Technetium-99m Hydroxymethylene Diphosphonate Research Articles

Abstract 233: A Network Meta-analysis Comparing The Performance Of Magnetic Resonance Imaging, Positron Emission Tomography And Bone Scintigraphy Techniques In Detecting Cardiac Amyloidosis

Aims: Diagnosing cardiac amyloidosis with non-invasive imaging studies can be challenging. We aims to systematically review the published literature and compare the performance of magnetic resonance (CMR), positron emission tomography (PET) and bone scintigraphy (BS) for diagnosis of cardiac amyloidosis. Methods: Medical electronic databases were searched for studies evaluating the diagnostic performance of CMR, PET or BS in diagnosing cardiac amyloidosis where histopathological examination of endomyocardial biopsy tissue or extra-cardiac organs were used as reference standards. We evaluated; CMR: extracellular volume (ECV), late gadolinium enhancement (LGE), T1 mapping; PET: F18-Amyloid, F18-Sodium Fluoride (NaF), and C11-PIB; BS: Technetium-99m (Tc) hydroxymethylene diphosphonate (Tc-HMDP), Tc-3,3-diphosphono-1,2-propanodicarboxylicacid (Tc-DPD), Tc- pyrophosphate (Tc-PYP). Methodological quality was assessed using a Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). To summarize sensitivity, specificity, and superiority, we used an arm-based hierarchical model which expresses the logit transformed sensitivity and specificity as the sum of fixed effects for test, correlated study-effects to model the inherent correlation between sensitivity and specificity and a random error associated with various tests evaluated in each study. Results: Of the 2871 studies identified, 39 studies met the inclusion criteria. Sensitivity and specificity and Superiority of the various imaging modalities in diagnosing cardiac amyloidosis were calculated (Figure). Study quality assessed by QUADAS-2 was generally good with negligible evidence of bias. Conclusion: Various non-invasive imaging modalities have been studied for diagnosing cardiac amyloidosis with varying sensitivity and specificity. Comparative studies may be warranted to improve non-invasive diagnostic algorithms of suspected cardiac amyloidosis.

Assessment of a software for semi-automatically calculating the bone scan index on bone scintigraphy scans

AimsThe incidence of bone metastases exceeds 85% in patients who die from prostate cancer. Bone scintigraphy is the most widely used method for the early detection of bone metastases in prostate cancer. We developed a software program that semi-automatically calculated the bone scan index (BSI) on technetium-99m hydroxymethylene diphosphonate bone scintigraphy scans with a computer-aided diagnosis system (CAD) and examined whether the BSI calculated using this software could replace the extent of disease (EOD) score. MethodsThe subjects were 175 patients who were diagnosed with prostate cancer at our hospital and underwent bone scintigraphy. We analyzed receiver operating characteristic curves to determine the BSI cutoff value between EOD groups. The cutoff value was determined based on the maximum value of the sum of the sensitivity and specificity. ResultsBSI cutoff values of 0.20, 1.56, and 4.56 were used to distinguish between EOD 0 and 1–4 (sensitivity [87.2%] and specificity [100.0%]), between EOD 0- and 2–4 (sensitivity [85.2%] and specificity [92.0%]), and between EOD 0–2 and 3–4 (sensitivity [88.4%] and specificity [99.2%]), respectively. ConclusionOur results suggest that this software can calculate BSI, and the software may play a role in predicting prognosis and selecting an appropriate treatment strategy. If a sufficient number of other nuclear medicine tests are performed, creating a similar CAD system is possible.

Bone single-photon emission computed tomography-CT peak standardized uptake value for chronic osteomyelitis, osteoradionecrosis and medication-related osteonecrosis of the jaw.

