Electrolytically labeled [99mTc]MDP: chromatographic pattern, stability and biodistribution in rats

The labeling of methylene diphosphonate with 99mTc is possible after reduction of pertechnetate by means of controlled potential electrolysis. This results in a [99mTc]MDP complex which differs slightly from 99mTc(Sn)-MDP in paper and gel chromatography. The scintigraphic images of both preparations are comparable in quality. Biodistribution in rats shows a higher bone uptake for the 99mTc(Sn)-MDP complex, whereas [99mTc]MDP shows a higher uptake in the gastric wall.     

The use of computed tomography to quantitate bone formation after distraction epiphysiolosis in the rabbit

A study of limb lengthening by distraction epiphysiolysis in the rabbit tibia is presented. For this purpose a special external distraction device was developed, which allowed 10 mm lengthening of the leg. Bone formation in the distraction zone was quantified by means of computed tomography. Cross-sectional scan planes at 1.5 mm separation revealed bone formation proceeding for several weeks after the end of the distraction period. A period of bone remodeling followed, resulting in the formation of a solid cortical structure, similar to the diaphysis, in the distraction zone.     

Bone metabolism in thalassemic children with multiple transfusions. Compartmental analysis of 99mTc-Sn-MDP kinetics

The kinetics of 99mTc(Sn) methylene diphosphonate [99mTc(Sn)MDP] were evaluated by means of compartmental analysis in 5 normal children and 17 thalassemic subjects. Blood and urine activity were analyzed with a computer program which generates intercompartmental rate constants by an iterative least-square method providing a best-fit to the input data. The amount of tracer in each compartment (corrected for decay) was determined as a function of time. The transfer rate of 99mTc(Sn)MDP from blood to extracellular fluid and lamellar bone (K1-3) was about 20% higher in thalassemic subjects than in normal children. The transfer rate of 99mTc(Sn)MDP from blood to woven bone (K1-4) was about 57% higher in thalassemic subjects. A faster rate of spread into woven bone appears to be the major cause of higher bone uptake of 99mTc(Sn)MDP in thalassemic subjects, which suggests that in these patients bone tissue reoccupies the space previously replaced by hyperplastic marrow. Moreover, the increased bone extraction rate revealed a correlation between anemia and bone metabolic activity.     

Skeletal localization of samarium-153 chelates: potential therapeutic bone agents

A series of stable complexes of 153Sm has been produced using multidentate acetate and phosphonate ligands. Biodistribution studies in unanesthetized rats showed varying degrees of bone and soft-tissue uptake for these complexes. Of the complexes studied, [153Sm] ethylenediaminetetramethylenephosphonate (EDTMP) showed the best combination of high bone uptake, low nonosseous uptake, and rapid blood clearance which warranted its further investigation in rabbits. Rabbit studies confirmed the [153Sm]EDTMP results obtained in rats. Blood clearance in rabbits was found to be more rapid than [99mTc] methylene diphosphonate (MDP). Scintigraphic images were virtually indistinguishable from [99mTc]MDP images. Lesion/normal bone ratios were determined from digitized images obtained using a drill hole model and found to be approximately 17:1. Based on these excellent biodistribution characteristics, [153Sm] EDTMP could be therapeutically useful in treating metastatic bone cancer.     

15例口腔颌面外科疾病患者的骨显像结果分析

目的 探讨骨显像对口腔颌面部病变的诊断和鉴别诊断的临床价值。方法 用＾９９Ｔｃ＾ｍ－亚甲基二膦酸（ＭＤＰ）对５例正常人，１５例患者（３例下颌骨造釉细胞瘤、５例口腔内鳞状细胞癌、２例下颌胚胎型横纹肌肉瘤、１例舌血管瘤、１例下颌骨肉瘤、１例下颌骨囊肿、１例腮腺慢性炎症和１例拔牙后患者）进行三相骨显像、断层显像和半定量分析。结果 ３例下颌骨造釉细胞瘤均表现为＾９９Ｔｃ＾ｍ－ＭＤＰ浓聚，５例口腔鳞癌和下颌     

