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Unlabelled: The planning of research studies requires an understanding of the minimum number of subjects required. The aim of this study was to evaluate different methods of analyzing (18)F-fluoride PET ((18)F(-) PET) dynamic spine scans to find the approach that requires the smallest sample size to detect a statistically significant response to treatment., Methods: Eight different approaches to (18)F(-) PET analysis (3 variants of the Hawkins 3-tissue compartmental model, 3 variants of spectral analysis, deconvolution, and Patlak analysis) were used to evaluate the fluoride plasma clearance to bone mineral (K(i)). Standardized uptake values (SUVs) were also studied. Data for 20 women who had (18)F(-) PET spine scans at 0, 6, and 12 mo after stopping long-term bisphosphonate treatment were used to compare precision errors. Data for 18 women who had scans at baseline and 6 mo after starting teriparatide treatment were used to compare response to treatment., Results: The 4 approaches that fitted the rate constant k(4) describing the reverse flow of (18)F from bone as a free variable showed close agreement in K(i) values, with correlation coefficients greater than 0.97. Their %CVs were 14.4%-14.8%, and treatment response to teriparatide was 23.2%-23.8%. The 3 methods that assumed k(4) = 0 gave K(i) values 20%-25% lower than the other methods, with correlation coefficients of 0.83-0.94, percentage coefficients of variation (%CVs) of 12.9%-13.3%, and treatment response of 25.2%-28.3%. A Hawkins model with k(4) = 0.01 min(-1) did not perform any better (%CV, 14.2%; treatment response, 26.1%). Correlation coefficients between SUV and the different K(i) methods varied between 0.60 and 0.65. Although SUV gave the best precision (%CV, 10.1%), the treatment response (3.1%) was not statistically significant., Conclusion: Methods that calculated K(i) assuming k(4) = 0 required fewer subjects to demonstrate a statistically significant response to treatment than methods that fitted k(4) as a free variable. Although SUV gave the smallest precision error, the absence of any significant changes make it unsuitable for examining response to treatment in this study.

Unlabelled: (18)F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed K(i), reflects regional bone metabolism. The aim of this study was to compare the long-term precision of (18)F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo., Methods: Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent (18)F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the (18)F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (K(i-4k)), a 3k 3-compartmental model using nonlinear regression analysis (K(i-3k)), Patlak analysis (K(i-PAT)), and standardized uptake values., Results: With the exception of a small but significant decrease in K(i-3k) at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%-19%), 13.8% (10%-22%), 14.4% (11%-22%), and 26.6% (19%-40%) for K(i-3k), K(i-PAT), mean standardized uptake value, and K(i-4k), respectively. For comparison, the precision of the biochemical markers was 10% (7%-15%), 18% (13%-27%), and 14% (10%-21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for K(i-4k) to 0.85 for K(i-3k). No significant correlation was found between the repeated mean standardized uptake value measurements., Conclusion: The precision and intraclass correlation observed for K(i-3k) and K(i-PAT) was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of (18)F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.

