Cardiac scintigraphy with 99mTc-diphosphonates in cardiac amyloidosis. / Gammagrafía cardíaca con 99mTc-difosfonatos en la amiloidosis cardíaca.

Transthyretin cardiac amyloidosis (ATTR) has traditionally been considered a rare, difficult-to-diagnose and untreatable disease. However, its prevalence is known to be greater than what was previously thought, non-invasive diagnostic methods are available, and that effective treatments are emerging. In this context, cardiac scintigraphy (CS) with 99mTc-labelled diphosphonates has aroused a noticeable surge in interest by demonstrating high sensitivity and specificity for the reliable, non-invasive diagnosis of ATTR. By way of a guide, this article aims to identify the critical components in the performance of CS that are useful in everyday clinical practice and, thus, help specialists use optimal radiopharmaceuticals, obtain the most appropriate images, interpret the results thereof, and acquaint themselves with those clinical scenarios in which it is convenient to perform CS.

Pattern of myocardial 99mTc-HMDP uptake and impact on myocardial function in patients with transthyretin cardiac amyloidosis.

AIMS: The purpose of the study was to describe the pattern of 99mTc-labeled phosphate agents myocardial uptake by scintigraphy and explore its impact on left ventricular (LV) functions in transthyretin cardiac amyloidosis (TTR-CA). METHODS: Fifty patients with TTR-CA underwent 99mTc- hydroxymethylene-diphosphonate (99mTc-HMDP) scintigraphy and echocardiography with measure of LV thickness, longitudinal strain (LS), systolic and diastolic functions. Cardiac retention by scintigraphy was assessed by visual scoring and the heart/whole body (H/WB) ratio was calculated by dividing counts in the heart by counts in late whole-body images. RESULTS: The mean population age was 79 ± 10 years. Mean H/WB ratio was 12 ± 7. Myocardial 99mTc-HMDP uptake on segments 5, 6, 7, 8, 11, 12, 13, 14, 16, and 17 was correlated with H/WB ratio. Mean LVEF and global LS were 51 ± 10% and - 10 ± 3%, respectively. H/WB ratio was correlated with global LS (R = 0.408, P = .003), Ea (R = - 0.566, P < .001) and mean left ventricular wall thickness (R = 0.476, P < .001) but not with LVEF (R = - 0.109, P = .453). Segmental myocardial uptake was slightly correlated with segmental LS (R = 0.152, P < .001). H/WB ratio was not correlated with NT-proBNP levels (R = 0.219, P = .148) neither E/Ea ratio (R = 0.204, P = .184). CONCLUSION: These findings show the relationship between bone tracer myocardial uptake and LV functions in patients with TTR cardiac amyloidosis.

SPECT Imaging of Muscle Injury with [99mTc]MDP in a Mouse Model of Muscular Dystrophy.

PURPOSE: Tc-99m methylene diphosphonate ([99mTc]MDP) is an in vivo bone imaging agent that also accumulates in injured skeletal muscle cells. The objective of this study was to investigate if [99mTc]MDP could be used to detect muscle injury in the mdx mouse model of Duchenne muscular dystrophy (DMD). PROCEDURES: Static whole-body single-photon emission computed tomography/computed tomography (CT) scans were acquired at 2 h post-injection of [99mTc]MDP in two cohorts of animals at different sites: one cohort of mice at 6, 15, and 19 weeks of age, and a separate cohort at 16 weeks. The second cohort was also imaged with high-resolution CT at 8 weeks. RESULTS: mdx mice had higher [99mTc]MDP uptake and significantly higher [99mTc]MDP concentrations in muscle than controls. CONCLUSIONS: Higher uptake of [99mTc]MDP in muscle of mdx mice agrees with histological reports of muscle calcification in mdx mice, and suggests the potential translational use of [99mTc]MDP imaging for tracking DMD progression and therapeutic response.

Accurate characterization of 99mTc-MDP uptake in extraosseous neoplasm mimicking bone metastasis on whole-body bone scan: contribution of SPECT/CT.