Electrophoretic analysis of different technetium-99m (SnCl2) methylene diphosphonate complexes

Technetium-99m MDP was prepared from MDP kits from several different sources. The resulting [99mTc]MDP preparations were analyzed by electrophoresis. The results demonstrated the presence of at least four different 99mTc complexes in these preparations. Modified kit preparations were analyzed to show the effects of concentration and pH on formation of the impurities. The electrophoresis results were correlated with scintillation camera imaging studies in rabbits and suggest that hydrolysis of MDP to phosphate and methylphosphate results in formation of 99mTc complexes with poor biological behavior as bone scanning agents.     

Reversible pulmonary uptake and hypertrophic pulmonary osteoarthropathic distribution of technetium-99m methylene diphosphonate in a case of Pneumocystis carinii pneumonia

Diffuse pulmonary deposition of [99mTc]methylene diphosphonate (MDP) as well as abnormalities characteristic of hypertrophic pulmonary osteoarthropathy have been observed in a patient with Pneumocystis carinii pneumonia (PCP). The findings of the bone scan together with those in the corresponding scintigraphy, and roentgenograms of the chest and skeletal structures are presented. Parallel reversal of [67Ga]citrate and [99mTc]MDP pulmonary uptake with specific treatment for and clinical resolution of PCP implies a causal relationship.     

Correlations between uptake of technetium, calcium, phosphate, and mineralization in rat tibial bone repair

Technetium-99m-(99mTc) phosphates are extensively used for detection of bone formation and resorption. The present is a study of 99mTc incorporation during bone remodeling. Uptake of 99mTc-labeled phosphate was studied in an animal model of primary osteogenesis following tibial marrow injury and incorporation was correlated to that of calcium-47 (47Ca), phosphorus-32 (32P), and with matrix vesicle calcification. Isotope uptake on Day 6 in the whole bone was increased compared to controls. On this day, an increase in vesicular diameter and distance from the calcified front was previously observed. Technetium-99m-labeled phosphates were detected only in the organic phase. Phosphorus-32 and 47Ca were detected in both organic and inorganic phases. It is suggested that 99mTc serves as a specific marker to the anabolic phase of remodeling. Increased incorporation of 99mTc during bone healing indicates enhanced organic matrix formation and not calcification.     

Radionuclide bone imaging findings in recurrent calvarial infarction in sickle cell disease

A patient with sickle cell disease developed bi-parietal calvarial infarctions, and subsequently developed bi-frontal calvarial infarctions. The findings on [99mTc]MDP bone imaging showed decreased activity in the parietal and frontal regions during the phase of acute infarction and increased activity in the parietal region during the later healing phase. Thus the findings on radionuclide bone imaging in cortical infarcts will depend upon the stage of the condition.     

Hematogenous pyogenic vertebral osteomyelitis: diagnostic value of radionuclide bone imaging

Hematogenous pyogenic vertebral osteomyelitis (HPVO) continues to be a diagnostic problem for clinicians due to nonspecific presentation of the disease (1,2). We reviewed our experience of the last 10 years to determine the diagnostic usefulness of radionuclide bone studies in this disease. We found 15 patients whose primary diagnosis was HPVO. Of the 15 patients, 12 had [99mTc]MDP bone scans which were all positive. Five of the 12 patients had positive [67Ga]citrate scans and one patient with chronic active HPVO had negative 67Ga and [111In]WBC bone images. At the same time, three patients' spine x-rays and one patient's CT scan of the vertebra were normal. Additionally, in three patients spine x-rays were interpreted as consistent with degenerative joint disease that contributed to the delay of the diagnosis. We conclude that when HPVO is suspected an abnormal [99mTc]MDP bone image increases the probability of the disease, even if the x-rays and CT scans of the spine are normal. An abnormal 67Ga image following an abnormal 99mTc bone image increases the specificity of the diagnosis. Normal [99mTc]MDP and [67Ga]citrate bone images of the vertebra virtually exclude the diagnosis of HPVO.     