Unlabelled: Quantitative studies of bone using (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) have a potentially valuable role in investigating the treatment of patients with metabolic bone disease. In this study we compared 3 different methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)) in 12 osteoporotic postmenopausal women (mean age, 67.3 y) before participation in a clinical trial of an osteoporosis therapy. The aim was to compare the consistency and accuracy of the 3 methods before their use in evaluating the subjects' response to treatment., Methods: Subjects were injected with 600 MBq (99m)Tc-MDP and 3 MBq (51)Cr-ethylenediaminetetraacetic acid ((51)Cr-EDTA) and whole-body bone scan images were acquired at 10 min, 1, 2, 3, and 4 h. Two-minute static images of the thighs were acquired immediately after the 1- to 4-h whole-body scans. Six blood samples were taken between 5 min and 4 h, and free (99m)Tc-MDP was measured using ultrafiltration. The glomerular filtration rate (GFR) was estimated from the (51)Cr-EDTA plasma curve. The methods used to evaluate K(bone) were (a) the area-under-the-curve (AUC) method, in which the GFR measurement was subtracted from the total (bone plus renal) clearance (K(total)) measured from the free (99m)Tc-MDP plasma curve; (b) the modified Brenner method, in which (99m)Tc-MDP renal clearance estimated from the whole-body counts was subtracted from the total clearance measured from the rate of elimination of tracer from soft tissue; and (c) the Patlak plot method, which was also used to derive regional values of K(bone) for the skull, spine, pelvis, arms, and legs., Results: There was good agreement between the 3 methods of measuring K(bone). (mean K(bone) +/- SD: AUC method, 30.3 +/- 6.4 mL x min(-1); Brenner method, 31.1 +/- 5.8 mL x min(-1); Patlak method, 35.7 +/- 5.8 mL x min(-1)). The correlation coefficients between the methods varied from r = 0.767 (P = 0.004) to r = 0.805 (P = 0.002). Regional measurements of (99m)Tc-MDP clearance gave the following percentages of the whole-skeleton clearance: skull, 13.3%; spine, 16.6%; pelvis, 17.2%; arms, 11.1%; legs, 23.7%., Conclusion: The 3 methods gave consistent and accurate measurements of K(bone). The Patlak method can be used to study regional as well as total-skeleton values of K(bone).

Unlabelled: Plantar fasciitis is a common cause of foot pain and may be disabling. Although localized injection is painful, anesthetics or corticosteroids can relieve symptoms well. Bone scintigraphy can confirm the diagnosis. We hypothesized that blood-pool abnormalities could provide prognostic information on the response to such injections., Methods: We devised scintigraphic criteria that graded the blood-pool abnormalities as being localized to the plantar enthesis, being localized to half the length of the aponeurosis, or involving the whole aponeurosis. We evaluated 24 patients with an established diagnosis of plantar fasciitis, 8 of whom had bilateral disease, leading to a total of 32 feet injected., Results: After injection, pain was relieved either completely or nearly completely in 20 feet. The other 12 feet had short-term or no improvement, with persistent pain and loss of function at 4-5 wk after injection. Of the 20 feet responding to injection, 14 had focal hyperemia on blood-pool images and 6 had minimal extension into the proximal third of the plantar soft tissues. No patient with diffuse hyperemia in the plantar fascia had a response (5/12 feet). On the delayed images of the 20 responders, mild inferior calcaneal uptake was seen in 8 feet, moderate uptake in 6, and severe uptake in 6. These groups did not significantly differ (P > 0.05). The blood-pool studies had good reproducibility, with a kappa-value of 0.64., Conclusion: Critical evaluation of plantar blood-pool images provides prognostic information on the response to localized injection into the enthesis. Reporting such studies is simple and reproducible.

Unlabelled: Quantitative studies of bone using (99m)Tc-methylene diphosphonate (MDP) reflect bone remodeling. The simplest method of evaluating (99m)Tc-MDP kinetics involves taking multiple blood samples and measuring total clearance (K(total)) from the area under the plasma curve (AUC) and deriving bone clearance (K(bone)) by subtracting glomerular filtration rate (GFR) from K(total). However, the accuracy of the AUC method is uncertain because of assumptions that the terminal exponential is reached by 2 h and that the rate constant k(4), representing the backflow of tracer from bone to plasma, is negligibly small. The aim of this study was to validate the accuracy of the AUC method by comparing K(bone) values obtained by that method with those obtained by gamma-camera imaging., Methods: Seventy-one patients were injected with 600 MBq of (99m)Tc-MDP. For the first 22 patients, whole-body images were acquired at 15 min and at 1, 2, 3, and 4 h after injection, whereas the remaining 49 were imaged at 15 min and at 1 and 3 h. Two-minute static images of the thighs were acquired immediately before each whole-body scan. Multiple blood samples were taken between 5 min and 4 h, and free (99m)Tc-MDP was measured using ultrafiltration. Two gamma-camera methods were used to evaluate K(bone): the Patlak plot method and the Brenner method, which is based on measuring soft-tissue uptake in the thighs. The soft-tissue data were also used to measure k(4)., Results: The soft-tissue data gave a k(4) value of 0.0003 min(-1) (95% confidence interval, 0-0.0008 min(-1)). The mean (+/-SD) (99m)Tc-MDP K(bone) was 56.0 +/- 32.4 mL x min(-1) with the AUC method, 49.5 +/- 32.1 mL x min(-1) with the Patlak method, and 42.8 +/- 32.0 mL x min(-1) with the Brenner method. Correcting the AUC values of K(total) by factors of 0.95 and 0.90 gave K(bone) values in agreement with the Patlak and Brenner methods, respectively., Conclusion: Values of k(4) are too small to affect values of K(bone) measured using the AUC method. Correcting K(total) by factors in the range of 0.90-0.95 corrects for the error in the terminal exponential and brings K(bone) values measured using the AUC method into agreement with the gamma-camera results.