BACKGROUND: 99mTc-labelled methylene diphosphonate (99mTc-MDP) uptake can occasionally be identified in extraosseous neoplasms on whole-body scans (WBSs) and may be misinterpreted as bone metastasis. The purpose of our study was to investigate the frequency of 99mTc-MDP uptake in extraosseous neoplasms and to assess the additional value of SPECT/CT for the localization and characterization of this unusual uptake. METHODS: Data from 7308 patients (SPECT/CT was performed in 2147 patients) with known cancer who underwent WBSs for metastatic work-up between May 2015 and July 2018 were retrospectively reviewed. The locations, numbers, and intensities of extraosseous 99mTc-MDP uptake were evaluated by WBS, and the intratumoural calcification was evaluated by SPECT/CT. The diagnostic accuracy of SPECT/CT in locating 99mTc-MDP uptake in extraosseous neoplasms was compared to that of WBS. RESULTS: A total of 41 patients showed 99mTc-MDP uptake in extraosseous neoplasms. Of these patients, 23 patients had uncertain lesions by WBS, and further SPECT/CT was performed. The incidence of 99mTc-MDP uptake in extraosseous neoplasms was observed to be 0.6% by WBS and 1.1% (by) SPECT/CT. During imaging analysis, WBS had an accuracy of only 35% (14/40), whereas SPECT/CT correctly located and diagnosed all 40 lesion sites in the 23 patients. Twenty-three lesion sites (57.5%, 23/40) showed moderate or high intensity of extraosseous 99mTc-MDP uptake. Of the 23 patients, 17 patients (73.9%, 18/23) with 31 lesion sites (77.5%, 31/40) presented with intratumoural calcification. CONCLUSIONS: 99mTc-MDP uptake in extraosseous neoplasms can be observed as 0.6% on WBS and is usually localized to the breast, liver, and lung. Nuclear physicians should be familiar with such extraosseous uptake when interpreting WBSs. SPECT/CT offers better accuracy than WBS alone for locating the majority of lesions present with intratumoural calcification.

Freehand-SPECT with 99mTc-HDP as tool to guide percutaneous biopsy of skeletal lesions detected on bone scintigraphy. / Freehand-SPECT con 99mTc-HDP como herramienta para guiar la biopsia percutánea de lesiones esqueléticas detectadas en la gammagrafía ósea.

PURPOSE: To assess the feasibility of using freehand Single Photon Emission Computed Tomography (freehandSPECT) for the identification of technetium-99m-hydroxydiphosphonate (99mTc-HDP) positive bone lesions and to evaluate the possibility of using these imaging data-sets for augmented- and virtual-reality based navigation approaches. MATERIAL AND METHODS: In 20 consecutive patients referred for scintigraphy with 99mTc-HDP, 21 three-dimensional freehandSPECT-images were generated using a handheld gamma camera. Concordance of the two different data sets was ranked. Furthermore, feasibility of segmenting the hotspot of tracer accumulation for navigation purposes was assessed. RESULTS: In 86% of the cases freehandSPECT images showed good concordance with the corresponding part of the scintigraphic images. In lesions with a signal to background ratio (SBR) >1.36, freehandSPECT provided an automatically segmented reference point for navigation purposes. In 14% of the cases (average SBR 1.82, range 1.0-3.4) freehandSPECT images showed intermediate concordance due to difficult anatomical area or negative bone scintigraphy and could not be used as navigation targets. CONCLUSION: In this pilot study, in 86% of the cases freehandSPECT demonstrated good concordance with traditional scintigraphy. A lesion with a SBR of 1.36 or more was suitable for navigation. These high-quality freehandSPECT images supported the future exploration navigation strategies, e.g. guided needle biopsies.

Comparison of Bone Uptake in Bone Scan and Ga-68 PSMA PET/CT Images in Patients with Prostate Cancer.