Technetium-99m APD compared with technetium-99m MDP as a bone scanning agent

We have investigated the possibilities of technetium-99m-(-3-aminohydroxypropylidene)-1-1-bisphosphon ate ([99mTc]APD) as a bone scanning agent in 14 normal subjects and 28 patients. Similar studies in the same normal subjects and patients were carried out with 99mTc-methylene-bisphosphonate ([99mTc]MDP). The compounds were labeled with 99mTc by means of an electrolytical method; the free pertechnetate content was always under 1%. The [99mTc]APD T1/2 of the third component of the disappearance plasma curve in six normal subjects was 152 +/- 46 min (mean +/- s.d.), while the 24-hr whole-body retention (WBR) was 17.6% +/- 4.6. The [99mTc]MDP value of the 24-hr WBR was 28.6% +/- 3.9 (p less than 0.001). The bone/soft-tissue ratio (B/ST) was investigated in eight control subjects on the eleventh thoracic and the fourth lumbar vertebrae. The B/ST ratios were similar for both APD and MDP studies. In 28 patients with suspected bone metastasis or primary bone disease, bone scintigraphy was carried out; both compounds showed similar findings and the same number of positive results. In five of these patients, the lesion/normal bone ratio was determined with values of 4.6 +/- 2.0 in APD studies and 4.8 +/- 2.3 with MDP. APD was also used in 126 patients; no adverse reactions were observed. The APD dose used i.v. for bone scanning was 200-fold less than those employed by mouth per day, for the treatment of bone disease for long periods. In our experience, APD appears to be an adequate agent for bone scintigraphy.     

Gaucher's disease type 1: assessment of bone involvement by CT and scintigraphy

The effectiveness of CT and technetium-99m sulfur colloid (99mTc SC) bone-marrow scans in determining the extent and severity of skeletal involvement in 23 patients with type 1 Gaucher's disease was compared with the effectiveness of conventional radiographic techniques and technetium-99m methylene diphosphonate (99mTc MDP) bone scintigrams. Density measurements obtained by CT proved sensitive in differentiating normal marrow (-50 to -120 H). Scintigrams with the sulfur colloid nuclide demonstrated three distinct patterns of uptake: peripheral expansion of normal marrow (profile B), greater marrow expansion with patchy areas lacking uptake (profile C), and greater loss of uptake with retention of the nuclide in other reticuloendothelial organs and circulation (profile D). CT scans provided greater sensitivity in resolving the extent of marrow involvement in affected areas, while the 99mTc SC scintigrams were more effective in overall assessment of the severity of bone-marrow involvement. Both conventional radiographic techniques and 99mTc MDP bone scans were useful primarily as screening procedures or for evaluating specific involved areas. 99mTc MDP scans were useful in evaluating regional defects (i.e., ischemic necrosis) in certain cases, but no consistent patterns were observed. CT and 99mTc SC scans are useful for determining the extent and severity of Gaucher's disease involvement of bone marrow.     

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.     

Acute effects of radiation therapy on indium-111-labeled leukocyte uptake in bone marrow

We recently performed [99mTc]MDP bone and 111In-labeled leukocyte scintigraphy on a patient receiving radiation therapy to the lower cervical and upper thoracic spine. While the bone images revealed only minimally increased activity in the radiation port, leukocyte images revealed diffuse, intensely increased uptake in this same region. Radiation therapy should be included in the differential diagnosis of increased bone marrow activity on 111In leukocyte images.     

