Technetium Tc 99m plasmin in the diagnosis of inflammatory disease

The localization characteristics of technetium Tc 99m plasmin were studied in experimental animals to investigate the use of^99mTc-plasmin for imaging inflammatory processes. At various times after abscess induction using turpentine in rats, the in vivo distribution properties of^99mTc-plasmin, gallium citrate Ga 67,¹²⁵I-fibrinogen, and^99mTc-human serum albumin (HSA) were studied by gamma-camera imaging. The in vivo binding of each radiopharmaceutical was also tested in rat and human plasma clots. Region-of-interest analyses of gamma-camera images showed relatively poor^99mTc-plasmin localization at sites of abscess formation. The ratio of abscess-to-control activity of this radiopharmaceutical did not exceed that of⁶⁷Ga,¹²⁵I-fibrinogen, or^99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed^99mTc-phasmin and¹²⁵I-fibrinogen to have the best localization characteristics.     

Studies of 99mTc-acylplasmins as agents for thrombus detection

It has been proposed that acylation at the active site of plasmin is able to prevent its reaction with alpha 2-antiplasmin without affecting the fibrin affinity of the enzyme. To investigate the possibility that 99mTc-labelled acylplasmins are improved thrombus-detecting agents, six acylating agents were synthesised and their reaction with plasmin and the labelling of the products with 99mTc studies. Uptake of 99mTc-acylplasmins in an in vitro thrombus model was complicated by precipitation processes, which may in part account for the rapid blood clearance in rabbits and high liver uptake in mice injected with the compounds. Quantitative measurements using an in vivo rabbit thrombus model demonstrated that guanidinobenzoyl-plasmin exhibited nearly a threefold increase in thrombus uptake compared with non-acylated 99mTc-plasmin. The observed uptake is less than that obtained with 125I-fibrinogen at clinically useful time intervals post-injection but represents a significant advantage over the use of 99mTc-plasmin.     

Tc-99m-labeled C5a and C5a des Arg74 for infection imaging

The complement anaphylatoxin C5a and its natural metabolite C5a des Arg(74) (C5adR) are involved in several stages of the inflammatory process. Both act on a common receptor expressed on different cell types, including neutrophils and monocytes. The receptor binding affinity of C5a is in the nanomolar range and exceeds that of C5adR by 1-2 orders of magnitude. The biologic potency of C5a is considerably higher than that of C5adR. Here we tested both proteins labeled with (99m)Tc for imaging of infection. METHODS: The proteins were labeled with (99m)Tc via the hydrazinonicotinamide (HYNIC) chelator. The preparations were tested for imaging of infection in a rabbit model of intramuscular infection. Biodistribution of the radiolabel was determined by gamma-camera imaging and by counting dissected tissues at 5 h p.i. RESULTS: C5a and C5adR showed in vivo abscess uptakes of 0.12 and 0.025%ID/g, abscess/muscle ratios of 76 and 14, abscess/blood ratios of 9.1 and 2.6, and ROI derived target-to-background ratios of 5.9 and 2.1, respectively at 5 h p.i. CONCLUSION: For infection imaging (99m)Tc-labeled C5a showed excellent in vivo characteristics. However, C5a is a very bioactive protein, impeding its clinical use as an infection imaging agent. The naturally occurring partial agonist C5adR has less biological effect but showed suboptimal imaging characteristics. The present study showed that for adequate localization of a receptor binding ligand affinities for the receptor in the nanomolar range are required.     

Tumor model studies of 131I-tetracycline and other compounds.

Iodine-131-tetracycline (131I-TET) was prepared by allowing tetracycline hydrochloride to react with radioiodide in acidic methanol (labeling efficiency greater than 85%). This preparation was found to be stable at--4 degrees C for at least 72 hr. Some minimal in vivo breakdown did occur. The 131I-TET, 67Ga, and several 99mTc compounds were studied in a rat hepatoma model. The incorporation of the radiopharmaceuticals into the tumor occurred rapidly, with peak levels at 0.5 and 24 hr after injection for 131I-TET and 67Ga, respectively. The clearnace of the radiopharmaceutical from nonviable tumor was slower than for viable tumor, and by 72 hr after injection the greatest concentration of radioactivity appeared in the nonviable fraction. All normal tissues showed faster clearance than did tumor tissue, regardless of viability. Decreasing the quantity of 131I-TET injected increased the percent of uptake in the nonviable tumor tissue but had no effect on the viable tumor uptake. Of the 99mTc compounds studied, the phosphates developed the highest tumor-to-background ratios. Unfortunately these ratios were not as high as those achieved for 67Ga or 131I-TET.     