Recently, standardized uptake value (SUV) has been applied for the evaluation of SPECT-CT. This study was performed to investigate the bone SPECT-CT peak SUV for chronic osteomyelitis, osteoradionecrosis and medication-related osteonecrosis of the jaw (MRONJ). Sixty-five patients with jaw lesions (12 chronic osteomyelitis, 12 osteoradionecrosis and 41 MRONJ) underwent SPECT-CT after injection of technetium-99m hydroxymethylene diphosphonate. The peak SUV was compared for the chronic osteomyelitis with osteoradionecrosis and MRONJ using GI-BONE software. Statistical analyses for the peak SUV were performed by one-way repeated measures analysis of variance with Tukey's HSD test. A P-value lower than 0.05 was considered as statistically significant. Peak SUV for chronic osteomyelitis (15.6±4.4) was significantly higher than those for osteoradionecrosis (6.7±2.1, P=0.000) and MRONJ (10.7±6.1, P=0.019). The SPECT-CT peak SUV using GI-BONE software can be useful for the evaluation of jaw lesions, such as chronic osteomyelitis, osteoradionecrosis and MRONJ.

Tumoricidal effect and pain relief after concurrent therapy by strontium-89 chloride and zoledronic acid for bone metastases.

The purpose of this study was to investigate the palliative and tumoricidal effects of concurrent therapy of strontium-89 chloride (89SrCl2) and zoledronic acid (ZA) for painful bone metastases. Fifty-one patients with painful bone metastases prostate cancer (n=17), lung cancer (n=13), breast cancer (n=12), other cancers (n=9) were treated. Bone metastases was confirmed in all patients by technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) bone scintigraphy. The numeric rating scale (NRS) and performance status (PS) were used to assess the degree of pain and patients' physical condition. The extent of bone metastases was assessed with imaging modalities including CT, MRI and/or 99mTc bone scintigraphy before treatment and 2 or 3 months after. The pain relief response of 89SrCl2 with ZA for bone metastases was 94% (48/51) from 1 to 3 months after treatment. The tumoricidal effect of concurrent therapy by 89SrCl2 with ZA for painful bone metastases was 8/22 as shown by imaging modalities and the rate of non-progressive disease (non-PD) was 19/22. Pain due to bone metastases assessed with the NRS was significantly improved (P<0.001) in many types of primary cancer, including prostate, breast and lung cancers. Concurrent therapy of 89SrCl2 with ZA may offer not only pain relief, but also a tumoricidal effect for painful bone metastases.

Maximum standardised uptake value of quantitative bone SPECT/CT in patients with medial compartment osteoarthritis of the knee

To evaluate the correlation between the maximum standardised uptake value (SUVmax) from bone single-photon-emission computed tomography/computed tomography (SPECT/CT) and other imaging parameters for medial compartment osteoarthritis (OA) of the knee. Patients (n=26; male:female=2:24; age, 55.3±5.8 years) underwent quantitative knee SPECT/CT using technetium-99m (Tc-99m) hydroxymethylene diphosphonate (HDP) before surgical operation for medial OA of the knee. SUVmax was calculated using dedicated quantitative software. Visual grades of tracer uptake on bone SPECT/CT and Kellgren-Lawrence (KL) OA scores on plain radiographs were assessed using a five-point scale. Magnetic resonance imaging (MRI) scores (n=22) and patient symptom scores were also assessed. The operated knees (n=34) had a greater SUVmax than the non-operated knees (n=18) in the medial compartment (14.1±6.1 versus 5.3±4.4, p<0.0001). In the medial compartment, the SUVmax was significantly correlated with SPECT/CT visual grades (rho=0.794, p<0.0001), KL scores (rho=0.703, p<0.0001), and MRI scores (rho=0.714-0.808, p≤0.0002); however, SUVmax and other imaging parameters were not correlated with patient symptom scores (p>0.05). The SUVmax of quantitative bone SPECT/CT was highly correlated with traditional imaging parameters for medial compartment OA severity of the knee. Quantitative bone SPECT/CT is a promising imaging technique for the objective assessment of knee OA.