Unlabelled: Quantitative studies of the kinetics of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) in metastatic and metabolic bone disease require the measurement of free tracer in plasma to derive the input function. Several methods of measuring free (99m)Tc-MDP have been described including ultrafiltration, precipitation using trichloroacetic acid, and a direct in vivo measurement based on the assumption that free MDP is cleared through the kidneys by glomerular filtration. The aim of this study was to validate ultrafiltration as a convenient and accurate method of measuring the free fraction of (99m)Tc-MDP by comparing it with the glomerular filtration rate (GFR) method. A second aim was to measure the percentage of free (99m)Tc-MDP in a cross-section of patients using ultrafiltration to determine the interpatient variability and, therefore, whether individual measurements are required for bone kinetic studies., Methods: In study 1, 10 volunteers (7 women, 3 men; mean age, 37 y; range, 26-55 y) were injected with 3 MBq (99m)Tc-MDP and 3 MBq (51)Cr-ethylenediaminetetraacetic acid, and multiple blood and urine samples were taken between 0 and 4 h. Plasma samples were spun in 5-, 10-, and 30-kDa filters and counted in a gamma-counter. In study 2, 51 randomly selected patients (26 women, 25 men; mean age, 66 y; range, 31-87 y) attending our department for a routine bone scan were injected with 600 MBq (99m)Tc-MDP, and 4 blood samples were taken between 0 and 4 h and spun in 10-kDa filters., Results: In study 1, the mean percentages (+/-SD) of free (99m)Tc-MDP at 5 min and 4 h after injection measured using the 10-kDa filters were 83.1% +/- 3.4% and 44.0% +/- 10.0%. The mean ratios (+/-SEM) of the free (99m)Tc-MDP in ultrafiltrate compared with the GFR method for the 5-, 10-, and 30-kDa filters were 0.894 +/- 0.010, 0.943 +/- 0.009, and 0.987 +/- 0.010. In study 2, the mean percentages (+/-SD) of free (99m)Tc-MDP at 15 min and 4 h were 75.3% +/- 8.0% and 48.8% +/- 9.5%, with a precision error of 2.3%. The percentages of free MDP at 150 min and 4 h were significantly correlated with GFR but not with serum albumin., Conclusion: Ultrafiltration provides an accurate method of evaluating free (99m)Tc-MDP in plasma for bone kinetic studies. The results from both the healthy volunteers in study 1 and the patients in study 2 show that protein binding varied with time and showed significant differences between individuals that were partly dependent on GFR. It is thus necessary to measure individual protein binding values for bone kinetic studies.