Nuclear medicine and infection detection: the relative effectiveness of imaging with 111In-oxine-, 99mTc-HMPAO-, and 99mTc-stannous fluoride colloid-labeled leukocytes and with 67Ga-citrate

With a current annual mortality rate of around 35% worldwide, infection remains a significant concern, and the diagnosis and localization of infectious foci is an important health issue. As an established infection-imaging modality, nuclear medicine plays a vital health-care role in the diagnosis and subsequent effective treatment of this condition. Despite the development of several newer radiopharmaceuticals, (67)Ga and leukocyte imaging procedures have maintained their established place for infection. Several techniques in nuclear medicine significantly aid infection diagnosis, including imaging with (111)In-oxine-, (99m)Tc-hexamethylpropyleneamine oxime-, and (99m)Tc-stannous fluoride colloid-labeled leukocytes and with (67)Ga-citrate. Each radiopharmaceutical has specific advantages and disadvantages that make it suitable to diagnose different infectious processes (e.g., soft-tissue sepsis, inflammatory bowel disease, osteomyelitis, occult fever, fever of unknown origin, and infections commonly found in immunocompromised patients). After finishing this article, the reader should be able to identify the properties of an ideal radiopharmaceutical for infection imaging, list a range of available infection-imaging radiopharmaceuticals, compare the relative results of a range of radiopharmaceuticals used internationally to detect infection in the body, understand several common infectious processes that can be diagnosed using nuclear medicine techniques, and select an appropriate radiopharmaceutical to image a range of infectious processes.     

67Ga-labeled human fibrinogen: A new promising thrombus imaging agent

Gallium-67 labeled fibrinogen was prepared as a new deep-vein thrombus imaging agent, using deferoxamine (DF) as a bifunctional chelating agent. Excellent physicochemical and biological properties of ⁶⁷Ga-DF-fibrinogen were obtained. The isotopic clottability was 85.3%. High stability in vivo as well as in vitro was observed. Studies carried out in rabbits with induced thrombi in the femoral vein showed thrombus to blood radioactivity ratio of 11.7, comparable to the value estimated with conventional ¹³¹I-fibrinogen 24 h after injection. Remarkable visualization of these thrombi with a scintillation camera provided good evidence for the selective mechanism of this new radiopharmaceutical.     

Dual radionuclide subtraction imaging of the spleen

Dual radionuclide subtraction imaging of the spleen using 67Ga citrate and 99mTc is useful in further delineating lesions that are identified on either a routine radiogallium survey or on a conventional sulfur colloid liver-spleen image. Better anatomic localization of left subphrenic abscesses may be obtained. Differentiation of tumors and abscesses from less serious lesions such as cysts, infarcts, and hematomas is possible. We have found this technique to be generally applicable to any organ that can be selectively imaged using a technetium radiopharmaceutical, including the liver, bones, and kidneys. In addition, we are currently evaluating thallium-pertechnetate subtraction imaging in the evaluation of parathyroid adenomata.     

Thyroid imaging in a typical case of acute suppurative thyroiditis with abscess formation due to infection from a persistent thyroglossal duct

The clinical evaluation of thyroid imaging with^99mTc,²⁰¹T1, and⁶⁷Ga in the uncommon, but potentially serious, disorder of acute suppurative thyroiditis (AST) with abscess formation due to infection from a persistent thyroglossal duct is reported. The^99mTc image showed functioning areas of the diseased thyroid gland and the²⁰¹Tl image demonstrated abscess formation in the thyroid gland of this patient. In addition, marked⁶⁷Ga accumulation was demonstrated in a wide area covering not only the area of the thyroid gland involved, but also associated circumferential inflammatory lesions in a patient with AST. The net thyroid uptake of⁶⁷Ga at 72 hours was calculated to be 13.8% of the injected dose.     