Comparative uptake of 67Ga and 99mTc MDP in rabbits with a benign noninfected bone lesion (fracture)

Mid-shaft fractures of the radius and ulna were produced in 3 to 4 kg New Zealand white rabbits and quantitative uptake of 99mTc MDP and 67Ga determined at 11, 18, 25, 32, 51, and 78 days following fracture. Two hundred microCi of 67Ga was administered 24 hours prior to sacrifice and 1.5 mCi 99mTc MDP 2 hours prior to sacrifice. Specific activity ratios (SARs) were determined between fracture and control sides for bone, muscle and skin. SARs for bone were surprisingly similar for 99mTc MDP and 67Ga, reaching peak values of 6.07 +/- 0.64 (99mTc 18 days); 6.58 +/- 0.90 (67Ga 32 days), subsequently decreasing to minimum values at 78 days postfracture (99mTc MDP 2.25 +/- 0.14; 67Ga 2.18 +/- 0.08). There was no statistically significant difference in SAR for 99mTc MDP vs. 67Ga in bone at any time after fracture. Whole sections of limb were resected on selected animals and activity ratios determined for these sections as a function of the contribution of activity from the various tissues in the volume of interest. Total activity ratios of 67Ga were lower than bone SARs as a result of the contribution of activity from muscle and skin. Thus the apparent lower activity ratios noted on 67Ga images compared with 99mTc MDP images in this fracture model were not due to differences in bone SARs but rather due to the higher soft tissue background activity contribution in the 67Ga images.     

Iodine-131 MIBG scintigraphy of the extremities in metastatic pheochromocytoma and neuroblastoma

Iodine-131 MIBG scintigraphy may be used to determine the presence or absence of metastases to the appendicular skeleton in malignant pheochromocytoma and neuroblastoma. Normal bones show no uptake of [131I]MIBG and the joints are seen as photon-deficient areas surrounded by background muscle activity. Discrete concentrations of radioactivity in bone are often seen in patients with malignant pheochromocytoma and neuroblastoma. Bone marrow involvement in neuroblastoma may be indicated by diffuse uptake of [131I]MIBG or focal accumulation at the metaphyses. Uncommonly, bone involvement may not be displayed by the [131I]MIBG images. Since conventional bone scanning agents may also fail to detect these tumors, skeletal scintigraphy with both [131I]MIBG and [99mTc]MDP is necessary to reliably stage malignant pheochromocytoma and neuroblastoma.     

Quantitative bone scintigraphy using SPECT

A quantitative single photon emission computed tomography (SPECT) technique for measuring radiopharmaceutical uptake in humans has been applied to bone scintigraphy. The method was validated by comparing SPECT measured percent of injected [99mTc]MDP in 16 normal skulls with well counter measurements of samples of the same bones obtained at surgery. A very good correlation (r = 0.96) was found. A very good interobserver correlation (r = 0.99) and agreement were also obtained when using quantitative bone scintigraphy (QBS). Control SPECT studies of uptake in the right and left iliac bones and the right and left sacroiliac regions in each patient showed no significant differences between the contralateral sides. Studies done in seven subjects at 2 and 4 hr after the same injection and in nine subjects 4 to 8 mo later in the same subjects showed a very good agreement and no significant differences between the two measurements were found. QBS is suggested as an accurate and reproducible index for assessment of the mass of remodeling bone. Preliminary results showed differences in QBS of normal subjects at different ages. A group of 68 young patients aged 18-26 yr showed a significant higher QBS (p less than 0.001) when compared to an older group of 62 patients aged 50-85 yr. There was, however, a wide range of uptake values for the same bone in the same group, suggesting that the method should best be used for following individual patients over time.     

Preclinical evaluation of technetium 99m-labeled P1827DS for infection imaging and comparison with technetium 99m IL-8