Diagnostic utility of a computer-aided diagnosis system for whole-body bone scintigraphy to detect bone metastasis in breast cancer patients

To compare the diagnostic ability of planar images (PI) and images obtained by a computer-aided diagnosis (CAD) system (Viewer for Standardized Bone Scintigraphies; VSBONE) of whole-body bone scintigraphy for detecting bone metastases in breast cancer patients. 81 women (median: 56years; range: 32-79) with a history of breast cancer were included in this study. They underwent whole-body bone scintigraphy after intravenous injection of 740MBq technetium-99m hydroxymethylene diphosphonate. A total of 1066 bones (162 regions of the skull, 657 regions of the spine and pelvis, 223 regions of the sternum and rib, 18 regions of the upper extremities, and 6 regions of the lower extremities) were analyzed. The PI alone, VSBONE images alone, and both PI and VSBONE images (PI+VSBONE) were interpreted independently by two radiologists to diagnose bone metastases, which were then confirmed by magnetic resonance imaging. The sensitivity and specificity for each modality were analyzed using Fisher's exact and McNemar tests. Inter-reviewer agreement was evaluated using a kappa statistic. Bone metastases were confirmed in 43 patients with 442 positive lesions. The average sensitivity of PI, VSBONE images, and PI+VSBONE images was 40.8, 50.2, and 61.8%, respectively. The average specificity was 97.8, 97.5, and 97.6%, respectively. The kappa scores were 0.62 for PI, 0.69 for VSBONE, and 0.77 for PI+VSBONE. VSBONE was superior to PI in regard to sensitivity for detecting bone metastases in breast cancer patients. However, an improved CAD system is required to decrease the number of false-negative results.

Scintigraphic assessments of the reparative process in osteonecrosis of the femoral head using SPECT/CT with 99mTc hydroxymethylene diphosphonate.

The aim of the study was to assess the degree and location of the reparative process in early osteonecrosis of the femoral head on the basis of single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m hydroxymethylene diphosphonate. This study was approved by the institutional review board. We retrospectively evaluated SPECT/CT scans of 23 consecutive hips. On the basis of the classification system used, 12 hips were classified as stage 1 (no radiographic abnormality), six hips as stage 2 (demarcating sclerosis without femoral head collapse), and five hips as stage 3A (<3 mm femoral head collapse). In each femoral head, the area with the maximum uptake count was defined as the region of maximum uptake. The degree of maximum uptake was assessed by the count ratio, which was defined as the maximum count within the femoral head divided by the mean uptake count of the cross-sectional region of the ipsilateral femur at the level of the distal end of the lesser trochanter. In stage 1, the maximum uptake count tended to occur in the anterior region of the femoral head. Meanwhile, in both stage 2 and stage 3A, the maximum uptake count was more likely to be observed in the lateral region. The mean count ratio of stage 2 was significantly higher than that of stage 1. We speculate that osteoblastic activity in the precollapsed stage may gradually increase around the necrotic lesion, with a tendency to advance toward the lateral region of the femoral head.

Diffuse Myocardial Uptake of (99m)Tc-HDP in Multiple Myeloma.

Soft tissue uptake is a rare finding in bone scintigraphy, with an incidence of 2%. Although the mechanism has not yet been fully clarified, several causes have been reported for this unusual uptake pattern. This paper presents a case of diffuse myocardial accumulation of technetium-99m hydroxymethylene diphosphonate ((99m)Tc-HDP) without either solid/visceral organ or soft tissue with multiple myeloma (MM) in skeletal scintigraphy. A 93-year-old man with hypertension and chronic heart failure for 14years underwent bone scanning due to a 2-month history of back pain within a 1-year period of MM. Three hours later, (99m)Tc-HDP late static images showed diffuse myocardial radiotracer accumulation and there were no other sites of abnormal soft tissue or visceral uptake. Myocardial accumulation had disappeared on 24-h delayed static images. This accumulation was thought to be related with AL-type amyloidosis associated with MM.

Absent skeletal uptake of 99mTc-hydroxymethylene diphosphonate in the presence of AL-type amyloidosis associated with multiple myeloma

A 66-year-old woman with congestive heart failure suspected to have multiple myeloma underwent bone scintigraphy. The bone scintigraphy using technetium-99m hydroxymethylene-diphosphonate showed the following interesting findings: absent skeletal uptake; increased gastrointestinal, myocardial, and soft tissue uptake; migration of radionuclide to bilateral pleural effusions. Histopathological examination revealed that the patient suffered from AL-type amyloidosis associated with multiple myeloma. Extraosseous uptake is often observed on bone scintigraphy in amyloidosis patients, but in many cases skeletal uptake is preserved. The simultaneous presentation of these findings is rare.