The role of 67Ga in the early detection of spinal epidural abscesses

In this study, we evaluated the role of 67Ga whole-body and single photon emission tomographic (SPET) imaging in the early diagnosis and lesion localization of spinal epidural abscess before confirmation by gadolinium-enhanced magnetic resonance imaging (MRI). Six patients with fever of unknown origin had a 67Ga whole-body scan, four of whom also underwent SPET imaging. For further confirmation of a spinal epidural abscess, gadolinium-enhanced MRI was performed in all patients. All patients had increased 67Ga uptake in a spinal or paraspinal area on the whole-body scan. They were later confirmed to have a spinal epidural abscess after gadolinium-enhanced MRI. Of these six patients, five underwent surgical drainage plus parenterally administered antibiotics, and had complete or partial recovery. One died before operation due to sepsis. In conclusion, we suggest performing a 67Ga whole-body survey as early as possible in patients with fever of unknown origin, fever and back pain and/or the spinal syndrome, before MRI is performed. If a spinal epidural abscess is strongly suspected, SPET is needed for further confirmation of spinal versus non-spinal and contiguous versus non-contiguous lesion(s). If MRI is unavailable, then 67Ga scintigraphy is a satisfactory method for investigating spinal epidural abscesses.     

In vivo kinetics and thrombus accumulation of 67Ga-labeled urokinase

Highly purified high and low molecular weight urokinase (H-UK and L-UK) were labeled with 67Ga using deferoxamine (DF) as a bifunctional chelating agent. The labeling efficiency was 91.7% for the H-UK, and 90.4% for the L-UK, respectively. The 67Ga labeled UK (67Ga-DF-UK) fully retained the enzymatic activity of the parent UK. Studies on the in vivo behavior of the 67Ga labeled UK in rabbits showed a very rapid blood clearance with half-life of 4 min (67Ga-DF-L-UK) to 8 min (67Ga-DF-H-UK). Studies carried out in rabbits with induced thrombi in the femoral vein showed thrombus-to-blood 67Ga-DF-UK activity ratios, 2h after injection, of 2.00-3.08 for the H-UK, and 0.84-1.65 for the L-UK, respectively, with thrombi aged 4 to 3 days. A dose effect of the 67Ga-DF-H-UK on its thrombus accumulation was observed. Gel chromatographic analysis of plasma samples withdrawn from those animals injected with this radiopharmaceutical revealed a reduction of the 67Ga-DF-UK effectiveness due to complexation with protein inhibitors. This led to formation of high molecular weight complexes which was reflected in the very fast blood clearance. Its implication in thrombus accumulation is discussed. In conclusion, usefulness of DF for labeling UK with 67Ga or 68Ga with no alteration of UK enzymatic properties was demonstrated. The use of 67Ga-DF-UK as a diagnostic or therapeutic radiopharmaceutical is promising.     

Detection of osteomyelitis at fracture nonunion sites: comparison of two scintigraphic methods

Forty-nine patients with 50 fracture nonunions 4-48 months after injury underwent technetium-99m methylene diphosphonate (99mTc-MDP) scintigraphy on day 1, combined 99mTc-MDP and indium-111 leukocyte (111In-WBC) scintigraphy on day 2, and gallium-67 (67Ga) scintigraphy on day 3. The results were compared to evaluate the relative abilities of these scintigraphic techniques to detect osteomyelitis. Nine patients had clinical evidence of infection at the time of imaging, and 40 patients (41 fractures) did not. Open-biopsy cultures were performed at all fracture sites and were positive at 21 (42%) of the 50 sites. Combined 99mTc-MDP/111In-WBC images were interpreted with the use of two criteria. A positive study by the first criterion required 111In-WBC localization in the region of the nonunion fracture. A positive study by the second criterion required 111In-WBC localization in bone at the fracture site. The first criterion yielded a sensitivity of 84%, specificity of 72%, and accuracy of 74%; the specificity improved to 97% with an accuracy of 88% when the second criterion was used. Ten (25%) of the 40 patients thought not to have osteomyelitis by clinical criteria at the time of imaging had true-positive 99mTc-MDP/111In-WBC studies by biopsy culture results. Gallium-67 studies were interpreted as nondiagnostic if localization of radioisotope at fracture sites was equal to that with 99mTc-MDP, positive if 67Ga localization was greater than that of 99mTc-MDP, and negative if it was less than that of 99mTc-MDP. Twenty-one 67Ga studies were interpreted as nondiagnostic; 11 (52%) of the 21 had culture-positive fracture sites. The accuracy of 67Ga/99mTc-MDP imaging was 39%. Combined 99mTc-MDP/111In-WBC imaging is useful in the detection of osteomyelitis at fracture nonunion sites and improves the specificity of 111In-WBC imaging by differentiating inflammation/infection in adjacent soft tissue from osteomyelitis at the fracture site. Gallium-67 with 99mTc-MDP imaging is not sufficiently reliable in this clinical setting to be useful as an indicator for osteomyelitis.     