Unlabelled: Quantitative radionuclide studies of bone using the short-lived tracers (18)F-fluoride and (99m)Tc-methylene diphosphonate (MDP) are an alternative method to biochemical markers of bone turnover for investigating the dynamic state of the skeleton. In this study we evaluated their use to quantify bone turnover in women receiving antiresorptive therapy compared with that of untreated control subjects., Methods: The patients were 69 healthy postmenopausal women. Twenty-six women were receiving hormone replacement therapy (HRT) and 43 were untreated age-matched control subjects. After bolus injection of (18)F-fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid (3 MBq), and (125)I-labeled human serum albumin (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h. The clearance to bone mineral K(bone) was first evaluated using the area under the plasma concentration curve (AUC) on the assumption that the rate constant k(4) for the outflow of tracer from bone was negligibly small. AUC values of K(bone) were then compared with those found using a compartmental model method that allowed k(4) to be fitted as a free parameter., Results: Using the AUC method the mean plus minus SD for K(bone) for the 2 tracers were: (18)F-fluoride, 61.8 plus minus 12.0 mL center dot min(-1) (HRT group) versus 67.2 plus minus 12.6 mL center dot min(-1) (control group) (P = 0.045); and (99m)Tc-MDP, 40.3 plus minus 8.2 mL center dot min(-1) (HRT group) versus 44.2 plus minus 7.6 mL center dot min(-1) (control group) (P = 0.024). Values for the 2 tracers in individual patients were moderately well correlated (r = 0.76; P < 0.001). Using the compartmental model method, k(4) for (18)F-fluoride was shown to lie in the range 0--0.0025 min(-1) with a best-fit value of 0.0018 min(-1). Values of K(bone) determined using k(4) = 0.0018 min(-1) were highly correlated with the AUC values (r = 0.989; SEE = 2.05 mL center dot min(-1)) with numeric values that were larger by a factor of 1.53. Analysis of the (99m)Tc-MDP data was more difficult because of uncertainties in protein binding in the extracellular fluid compartment space. The best fit for k(4) was in the range 0.0010--0.0014 min(-1) with values of K(bone) similar to those found using the AUC method., Conclusion: Values of K(bone) determined using the AUC method were able to differentiate between HRT-treated women and postmenopausal women who were not treated and were highly correlated with those determined using a compartmental model method with nonzero values of k(4).

From 1990 to 2000, several effective new treatments were introduced for the prevention of osteoporotic fractures; these treatments were proven effective in large, international, clinical trials. At the same time, there was rapid technologic innovation, with the introduction of new radiologic methods for the noninvasive assessment of patients' bone density status. These developments led to the publication of guidelines for the clinical use of bone densitometry that include criteria for the referral of patients for investigation as well as recommendations for intervention thresholds for the initiation of preventive treatment of osteoporosis. Dual-energy x-ray absorptiometry scanning of the spine and hip remains the technique of choice for bone densitometry studies, although there is now a wider appreciation of the need for smaller, cheaper devices for scanning the peripheral skeleton if the millions of women most at risk of a fragility fracture are to be identified and treated. This article reviews these developments, concentrating in particular on the advantages and disadvantages of the different types of equipment available for performing bone densitometry investigations, the guidelines for the referral of patients, and the principles for the interpretation of the scan findings.

Unlabelled: Technetium-99m HL91 is a potential agent for imaging hypoxic tissue in vivo. A pilot evaluation using a prototype formulation assessed efficacy in tumor imaging and compared results with 18F-fluorodeoxyglucose (FDG) PET., Methods: Ten patients with malignant tumors were included. Tumors included carcinoma of the bronchus (n = 3), carcinoma of the thyroid (n = 2), lymphoma (n = 2), soft tissue sarcoma (n = 1), carcinoid (n = 1) and carcinoma of the breast (n = 1). Whole-body planar scans and localized SPECT scans were performed at 1 and 4 hr postinjection of 600 MBq 99mTc HL91. Half-body and localized emission/transmission 18F-FDG PET scans were performed 60 min postinjection 370 MBq 18F-FDG in eight patients. Lesion-to-normal tissue background ratios were measured for all 99mTc HL91 and 18F-FDG PET scans and percentage uptake and standardized uptake values measured for 99mTc HL91 and 18F-FDG PET, respectively., Results: Technetium-99m HL91 showed visible uptake into the tumor area in all seven studies where the tumor was clearly identified by 18F-FDG PET; 99mTc HL91 uptake was not detected in one study (carcinoid) in which 18F-FDG was weakly positive. Two further tumors, in which PET correlation was not available, showed accumulation of 99mTc HL91. In two 99mTc HL91 studies, abnormality was apparent only on SPECT images. Lesion-to-normal tissue background ratios for 99mTc HL91 ranged from 1.22/2.53 at 1 hr and 1.33/2.89 at 4 hr on planar images and 1.23/5.2 and 1.67/14.6 on SPECT images, respectively., Conclusion: In this study, the use of 99mTc HL91 resulted in uptake in the majority of malignant tumors identified by 18F-FDG-PET. Technetium-99m HL91 exhibits good imaging characteristics, with imaging at 4 hr providing good lesion-to-normal tissue background ratios, that are further enhanced by SPECT.