OBJECTIVE: The aim of this study was to compare images from Tc-99m MDP bone scan (BS) and Ga-68 PSMA PET/CT of patients with prostate cancer in terms of bone metastases. METHODS: Overall, 34 patients exhibited a mean age of 66 ± 9.5 (50-88) years, mean PSA of 51 ± 159ng/ml (0-912), and mean Gleason score of 8 (6-9). BS and Ga-68 PSMA PET/CT were applied to 34 patients within 30 days, and the results were evaluated, retrospectively. In both tests, radiopharmaceutical uptake in bones were compared. RESULTS: In 7 patients (20.5%), uptake was not significant on BS and Ga-68 PSMA PET / CT images, which is related to metastasis. In 14 (41%) patients, bone metastases were observed in both examinations. However, more metastatic lesions were observed in the Ga-68 PSMA PET/CT of 3 patients and in the bone scintigraphy of 2 patients. PSMA expression was not observed on Ga-68 PSMA PET / CT in 13 (38%) patients with increased activity in bone scintigraphy. Two (6%) of these patients were thought to be metastatic, 2 (6%) were suspicious for metastasis, and 9 (26%) had no metastasis. When a lesion-based evaluation was performed, a total of 480 activities were evaluated: increased activity uptake was found in 305 BS, and 427 PSMA expression activity was detected. Furthermore, 435 of these activities were evaluated as metastatic. CONCLUSION: Ga-68 PSMA PET/CT provides an additional contribution to the BS evaluation of activity areas because of the presence of PSMA expression and anatomical lesions. In 6% of the patients, activity on BS and metastatic appearance in CT images were observed and the presence of lesions in the absence of PSMA was determined. This suggests that bone metastases without PSMA expression may also be present.

99mTc-MDP as an imaging tool to evaluate the in vivo biodistribution of solid lipid nanoparticles.

The aim of this study was to establish the in vivo uptake and tissue distribution of 99mTc-MDP-encapsulated Solid Lipid Nanoparticles (SLNs) post administration. Radioactive 99mTc-MDP encapsulated into SLNs was administered to rats to trace their biodistribution through imaging and ex vivo studies. As expected IV injected 99mTc-MDP exhibited predominant visual bone uptake and a high localisation of particles in the kidneys (3.87%ID/g) followed by bone (2.66%ID/g). IV administered 99mTc-MDP encapsulated by SLN showed similar uptake than 99mTc-MDP. Orally administrated 99mTc-MDP showed no uptake in any organs except the GI-tract while orally administered 99mTc-MDP-SLN showed distinct transfer of 99mTc-MDP from the GI tract with measurable levels in the kidneys and bone.

A retrospective study of SPECT/CT scans using SUV measurement of the normal pelvis with Tc-99m methylene diphosphonate.

OBJECTIVE: To perform quantitative measurement based on the standardized uptake value (SUV) of Tc-99m methylene diphosphonate (MDP) in the normal pelvis using a single-photon emission tomography (SPECT)/computed tomography (CT) scanner. MATERIAL AND METHODS: This retrospective study was performed on 31 patients with cancer undergoing bone SPECT/CT scans with 99mTc-MDP. SUVmax and SUVmean of the normal pelvis were calculated based on the body weight. SUVmax and SUVmean of the bilateral anterior superior iliac spine, posterior superior iliac spine, facies auricularis ossis ilii, ischial tuberosity, and sacrum were also calculated. Furthermore, the correlation of SUVmax and SUVmean of all parts of pelvis with weight, height, and CT was assessed. RESULTS: The data for 31 patients (20 women and 11 men; mean age 58.97±9.12 years; age range 37-87 years) were collected. SUVmax and SUVmean changed from 1.65±0.40 to 3.8±1.0 and from 1.15±0.25 to 2.07±0.58, respectively. The coefficient of variation of SUVmax and SUVmean ranged from 0.22 to 0.31. SUVmax and SUVmean had no statistically significant difference between men and women. SUVmax and SUVmean also showed no significant correlation with weight and height. However, part of SUVmax and SUVmean showed a significant correlation with CT. In addition, SUVmax and SUVmean of the bilateral ischial tuberosity showed a significant correlation with CT values. CONCLUSIONS: Determination of the SUV value of the normal pelvis with 99m Tc-MDP SPECT/CT is feasible and highly reproducible. SUVs of the normal pelvis showed a relatively large variability. As a quantitative imaging biomarker, SUVs might require standardization with adequate reference data for the participant to minimize variability.

Meniscal pathologies on MRI correlate with increased bone tracer uptake in SPECT/CT.