IMAGING DIAGNOSIS—ENOSTOSIS‐LIKE LESION IN THE FEMUR OF A HORSE

An enostosis-like lesion was diagnosed in the left femur of a Swedish Warmblood horse that had a left hindlimb lameness of 3 weeks duration. With scintigraphy using technetium 99m-hydroxymethylene diphosphonate (99mTc-HDP) a marked regional focal increase in radioactivity was identified in the medullary cavity of the left femur. Radiographically there was a corresponding focal increase in bone opacity in the middiaphysis of the left femur. Histopathologically, a 5cm area of bone matrix was present in the diaphysis of the left femur and confirmed as an enostosis-like lesion. Enostosis-like lesions should be considered as a source of pain in horses with difficult to localize, moderate to severe chronic lameness.

Increased Bone Alkaline Phosphatase and Isolated Subcortical Bone Uptake of Technetium-99m Hydroxymethylene Diphosphonate in the Lower Extremities in a Patient with Graves' Disease: A Distinctly Unusual Variant of Graves' Acropachy

Thyroid acropachy is an extreme manifestation of autoimmune thyroid disease characterized by soft tissue swelling and periosteal bone changes, usually occurring in the fingers, toes, and lower extremities. Here, a patient with a distinctly unusual variant of thyroid acropachy is presented. The patient was a 48-year-old woman with Graves' disease and mild ophthalmopathy, who was euthyroid after treatment with Methimazole. Because of a persistently elevated serum alkaline phosphatase (ALP) with elevated bone fraction, a bone scan was performed. This showed increased uptake in the subcortical areas of the lower extremity bones. On questioning, she admitted to mild pain in her lower extremities. She had no other features of thyroid acropachy. Secondary causes of increased ALP, such as cancer, liver disease, and vitamin D deficiency, were excluded by appropriate tests. Therefore, and in view of the patient's underlying Graves' disease, a diagnosis of thyroid acropachy was made. Periosteal reaction in the long bones of the lower extremities is unusual in thyroid acropachy, and when it occurs, it is more likely to be associated with overt pain or prominent extrathyroidal manifestations of Graves' disease. This patient very likely had a variant of thyroid acropachy. This variant may be underreported because of its generally asymptomatic nature.

Use of the Navigator Probe after Radiotracer Injection to Identify Nonpalpable Rib Lesions Requiring Surgical Resection

: Patients with nonpalpable rib lesions (NPRL) requiring biopsy present a challenging problem for the thoracic surgeon. Ideally, a small incision directly over the NPRL should be performed to minimize morbidity, particularly if the lesion is benign. The Navigator probe is routinely used after lymphoscintigraphy by surgical oncologists to isolate sentinel lymph nodes requiring removal, but can also be used to guide resection of nonpalpable focal rib lesions demonstrating increased technetium-99m hydroxymethylene diphosphonate (Tc-99m HDP) uptake. This report describes our initial experience with this technique. : Over a 5-month period, 3 patients with focal NPRL underwent rib resection. All patients had solitary lesions demonstrated on recently performed Tc-99m HDP bone scanning. Prior cancers were reported in 2 patients, and pain in 2 patients. Before surgery, all patients underwent intravenous injection of 20 to 25 mCi Tc-99m HDP at least 2 hours before the Navigator probe-guided procedure. : The Navigator probe identified all 3 lesions, allowing a single 4 cm or smaller incision in all cases. Histology included metastatic breast cancer (1), pathologic fracture secondary to metastatic palatal cancer (1), and eosinophilic granuloma (1). No patient required further resection. : Intraoperative localization of NPRL that are positive on Tc-99m HDP bone scanning using the Navigator probe is feasible and was 100% successful in our initial experience. This technique allows a minimally invasive approach, which is beneficial for those patients who do not require further resection.