Unlabelled: Paget's disease of bone is common in the elderly and is associated with increased osteoblastic and osteoclastic activity at affected sites in the skeleton. It is not known whether this high metabolic activity is associated with increased glycolysis and, hence, uptake of [18F]FDG. The appearances of Paget's disease with [18F]FDG PET have not been described and it is not known whether Paget's may cause false-positive studies in those undergoing oncological staging or whether [18F]FDG PET can reliably differentiate benign pagetic change from osteosarcoma that may complicate Paget's disease. We reviewed [18F]FDG PET scans in patients with uncomplicated Paget's disease and documented its appearances., Methods: Eighteen patients with established Paget's disease and typical radiological features had 99mTc-MDP bone scans and [18F]FDG PET scans performed. Serum alkaline phosphatase (ALP) was also measured., Results: All patients showed high uptake of MDP in affected bones. Of the 18 patients only six showed any uptake of [18F]FDG. This occurred in some but not all bones shown to be involved on MDP bone scans. Three patients demonstrated low-grade uptake and three showed marked accumulation of [18F]FDG. The [18F]FDG-positive group had higher serum ALP levels than the [18F]FDG-negative patients (p < 0.05)., Conclusion: Paget's disease of bone is not associated with abnormal [18F]FDG uptake in the majority of patients and, therefore, there is potential for discriminating between benign Paget's disease and associated Paget's sarcoma. However, low-grade uptake may be seen in patients with more active disease as measured by ALP. Rarely, marked uptake of [18F]FDG may be seen and Paget's disease should be included as a possible cause of false-positive scans in elderly patients who are being assessed for metastatic disease.

Unlabelled: This retrospective analysis of SPECT bone scans of the knee was undertaken to define typical bone scan appearances and to assess the sensitivity of this method. We looked at 14 patients, mostly with chronic knee pain, who had anterior cruciate ligament (ACL) tears detected by MRI., Method: Of the 14 patients, 10 were referred for bone scanning following injury and 4 complained of chronic knee pain without injury. Planar scans were performed 4 hr after the injection of 750 MBq of 99mTc-MDP. Tomographic images were obtained by a 64 x 20-sec acquisition over 360 degrees using a high-resolution collimator. MRI imaging included axial and sagittal, T1 weighted and coronal fast field echo (FFE) sequences. Ten patients also had arthroscopy performed., Results: MRI scans showed 6 lone ACL tears and 8 combined with other ligamentous injuries. SPECT scans showed abnormalities in 10 patients in the region of ACL insertions but only 4 planar studies were abnormal. SPECT identified focal activity at the upper (n = 8) or lower (n = 2) insertion of the ACL. Six of 10 arthroscopies confirmed ACL tears, 2 complete and 4 partial. Overall, agreement was found with MRI in 10 of 14 cases and in 8 of 10 with arthroscopy. Abnormalities were identified in 10 of 11 regions of other ligament or bone injury identified by MRI., Conclusion: SPECT bone scanning of the knee is superior to planar imaging in detecting ACL injury and is a sensitive technique. Focal activity may be seen at either end of ACL attachment but more commonly at the upper femoral insertion. Knee SPECT may be a valuable examination in suspected ACL injury, particularly if MRI is not available, is equivocal or where clinical signs are absent.