OBJECTIVES: To assess the relationship of subchondral bone tracer uptake (BTU) on SPECT/CT and meniscal pathologies on MRI in patients with painful knees. METHODS: Twenty-five patients who had MRI and SPECT/CT within 3 months without knee surgery or grade ≥3 cartilage lesions were prospectively included. Maximum values of each subchondral femorotibial area were quantified and a ratio was calculated in relation to a femoral shaft reference region, which represented the BTU background activity. Meniscal lesions were graded (intact/degeneration/tear) and meniscal extrusion (no/yes) was assessed using MRI by two musculoskeletal radiologists blinded to the SPECT/CT findings. One-tailed Spearman correlations served for statistics (p < 0.05). RESULTS: Knees with meniscal degeneration or tear showed a significantly higher BTU in the medial femorotibial compartment (p = 0.045) when compared to intact menisci. Meniscal degeneration was associated with an increased BTU in the lateral femorotibial compartment; however, this was not statistically significant (p = 0.143). Patients with an extruded meniscus showed significantly higher BTU compared to a non-extruded meniscus (p < 0.020). CONCLUSIONS: Medial femorotibial BTU in SPECT/CT was associated with meniscal pathologies. Highest BTU was found in patients with meniscal tears. SPECT/CT appears to be a useful imaging modality to identify patients with overloading or early osteoarthritis. KEY POINTS: • Meniscal degeneration and tears correlate significantly with increased BTU using SPECT/CT. • Medial meniscus extrusion is associated with an increased BTU in SPECT/CT. • SPECT/CT allows detection of overloading and early osteoarthritis.

Long-lasting Intense Bone Tracer Activity at the Sites of Collagen Injection.

Collagen injection has been used as dermal filler in plastic and cosmetic surgery. A technetium Tc methylene diphosphonate bone scintigraphy was performed in a 47-year-old woman as part of the breast cancer evaluation. The images showed intense methylene diphosphonate activity on both sides of the frontal head, where she received collagen injection 1 year prior. The activity was visualized again in all 3 follow-up bone scans over the subsequent 3 years.

Apical sparing pattern of left ventricular myocardial 99mTc-HMDP uptake in patients with transthyretin cardiac amyloidosis.

BACKGROUND: A decreased longitudinal strain in basal segments with a base-to-apex gradient has been described in patients with cardiac amyloidosis (CA). OBJECTIVES: Aim was to investigate the left ventricular (LV) regional distribution of early-phase 99mTc-Hydroxymethylene diphosphonate (99mTc-HMDP) uptake in patients with transthyretin-related cardiac amyloidosis (TTR-CA). METHODS: All patients underwent a whole-body planar 99mTc-HMDP scintigraphy acquired at 10-min post-injection (early-phase) followed by a thorax SPECT/CT. The segmental uptake (expressed as % of maximal myocardial HMDP uptake) was investigated on the AHA 17-segment model and 3-segment model (basal, mid-cavity, apical). RESULTS: Sixty-one TTR-CA patients were included of whom 29 were wild-type (wt-TTR-CA) and 32 had hereditary TTR-CA (m-TTR-CA). Early myocardial 99mTc-HMDP uptake occurred in all TTR-CA. In all patients, segmental analysis of the LV myocardial distribution of 99mTc-HMDP uptake showed an increased median uptake (interquartile range) in basal/mid-cavity segments compared to the lowest median uptake of apical segments (respectively, 79% [72%-86%] vs. 72% [64%-81%]; P < 10-6). This pattern was similar in wt-TTR-CA group (78% [70%-84%] vs. 70% [61%-81%]; P < 10-6), in m-TTR-CA group (80% [74%-86%] vs. 73 [66%-82%]; P < 10-7) and remained constant independently of the TTR mutation subtype with P ranging 10-5 to 0.03. CONCLUSIONS: Early-phase myocardial scintigraphy identified regional distribution of 99mTc-HMDP uptake characterized by a base-to-apex gradient, corroborating echocardiographic, and cardiac magnetic resonance findings. This apical sparing pattern was similar across TTR-CA and TTR mutation subtypes.

Early-phase myocardial uptake intensity of 99mTc-HMDP vs 99mTc-DPD in patients with hereditary transthyretin-related cardiac amyloidosis.

BACKGROUND: This study sought to compare the intensity of early-phase myocardial uptake of two phosphonate-based radiotracers, 99mTc-hydroxymethylene diphosphonate (HMDP) and 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), in patients with hereditary transthyretin-related cardiac amyloidosis (TTR-CA). METHODS: Six patients with biopsy-proven diagnosis of TTR-CA and characteristic amyloid fibril composition underwent early-phase 99mTc-HMDP myocardial scintigraphy as part of their routine workup; they were later assessed by 99mTc-DPD scintigraphy after having signed informed written consent. Heart-to-mediastinum-ratio was measured at both time points as well as regional distribution on 17-segment analysis. RESULTS: All patients had an H/M ratio >1.28 on both imaging. 99mTc-DPD uptake was slightly higher than 99mTc-HMDP uptake in 3 patients, but no statistical difference was found (P = 0.13). Regional distribution of the two radiotracers was well correlated on bull's eyes analysis, with only slight underestimation of 99mTc-DPD uptake in the anterior/apical segments, compared with 99mTc-HMDP. CONCLUSION: 99mTc-HMDP and 99mTc-DPD show comparable myocardial uptake intensity on early-phase scintigraphy and can be used alternatively for the diagnosis of TTR-CA.