BACKGROUND: The technetium 99 m (99mTc)-radiolabeled, leukocyte-avid peptide-glycoseaminoglycan complex, [99mTc]P1827DS, has been synthesized as an improved infection/inflammation imaging agent to [99mTc]P483H (LeukoTect, Diatide). In a phase I/II clinical trail, [99mTc]P483H images were equivalent to those obtained with 111In ex vivo labeled leukocytes. However, there was physiologic accumulation of radioactivity in the body that could hamper interpretation of the images. In this study, the potential of [99mTc]P1827DS for infection imaging was assessed in comparison with [99mTc]P483H and the well-described imaging agent [99mTc] hydrazinonicotinamide (HYNIC)-interleukin 8 (IL-8). METHODS: The binding of [99mTc]P1827DS to human blood cell was studied in vitro. A rabbit Escherichia coli infection model was used to perform the biodistribution and imaging studies with [99mTc]P1827DS, [99mTc]P483H and [99mTc]HYNIC-IL-8. RESULTS: [99mTc]P1827DS binds to leukocytes but not to erythrocytes. The leukocyte binding was not saturable up to an investigated concentration of 10 microM. The accumulation of [99mTc]P1827/DS at the infection site strongly depends on the P1827/DS ratio and was optimal at a molar ratio of 10:1. [99mTc]P1827DS shows improved biodistribution over [99mTc]P483H with similar uptake at the infection site. Abscess uptake of [99mTc]HYNIC-IL-8 was approximately three times higher than that of [99mTc]P1827DS. [99mTc]HYNIC-IL-8 showed high accumulation in the kidneys, whereas [99mTc]P1827DS showed high lung uptake and slightly higher accumulation in the liver and spleen. CONCLUSION: [99mTc]P1827DS is a potential new inflammation imaging agent, which clearly visualized the abscess in the rabbit E. coli infection model and showed improved biodistribution compared to [99mTc]P483H. However, the infection uptake and biodistribution of [99mTc]P1827DS is not superior to that of [99mTc]HYNIC-IL-8 in this animal model.     

Pentavalent [99mTc]DMSA, [131I]MIBG, and [99mTc]MDP--an evaluation of three imaging techniques in patients with medullary carcinoma of the thyroid

Nine patients with histologically proven medullary carcinoma of the thyroid (MCT) were imaged using pentavalent [99mTc]dimercaptosuccinic acid [(V)DMSA], [131I] metaiodobenzylguanidine (MIBG) and [99mTc]methylene diphosphonate (MDP). Technetium-99m (V)DMSA demonstrated most of the tumor sites in eight patients with proven metastases, with an overall sensitivity of 95% in lesion detection. Iodine-131 MIBG showed definite uptake in some of the tumor sites in three of the nine patients imaged, with equivocal uptake seen in a further one patient, with sensitivity of only 11% for lesion detection. Technetium-99m MDP demonstrated bony metastases only, in four of the patients imaged yielding a sensitivity of 61%. Technetium-99m (V)DMSA has been demonstrated in this study to be a useful imaging agent in patients with MCT, showing uptake in significantly more lesions and with better imaging qualities than [131I]MIBG, and with the ability to detect soft tissue as well as bony metastases.     

Biokinetics of bone tracers by means of deconvolution analysis--comparison of 99mTc MDP, 99mTc DPD and 99mTc EHDP

Transfer functions of 99mTc methylene diphosphonate (MDP), 99mTc 2,3-dicarboxypropane-1,1-diphosphonate (DPD) and 99mTc ethane-1-hydroxy-1,1-diphosphonate (EHDP) into bone and extravascular fluid of soft tissues were determined in 5 dogs by deconvolution analysis of the time-course of plasma, soft tissue and bone radioactivity. The transfer rates 5 min after injection--indicating the rapid exchange of the tracer between plasma and the extravascular fluid--decrease in the order MDP greater than EHDP greater than DPD (P less than 0.05). The transfer rates into bone--determined from transfer rates between 30 and 60 min--decreased in a different order, i.e. MDP greater than DPD greater than EHDP (P less than 0.05). The fractional bone uptake of diphosphonates estimated from the ratio of early to late transfer rates was slightly greater for DPD than for MDP and EHDP respectively. The difference between DPD and MDP was not significant (P greater than 0.05). The average bone and soft tissue concentrations of DPD 60 min after injection were greater than that of MDP and EHDP due to different plasma concentrations (DPD greater than EHDP greater than MDP), whereas the bone-to-soft tissue ratios decreased in the sequence MDP greater than DPD greater than EHDP (P less than 0.05).--Our results reveal different biokinetics of MDP, DPD and EHDP explaining variations in osseous and soft tissue uptake suggesting that deconvolution analysis could play an important role in bone scan interpretation.