97Ru-transferrin uptake in tumor and abscess

The uptake of 97Ru-transferrin (Ru-TF) in tumor and abscess bearing animals was compared with 67Ga-citrate (Ga), 123I-transferrin (I-TF), and several other plasma proteins. Maximal concentration in tumor of Ru-TF in mice was three times higher than 67Ga-citrate (16.80 +/- 4.20 vs 5.08 +/- 0.58% D/g) although it occurred later (24 h compared with 67Ga which reached its maximum 2 h after injection). Whole body autoradiography (WBARG) with 103Ru-transferrin (103Ru-TF) in tumor and abscess bearing rats demonstrated details of the distribution within these lesions. Turpentine-induced abscesses in the rabbits could be visualized with the gamma camera as early as 30 min post-injection of Ru-TF. It seems, therefore, that Ru-TF can be used for tumor and abscess localization. The results indicate that Ru-TF may have some advantages over 67Ga-citrate because of the higher concentration in the lesions. 123I-transferrin reached a concentration in tumor similar to 67Ga (6.89 +/- 1.67 vs 5.08 +/- 0.58% D/g) but had a very low tumor to blood ratio (0.64). The three compounds investigated (Ru-TF, I-TF and ionic Ga, which binds instantaneously to TF in vivo) have a common ligand, transferrin. It appears, therefore, that tumor affinity is a property of the radionuclide-ligand complex rather than of the radionuclide itself.     

Bone tumor imaging by scintigraphy of the skeleton, marrow reticuloendothelial system, and the proliferative tissue.

Paralleled clinical studies of radioisotopic imaging or tumor metastases in the bone were undertaken with Tc99m pyrophosphate, Ga67 citrate, and Tc99m sulfur colloid. All three were capable of anticipating the bone roentgenograms. A critical analysis suggested that positive delineation with Ga67 citrate would sometimes be superior to the others. This deserves further investigation. Clinically the combined use of Tc99m pyrophosphate with Ga67 for the chest areas and extremties or with Tc99m colloid for the pelvic and abdominal areas would be more frutiful in early detection and exact localization of bone metastases.     

Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: comparison with gallium-67 citrate and technetium-99m-labeled albumin

The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with 125I or 111In was compared to that of [67Ga]citrate and [99mTc]albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, [111In]IgG showed greater accumulation at the lesion than [99mTc]HSA (p less than 0.01). Both [125I]IgG and [111In]IgG showed greater accumulation than [67Ga]citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of [67Ga]citrate or [99mTc]HSA (p less than 0.01). At all imaging times, [67Ga]citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, [111In]IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG.     

Comparison of radiolabeled bleomycins and gallium citrate in tumor-bearing mice.

Radioiodinated bleomycin is a chemically stable radiopharmaceutical that can be prepared with high specific activity using 123I. Its pharmacokinetics were compared with those of 99mTc,- 111In-, and 57Co-bleomycin, and 67Ga citrate in mice bearing a transplanted KHJJ tumor. The in vivo kinetics and stability of 123I- and 57Co-bleomycin were similar: both were acceptable, although not equivalent, tags for bleomycin and, along with 67Ga citrate, both had biologic properties suitable for tumor detection. Both 99mTc- and 111In-bleomycin dissociated rapidly in vivo and hence do not represent legitimate tags for bleomycin. However, 111In-bleomycin may have tumor-localizing properties related to its biochemical properties after the indium and chelate separate in vivo. Iodine-123 is superior to either 57Co or 55Co. Tumor-to-blood and tumor-to-liver ratios were higher for I-bleomycin than for 67Ga or Co-bleomycin. The nearly ideal nuclear properties of 123I should complement the biologic properties of bleomycin and lead to a useful tumor radiodiagnostic agent.     