Two children (aged 12 and 14 yr) with a history of complex congenital heart disease presented with symptoms and signs suggestive of pulmonary embolism. Initial ventilation-perfusion lung scans showed normal, approximately equal ventilation to both lungs. Global reduction of perfusion to the right lung was observed in one and was observed in the left lung in the other patient. It was not possible to exclude a large, central embolus in either case. Due to complex cardiac anatomy, however, which included bilateral cavopulmonary anastomoses in the first patient and SVC-right pulmonary artery and right atrial-pulmonary artery anastomoses in the second, repeat scans were performed within a short period in each case with different injection sites, including the contralateral arm and a leg injection, respectively. In both patients, these follow-up scans showed a different perfusion agent distribution to each lung when compared to the initial scans. These results demonstrated that there was no evidence of pulmonary embolism in either case.

Bone scanning provides a functional assessment of skeletal pathology not available with conventional radiography or special radiographic techniques such as CT and MRI. Bone scanning detects osteoblastic activity associated with many forms of orthopedic skeletal disease. Several of the more common orthopedic applications of bone scanning have been described above, while equally important topics such as prothesis loosening, avascular necrosis, and the reflex sympathetic dystrophy syndrome were not considered. Thus, for a great range of benign skeletal pathology, bone scanning can provide the orthopedic surgeon with practical information concerning the cause of the patient's pain, the true significance of otherwise questionable radiographic findings, the extent of disease and the results of orthopedic surgical treatment.

Pamidronate is one of several powerful bisphosphonates able to produce prolonged remissions of Paget's disease. This study examined to what extent bone scan changes parallel the clinical response and whether there is variability in the behavior of individual lesions. Twenty-five patients with pagetic bone pain for more than 2 yr were examined with bone scintigraphy before and on average 8 mo after six 30-mg infusions of pamidronate given weekly. Serum alkaline phosphatase and urinary hydroxyproline-to-creatinine ratios were measured before and 6 mo after treatment. A second course of pamidronate was given to 13 patients who had clinical or biochemical relapse. Of 136 pagetic lesions, 13 (10%) completely resolved, 90 (65%) improved and 33 (24%) remained unchanged. There was no significant difference in response between bony sites, although less active lesions were more likely to resolve completely. In conclusion pamidronate has a powerful effect on bone scan appearances in Paget's disease. Most lesions improve but complete resolution is uncommon. Less active lesions are more likely to resolve and are less likely to require further therapy.

The presence of the "hot patella" sign was evaluated in a prospective study of 200 consecutive bone scans, and in a review of scans from 148 patients with various metabolic bone disorders and 61 patients with lung carcinoma. The incidence was found to be 31%, 26% and 31% respectively. This sign is an extremely common scan finding and may be seen in association with a wide variety of disorders. It is concluded that this sign cannot be considered to be of diagnostic value.

Measurement of 24-hr whole-body retention of Tc-99m HEDP, using a shadow-shield, whole-body monitor, has been shown to be a sensitive measure of skeletal metabolism and of value in the diagnosis of metabolic bone disease. A new method of measuring the retention using a gamma camera, with a scanning (fishtail) collimator and patient placed at 2.,3 m distance, has been evaluated in 18 patients undergoing routine bone scans. The patients also had whole-body monitor (WBM), and the two methods correlated well, yielding a regression line GC% = -0.82 + 0.98 WBM%, r = 0.975, p less than 0.001. The limitations to, and repeatability of, the gamma-camera measurements are discussed. This work shows that measurements of whole-body retention can be obtained in any nuclear medicine department possessing a gamma camera with a suitable collimator.