Evaluation of delayed-image bone scintigraphy to assess bone formation after distraction osteogenesis in dogs

To quantitatively assess distraction-induced bone formation in a crural lengthening model in dogs by use of delayed-image bone scintigraphy. 12 mature Labrador Retrievers. Dogs were randomly allocated to 1 of 3 groups. A circular external skeletal fixation system was mounted on the right crus of each dog. Osteotomy of the distal portion of the tibia and fibula was performed in groups 1 and 2 and was followed by a lengthening procedure of 10 mm in the first group only. The third group served as sham-operated controls. Delayed-image bone scintigraphy with technetium-99m hydroxy methylene diphosphonate was performed 2, 4, and 6 weeks after surgery. Delayed-image-to-region-of-interest, delayed-image-to-crural, and delayed-image-to-femoral scintigraphic activity ratios were calculated. New bone formation was quantified by use of densitometric image analysis, and values for the scintigraphic ratios were compared. In the distraction and osteotomy groups, delayed-image-to-region-of-interest and delayed-image-to-crural ratios increased significantly. Although densitometric image analysis revealed increased bone formation after distraction, the region-of-interest ratios and crural ratios were similar in both groups. All dogs had increased delayed-image-to-femoral ratios. Delayed-image bone scintigraphy ratios were not effective at differentiating between the amounts of distraction-induced bone and osteotomy-induced bone. Metabolic bone activity in the adjacent femur was increased as a consequence of circular external skeletal fixator placement. Delayed-image bone scintigraphy was not adequately sensitive to quantitatively monitor bone formation but may be useful as an early predictor of bone healing.

Quantification of diphosphonate uptake based on conventional bone scanning.

Up to now there has been no routinely used and easy-to-perform method for the quantification of bone uptake. Therefore, we have evaluated the clinical practicability of a new and simple method for the measurement of bone uptake based upon conventional three-phase bone scanning. In 13 patients with normal bone scans, whole-body scintigrams were obtained at 3 min and 1, 2, 3, 4, 5, 6 and 24 h after injection of 600 MBq technetium-99m hydroxymethylene diphosphonate (HMDP). Using a conventional region of interest technique, fitted time-activity curves of soft tissue and urinary excretion were established, and bone uptake was calculated from these data as the total whole-body activity minus both soft tissue activity and urinary excretion. Subsequently, the new method was tested in routine patient management: 32 healthy patients and five patients with different types of metabolic bone disease were investigated, measurements being performed only at 3 min and 3-4 h p. i. during conventional three-phase bone scanning. In the multi-imaged patient subset, soft tissue activity decreased exponentially, reaching a plateau after 6 h with a residual activity of about 14% of initial total whole-body activity. Bone uptake reached quite a stable plateau of about 27% as early as 3 h p.i., with no significant changes up to 24 h. Healthy patients of the two-scan group showed no differences in bone uptake (mean uptake values were 24.1% in women and 26.9% in men), whereas in patients with metabolic bone disease bone uptake was significantly higher, with a mean of 48% (P <0.05). Thus, the results of this method are in good agreement with the findings of standard 24-h whole-body retention measurements. The new method, however, is easy to perform, allows assessment of pure bone uptake instead of whole-body retention, and permits calculation of bone uptake by only two measurements during routine three-phase bone scanning.

A comparative study of scatter correction methods for scintigraphic images

Phantom studies have demonstrated that factor analysis of medical image sequences using target apex-seeking (FAMIS-TAS) applied to spectral scintigraphic image sequences is an efficient adaptive scatter correction method. We assessed the improvement in quality of clinical images using FAMIS-TAS as compared with two other scatter correction techniques: conventional 20% photopeak window (PW) and scatter window subtraction (SWS). Thirty normal technetium-99m hydroxymethylene diphosphonate bone scans were processed. Bone to soft tissue contrasts and signal-to-noise and contrast-to-noise ratios were measured. The overall image quality was evaluated using an observer testing questionnaire submitted to four physicians. Quantitative parameters showed that FAMIS-TAS images displayed the best bone to soft tissue contrasts and contrast-to-noise ratios, but the lowest signal-to-noise ratios. PW images presented the lowest contrasts and contrast-to-noise ratios, and the highest signal-to-noise ratios. SWS gave intermediate results. According to the observer testing results, PW images showed the lowest bone to soft tissue contrasts and the highest signal-to-noise ratios. FAMIS-TAS images showed the lowest signal-to-noise ratios. The images processed by the three methods displayed the same anatomical information.