Gallium-67 distribution in a man with a decrease in both transferrin and hepatic gallium-67 concentration.

A patient with reduced transferrin concentration had a 67Ga scintigram that showed uptake in a peritoneal abscess, pericarditis and pleural effusion but only faint liver uptake. Gallium-67 activity was measured in liver, lung, muscle and plasma samples obtained at autopsy. The percent injected dose/kg for liver and plasma samples was considerably lower than previously reported while that in muscle and lung tissues values were comparable to prior data. In this patient, sites on transferrin available to bind 67Ga were reduced from the normal 40 microM to 5.2 microM; this in turn increased the concentration of radiogallate from 1% to 7%. This elevated free activity increased 67Ga excretion and reduced the amount of 67Ga*transferrin species. These results and those of previous studies suggest that liver uptake is slower than abscess uptake and more sensitive to concentration of 67Ga*transferrin. Iron status is an important facet of the interpretation of 67Ga scintigrams.     

Colon carcinoma immunoscintigraphy by monoclonal anti-CEA antibody labeled with gallium-67-aminooxyacetyldeferroxamine.

Previous experimental results in nude mice showing that radiolabeling the monoclonal antibody anti-CEA 35 with 67Ga-aminooxyacetyldeferroxamine could give better tumor localization than radioiodination prompted us to initiate the present clinical study. The 67Ga-labeled antibody anti-CEA 35 (185 MBq, 0.7-1.7 mg) was injected preoperatively into 14 patients for colorectal carcinoma imaging. The same antibody labeled with 125I (3.7 MBq, 0.25 mg) was injected simultaneously to compare the 67Ga and 125I dose recoveries in surgical specimens. Twelve of 14 primary tumors gave a positive 67Ga scintigraph. The mean %ID/g recovered in all tumors 3-9 days after injection was significantly higher for 67Ga (0.019%) than for 125I (0.005%) (p < 0.001, paired t test). The tumor-to-normal tissue ratios were generally higher for 67Ga, with the exception of liver. We conclude that 67Ga-aminooxyacetyldeferroxamine improved immunoscintigraphy outside the liver, particularly in the pelvic region. We also show that deferroxamine infusion accelerates the excretion of 67Ga in eight patients and propose that this could lead to further improvement of immunoscintigraphy.     

The effect of molecular weight on nonspecific accumulation of (99m)T-labeled proteins in inflammatory foci

Although several proteins have been proposed and tested for scintigraphic detection of infection, the most optimal characteristics of a protein for this application have not yet been determined. Molecular weight (MW) of the protein, its charge, shape, carbohydrate content, characteristics of the radionuclide and receptor interactions are factors that could affect the in vivo behavior of the infection imaging agent. The effect of molecular weight on nonspecific accumulation of (99m)Tc-labeled proteins in inflammatory foci was studied in a rat model.Methods: Eleven proteins whose MWs ranged from 2.5 kDa up to 800 kDa were labeled with (99m)Tc using the hydrazinonicotinamide (HYNIC) chelator. Rats with S. aureus infection were injected i.v. with 15 MBq (99m)Tc-labeled protein. Gamma camera images were acquired and biodistribution of the radiolabel was determined ex vivo.Results: From biodistribution data no significant correlation was found between abscess uptake and molecular size of the (99m)Tc-labeled proteins that were studied. Fast blood clearance with predominant uptake in liver and spleen was found for the largest proteins (MW 669 kDa-800 kDA). For proteins of intermediate size (MW 66 kDa -206 kDa) we found relatively slow blood clearance with relatively moderate uptake in liver and spleen. For smaller proteins (MW 2.5 kDa -29 kDa) rapid blood clearance with predominant kidney uptake was observed. The abscess uptake of the (99m)Tc-labeled proteins (%ID/g, 24 h p.i.) was highest for serum proteins IgG and BSA. Abscess uptake correlated well with blood levels: r = 0.95 and 0.84 at 4 and 24 h respectively (P < 0.005). The abscess-to-muscle ratios varied from 2.1 to 17.8 at 24 h p.i. with highest values for alpha-2 macroglobulin (MW 725 kDa) and the intermediate sized proteins (MW 66-206 kDa). Gamma camera imaging showed localization of all radiotracers at the site of infection with abscess-to-background ratios (A/B) ranging from 1.4 to 7.0 (IgG) at 20 h p.i. The serum proteins IgG and BSA showed highest blood levels and best infection imaging characteristics.Conclusion: Not molecular weight but blood residence time is the principal factor that determines localization of a nonspecific tracer protein in infectious foci. The ideal nonspecific infection imaging agent is a protein with a long circulatory half-life. From the proteins tested here IgG and albumin showed the best characteristics for an infection imaging agent.     