We report our experience using [131I]metaiodobenzylguanidine (MIBG) to image nine patients with proven medullary carcinoma of the thyroid (MCT). Positive uptake was seen in four patients, equivocal uptake in one patient, and no uptake in four patients. Data is presented to demonstrate the pharmacokinetics of [131I]MIBG in three of the patients studied. Two patients, with diarrhea and severe pain from known bone metastases and positive uptake on [131I]MIBG diagnostic scanning, subsequently received therapeutic doses of [131I]MIBG, with marked improvement in both pain and diarrhea, but no evidence of significant biochemical response. Iodine-131 MIBG uptake in patients with MCT is variable, and gives a higher false-negative rate than is found when using [131I]MIBG to image other neuroectodermally derived tumors. The therapeutic potential of [131I]MIBG in patients with MCT warrants further evaluation, in view of the symptomatic relief experienced following therapy doses in two patients with extensive disease.

Baseline staging bone scans in 1,267 consecutive women with breast cancer attending a single clinic between 1980 and 1986 were reviewed. 0.3% of patients with T1, 3% with T2, 8% with T3, 13% with T4 tumors and none of those with Stage 1, 3% with Stage 2, 7% with Stage 3, and 47% with Stage 4 disease had a positive scan due to bone metastases. Two hundred eight-nine (23%) had bone scan abnormalities secondary to radiologically confirmed benign bone disease. In 20 patients, no cause for a bone scan abnormality could be found after a median follow-up of 3.50 yr, a false-positive frequency of 1.6%. The false-negative rate was 0.08%. It is concluded that patients with tumors less than 2 cm are most unlikely to have a positive scan. In this instance, scans are not required routinely. However, we recommend a baseline scan in all patients with Stage 2, 3, or 4 disease.

The bone scan findings of 160 consecutive cases of breast cancer metastatic to bone presenting to Guy's Hospital between 1982-1987 were retrospectively assessed for number and distribution of lesions. Twenty-one percent of patients relapsed with a solitary bone metastasis. The spine was the commonest site for both solitary (52% of cases) and multiple (87%) metastases. Solitary bone metastases are more common than previously thought.

Twenty normal volunteers had measurements of 24-hr whole-body retention (WBR) of three structurally related Tc-99m-labeled phosphonate skeletal imaging agents: (1-hydroxyethylidene) diphosphonate (HEDP), methylene diphosphonate (MDP), and hydroxymethylene diphosphonate (HMDP). The average WBR values, reflecting skeletal uptake, were 18.4, 30.3, and 36.6%, respectively. These results clearly illustrate that slight alterations in diphosphonate molecular structure have a significant effect upon specificity for osseous tissue, and thus may affect skeletal image quality and the usefulness of the WBR technique in diagnosing metabolic bone disease.

We have compared bone scintigrams made with Tc-99m-tagged HEDP (1-hydroxyethylidene diphosphonate)and MDP (methylene diphosphonate), the former at 4 hr after injection, the latter at both 2 and 4 hr. In 17 patients with skeletal metastases, there was no significant difference in lesion count or scan quality between the 4-hr images. The tumor-to-bone ratio (T/B) was significantly higher with Tc-HEDP (p less than 0.02). Lesion detection rate and T/B ratios were both lower with Tc-MDP at 2 hr when compared with the 4-hr values for both Tc-HEDP (p less than 0.02, p less than 0.005) and Tc-MDP (p less than 0.02, p less than 0.01). The 4-hr Tc-MDP scan was of significantly higher quality than the 2 hr Tc-MDP scan (p less than 0.01). Although Tc-HEDP produces a higher T/B ratio at 4 hr, the present study does not suggest that either agent is superior in clinical practice.

Bone scans in three patients showed generalized symmetrical increased uptake of radiopharmaceutical by the skeleton and absent or faint kidney images. It is thought that these appearances may be attributable to excess vitamin D, but other possible contributing factors, including the presence of renal osteodystrophy, are discussed.

The presence of eight "metabolic features" was assessed on the bone scintigrams of ten patients with osteomalacia. In all of these bone images, sufficient features were present to strongly suggest a metabolic disorder. There scintiphotos were included in a controlled blind study using 30 normal bone scans and 20 scans of metastatic disease. Nine of the ten metabolic bone images were correctly identified by two independent observers. Skeletal uptake of radiotracer, expressed as bone-to-soft tissue ratio, was significantly higher in the osteomalacic patients than in a group of 80 controls.