Review of Extraskeletal Activity on Tc-99m Methylene Diphosphonate Bone Scintigraphy and Value of Cross-Sectional and SPECT-CT Imaging Correlation.

Recognizing the different mechanisms and imaging appearance of extraskeletal Tc-99m methylene diphosphonate uptake enhances the diagnostic value of bone scan interpretation. In this article, we present a pictorial review of the different mechanisms of extraskeletal Tc-99m methylene diphosphonate uptake on bone scintigraphy including neoplastic, inflammatory, ischemic, traumatic, excretory, and iatrogenic. We also illustrate through case examples the added value of correlation with cross-sectional and single photon emission computed tomography and computed tomography imaging in localizing and characterizing challenging cases of extraskeletal uptake.

Metabolic activity in bone metastases of breast and prostate cancer were similar as studied by 18F-FDG PET/CT. The role of 99mTc-MDP.

OBJECTIVE: The aim of this study was to compare the metabolic activity of metastatic foci from breast and prostate cancer patients as scanned by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and by technetium-99m methyl diphosphonate (99mTc-MDP) bone scan (BS). SUBJECTS AND METHODS: Forty one patients were studied, divided into 2 groups based on histologically confirmed diagnosis: a) Breast cancer group, 23 women, mean age: 61±12 years, range: 37-79 years and, b) Prostate cancer group, 18 men, mean age 68±8 years, range: 52-82 years. Another group of 17 non cancer atherosclerotic subjects 9 women and 8 men, of mean age and age range similar to the above were also studied for comparison. The R index (the total count rate in bone metastases divided by the total count rate in a contralateral area), the maximum semi-quantitative standardized uptake value (SUVmax) of BS lesions and the mean number of metastases were evaluated. For the metastatic findings in the PET/CT scans the automatic method of contouring with 50% background cut-off was used, while for the 99mTc-MDP BS metastases were delineated manually. RESULTS: The mean R index of the bone metastatic foci studied by 18F-FDG PET/CT was 1.89±0.69 for Groups I and II patients. There was no significant difference of the R index between prostate cancer and breast cancer metastases (1.95±0.86 vs 1.83±0.52). The average SUVmax value was significantly higher in breast cancer patients than in prostate cancer patients (5.15±2.54 vs 4.01±1.71; P<0.05). There was no significant correlation in both cancer groups between R index and SUVmax values. The number of metastatic foci diagnosed by the 99mTc-MDP BS scan was much less than by the 18F-FDG PET/CT. CONCLUSION: No significant correlation was noticed in the metabolic activity-glucose utilization of metastatic bone foci between breast and prostate cancer cases. This observation validates the independent value of analyzed diagnostic methods and suggests negligible influence of glucose utilization in bone re-modeling in the above metastatic cancer cells. The 18F-FDG PET/CT bone scan was much better in diagnosing metastases compared to the 99mTc-MDP scan.

An Unexpected and Less Recognized Altered Distribution on Bone Scintigraphy; Possibility of 99mTc-Dextrose Complex as a Cause.

Optimal performance of diagnostic tests and correct interpretation depend on multiple factors, one of which is proper radiopharmaceutical preparation. Unwanted impurities result in altered distribution of radiopharmaceuticals and then poor-quality or uninterpretable studies. Therefore, following the reconstitution steps according to standard and validated protocols by the technologist is mandatory. Here, we present 2 cases with unexpected and less recognized distribution of Tc-methylene diphosphonate on bone scintigraphy.

Spleen Uptake on a Bone Scan.

We present a patient with spleen uptake on bone scanning that was due to sickle cell disease. We also discuss other etiologies for this finding.

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

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis.

OBJECTIVES: To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. METHODS: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvß3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. RESULTS: Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvß3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. CONCLUSIONS: Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.