In vitro and in vivo characterization of 67Ga(3+) complexes with cis,cis-1,3,5-triamino-cyclohexane-N,N',N"-triacetic acid derivatives

The aim of this study was to investigate the in vitro and in vivo performance of a 67Ga complex with cis,cis-1,3,5-triaminocyclohexane-N,N',N"-triacetic acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET imaging. The radiolabeling procedure, electrophoretic properties, lipophilicity, acid stability, human serum stability and biodistribution in mice of 67Ga(tachta) were investigated. The 67Ga(tachta) complex forms at 10(-3) M tachta concentration at 40 degrees C in 100% yield; it is neutral, non-lipophilic, 90% stable at pH = 4 and 5 and 100% stable at pH = 6, for at least 8 d. Serum stability experiments demonstrated that at 5 hr 67Ga(tachta) exists in serum as a free complex. At 24 hr, 30% of 67Ga(tachta) is reversibly bound to transferrin-albumin fraction of serum, and that this percentage remains unchanged for a period of 4 d. Biodistribution in mice showed that 67Ga(tachta) rapidly clears via the kidneys from the body with less than 10% of injected activity left in the body at 3 hours and only 6% remaining after 24 hr. The complex also cleared rapidly from all of the major organs, with bone showing some slightly increased (1.15% ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based upon these data, 67Ga(tachta) may be considered as a candidate for developing new Ga(III) radiopharmaceuticals for PET.     

The value of gallium-67 and thallium-201 whole-body and single-photon emission tomography images in dialysis-related beta 2-microglobulin amyloid

The aim of this study was to investigate the value of gallium-67 and thallium-201 whole-body and single-photon emission tomography (SPET) images in long-term dialysis patients in whom dialysis-related beta 2-microglobulin amyloid (beta 2-MA) was clinically suspected. Twenty-three patients who had received dialysis for at least 10 years were included in the study. A technetium-99m methylene diphosphonate (MDP) whole-body scan was performed in all of the patients. If there was any MDP accumulation in the articular and/or peri-articular region, 67Ga and 201Tl whole-body and SPET images were then acquired. If any 67Ga and/or 201Tl uptake was observed, a CT-guided biopsy was done. In those patients who had articular and/or peri-articular uptake of 99mTc MDP, 67Ga and/or 201Tl and who were pathologically proven to have beta 2-MA, 99mTc MDP, 67Ga and 201Tl whole-body scans and SPET were carried out again, both 3 months and 1 year after initiation of treatment. This served to evaluate the therapeutic effect and allowed comparison with the clinical findings. Of the 23 patients, eight had abnormal 99mTc MDP uptake. Among these eight, six had intense 99mTc MDP, 67Ga and 201Tl uptake in the articular and peri-articular regions before medication. Three months after the start of treatment, there were very marked decreases in uptake on both the 67Ga and 201Tl scans but less obvious changes in uptake of 99mTc-MDP. In comparison with the other clinical manifestations such as limitation in range of motion, the more the painful disability improved, the less was the uptake on both 67Ga and 201Tl scans. There were virtually no differences in uptake pattern between the three scans of each radiopharmaceutical obtained for each patient in both 3 months and 1 year after initial of treatment. It is concluded that 99mTc-MDP whole-body bone scan can both detect active and pre-existing inactive deposits of beta 2-MA. 67Ga and 201Tl scans are helpful to differentiate active from inactive deposits of beta 2-MA and to evaluate the therapeutic effect on these patients. SPET images are usually needed to distinguish articular and periarticular lesions from bone lesions.