < 0.004), performance status (P < 0.02), and the IPI score (P < 0.01). Response rate correlated with results of Ga-67 scintigraphy after one cycle of chemotherapy (P < 0.001) and at mid-treatment (P < 0.001). Five-year FFS was predicted by Ga-67 after one cycle of chemotherapy (P < 0.0004) and at mid-treatment (P < 0.0001). Positive Ga-67 after the first cycle of treatment predicted 64% of patients who had failure of treatment. A positive study at mid-treatment predicted 77% of patients who had treatment failure. Cox analysis showed Ga-67 after one course (P < 0.0012) and at mid-treatment (P < 0.0002) as being the most significant variables in predicting FFS. CONCLUSIONS: Ga-67 scintigraphy demonstrates early the effect of treatment in patients with aggressive NHL. It is a better predictor than pretreatment risk factors of both response rate and FFS. Positive Ga-67 early during treatment may be used as an independent test in selecting patients who will not respond favorably to current protocol treatment for early therapeutic modifications.