Digital bone scintigrams were obtained in 19 patients using Tc-99m hydroxyethylidene diphosphonate (HEDP). These were quantitated for skeletal, soft-tissue and renal uptake of tracer using a contrast-enhancement technique to define the regions of interest. Twenty-four hr whole-body retention (WBR) of HEDP was also measured. It was found that approximately 70% of retained diphosphonate was localized in the skeleton at 24 hr, with 26% in soft tissue and 4% in kidneys. However, we have shown that over a wide spectrum of whole-body retention measurements (18 to 70%) the 24-hr soft-tissue component, as a percentage of administered dose, remained relatively constant whereas skeletal tracer accumulation mirrored WBR (r = 0.98, p less than 0.001). The present study indicates that, despite a significant but essentially stable soft-tissue component, measurement of 24-hr WBR of HEDP accurately reflects skeletal metabolism.

Twenty-four-hour measurements of whole-body retention (WBR) of Tc-99m diphosphonate (a sensitive measure of skeletal metabolism) have been obtained in 250 healthy volunteer subjects. WBR values were found to fall from the age of 20 yr until 35 yr and then in men to rise linearly thereafter. Women showed a similar pattern initially but there was a marked rise in WBR corresponding to the menopausal years. Our results lend support to the belief that skeletal metabolism increases with age. It is suggested that some imbalance must always exist between resorption and formation in bone, with net loss of bone mineral, and increasing levels of skeletal metabolism will exaggerate this imbalance and accelerate the rate of bone loss.

Changes in osteoblast function, assessed by serial bone scans and serum alkaline phosphatase bone isoenzyme (ALP-Bl) and osteocalcin, have been studied in 53 patients receiving systemic therapy for bone metastases from advanced breast cancer. In 12/16 patients with healing of lytic disease on x-ray a paradoxical deterioration in the bone scan appearances after 3 mo treatment was seen. This was characterized by increased activity in baseline lesions and the appearance of new foci of tracer uptake; changes which are indistinguishable from progressive disease. After 6 mo successful treatment the bone scan improved with reduced tracer uptake and no new lesions since the 3-mo scan. New lesions appearing after 6 mo indicated progressive disease. These changes are attributed to a flare in osteoblast activity induced by successful systemic therapy and confirmed by a transient rise in osteocalcin and ALP-Bl. After 1 mo of treatment 15/16 responders showed a rise in both parameters compared with only 5/23 nonresponders (p = less than 0.001). The flare response is the rule rather than the exception after successful systemic therapy for bone metastases. The appearance of new lesions or increasing activity in known lesions during the first 3 mo is as likely to herald radiological response as disease progression.

The limited role of bone scanning in the diagnosis of metabolic bone disease might be considerably improved by accurate quantification of skeletal uptake of the radiopharmaceutical. Using a standard shadow-shield whole-body monitor, we have measured whole-body retention (WBR) of Tc-99m HEDP up to 24 hr in 11 patients with renal osteodystrophy (mean WBR 88.6% at 24 hr); in ten patients with Paget's disease (mean 56.9%); in seven patients with osteomalacia (mean 40.7%); in five patients with primary hyperparathyroidism (mean 50.7%); in four patients with osteoporosis (mean 21.2%); and in 12 normals (mean 19.2%). The osteoporotic group could not be differentiated from the normal group, but the other groups were significantly different from the normal group at 24 hr (p less than 0.002), and each individual rest for the 24-hr WBR of Tc-99m HEDP in these groups lay outside our normal range. This test may, therefore, provide a sensitive means of detecting conditions with increased bone turnover. We obtained measurements of plasma activity of Tc-99m HEDP in these patients up to 24 hr, and 4-hr bone to soft-tissue ratios from bonescan images, but little additional information resulted.