Usefulness of technetium-99m hydroxymethylene diphosphonate scans in localizing bone metastases of differentiated thyroid carcinoma

Iodine-131 is uniquely able to demonstrate iodine uptake of differentiated thyroid carcinoma (DTC), but precise localization may be difficult, especially in the thorax, due to the quality of image resolution with 131I and the lack of anatomical landmarks. When bone metastases do not show radioiodine uptake bone scintigraphy can be used to detect them. We studied two groups of patients. In group 1, 15 patients with known bone metastases of DTC were treated with 3.7 GBq 131I. After 4 or 5 days, technetium-99m hydroxymethylene diphosphonate (HMDP; 740 MBq) was injected and a whole-body scan with simultaneous acquisition of 131I and 99mTc-HMDP images was carried out using a large field of view gamma camera fitted with a high-energy collimator. Technetium uptake was abnormal in 47 of 63 localizations, being increased in 29 foci, decreased in 7 and heterogeneous in 11. The superimposition of 131I and 99mTc-HMDP scans permitted an accurate localization in 80% of spine metastases and in 46% of osseous thoracic localizations, even in the presence of lung metastases. In group 2, 9 patients, who had bone pain, neurological signs or elevated serum thyroglobulin, had DTC bone metastases without iodine uptake. They received a diagnostic dose of 99mTc-HMDP 3h prior to scintigraphy with a large field of view gamma camera fitted with a low-energy collimator. Technetium uptake was abnormal in 37 of 38 localizations, being increased in 34 foci and decreased in 3. One false-negative was found in a skull metastasis. In both groups of patients, 99mTc-HMDP scans were useful.(ABSTRACT TRUNCATED AT 250 WORDS)

Factor analysis as a means of determining response to chemotherapy in patients with osteogenic sarcoma.

The prognosis of localized osteogenic sarcoma (OS) has improved considerably since the introduction of neoadjuvant chemotherapy. However, there is a subset of patients who do not show full benefit from neoadjuvant chemotherapy because of chemoresistance. The early identification of poor responders to chemotherapy during neoadjuvant therapy remains difficult. In order to evaluate the role of bone scintigraphy we report our experience of dynamic technetium-99m hydroxymethylene diphosphonate bone scintigraphy in 19 cases of paediatric osteogenic sarcomas. Before the beginning of chemotherapy, a dynamic scan was recorded during 30 min followed by static images at 3 h. The procedure was repeated halfway through the course of chemotherapy (6th week). Histological grading of the response to chemotherapy was carried out in the 12th week, showing nine good responses and ten poor responses. Factor analysis of dynamic structures (FADS) applied to dynamic scans allowed us to identify three factors termed vascular, "soft tissue" and osseous factors. The effect of chemotherapy on each factor was evaluated. Using FADS we were able to detect all the poor histological responders with the combination of vascular and osseous factors. Six out of nine good histological responders were also classified as scintigraphic responders. FADS applied to dynamic bone scans allowed us to identify at an early stage all the poor histological responders to neoadjuvant chemotherapy. This method may have clinical relevance for the therapeutic strategy in patients with OS.

Technetium-99m hydroxymethylene diphosphonate scanning of acute injuries to the lateral ligaments of the ankle.

Technetium-99m hydroxymethylene diphosphonate scans were performed on 29 consecutive patients with acute ankle ligament injuries. Scanning reliably differentiated a severe from a minor injury. Severe injuries gave a diffuse uptake on the scan and the minor injuries a more localized increase in uptake.