A Case of Metastatic Pulmonary Calcification Detected on 99mTc-MDP Bone Scan and 99mTc-FAPI Scan.

ABSTRACT: A 59-year-old woman with recent history of weakness, loss of appetite, and significant weight loss was referred for malignancy workup. On the first day, the patient underwent a 99mTc-MDP scan, which revealed diffuse pulmonary uptake in both lungs. Two days later, 99mTc-FAPI scan was performed and showed diffuse pulmonary uptake in the planar and SPECT/CT images. The study present an interesting case demonstrating FAPI-ligand uptake in metastatic pulmonary calcification.

Treatment of [99mTc]Tc-hydroxy-diphosphonate ([99mTc]Tc-HDP) extravasation using hyaluronidase.

Extravasation of 99mTc-labeled radiopharmaceuticals is generally considered to require no specific intervention. In the presented case, the use of hyaluronidase could have minimized the adverse effects resulting from such an extravasation. Currently, no guidelines exist regarding the use of hyaluronidase after extravasation of [99mTc]Tc-HDP. Considering the low risk of administering hyaluronidase, it should be considered to limit the risk of injury after extravasation of [99mTc]Tc-HDP.

Predicting the Prognosis of Prostate Cancer Bone Metastasis Using the Bone Scan Index and Hot Spots Calculated Using VSBONEⓇ Bone Scan Index from Tc-99m-Hydroxymethylene Diphosphonate Bone Scintigraphy.

INTRODUCTION: The bone scan index (BSI) is widely used as a quantitative indicator of bone metastasis, therapeutic effect assessment, and prognosis prediction in prostate cancer. However, the BONE NAVI, which calculates BSI, only supports bone scintigraphy using Tc-99m-methylene diphosphonate. We developed the VSBONEⓇ BSI, which calculates BSI from bone scintigraphy using Tc-99m-hydroxymethylene diphosphonate (HMDP). The purpose of this study was to demonstrate that the BSI calculated using VSBONEⓇ BSI and hot spots (HS), which indicates the number of abnormal accumulations, are useful prognostic factors for patients with prostate cancer bone metastasis, similar to BONE NAVI. METHODS: We analyzed 322 patients who underwent bone scintigraphy for prostate cancer bone metastasis at our hospital. Initial bone scintigraphy was performed using Tc-99m-HMDP. All cases were retrospectively examined for their outcome and time to the final outcome. The results obtained were compared with the BSI and HS calculated using VSBONEⓇ BSI. RESULTS: When the patients were divided into two groups, HS >2 and HS ≤2, the HS ≤2 group had a significantly longer survival time (p < 0.001). In addition, when divided into two groups, BSI >0.46 and BSI ≤0.46, the survival time of the BSI ≦0.46 group was significantly longer (p < 0.001). CONCLUSION: BSI and HS obtained using VSBONEⓇ BSI may be useful as prognostic predictors, similar to those obtained using BONE NAVI.

Assessment of in vivo bone activity patterns in medial mobile-bearing unicompartmental knee arthroplasty : a prospective SPECT/CT study.

AIMS: Higher osteoblastic bone activity is expected in aseptic loosening and painful unicompartmental knee arthroplasty (UKA). However, insights into normal bone activity patterns after medial UKAs are lacking. The aim of this study was to identify the evolution in bone activity pattern in well-functioning medial mobile-bearing UKAs. METHODS: In total, 34 patients (13 female, 21 male; mean age 62 years (41 to 79); BMI 29.7 kg/m2 (23.6 to 42.1)) with 38 medial Oxford partial UKAs (20 left, 18 right; 19 cementless, 14 cemented, and five hybrid) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively, and at one and two years postoperatively. Changes in mean osteoblastic activity were investigated using a tracer localization scheme with volumes of interest (VOIs), reported by normalized mean tracer values. A SPECT/CT registration platform additionally explored cortical tracer evolution in zones of interest identified by previous experimental research. RESULTS: Significant reduction of tracer activity from the preoperative situation was found in femoral and anteromedial tibial VOIs adjacent to the UKA components. Temporarily increased osteoblastic bone activity was observed in VOIs comprising the UKA keel structure at one year postoperatively compared to the preoperative activity. Persistent higher tracer uptake was found in the posterior tibial cortex at final follow-up. Multivariate analysis showed no statistical difference in osteoblastic bone activity underneath cemented or cementless components. CONCLUSION: Well-functioning medial mobile-bearing UKAs showed distinct changes in patterns of normalized bone tracer activity in the different VOIs adjacent to the prosthetic components, regardless of their type of fixation. Compared to the preoperative situation, persistent high bone activity was found underneath the keel and the posterior tibial cortex at final follow-up, with significant reduced activity only being identified in femoral and anteromedial tibial VOIs. Cite this article: Bone Joint J 2022;104-B(1):34-44.

Comparison of bone single-photon emission computed tomography (SPECT)/CT and bone scintigraphy in assessing knee joints.

BACKGROUND: This study attempted to compare the radiopharmaceutical uptake findings of planar bone scintigraphy (BS) and single photon emission computed tomography (SPECT)/computed tomography (CT) performed on knee joints. METHODS: We retrospectively included 104 patients who underwent bone SPECT/CT and BS 4 h after the intravenous administration of technetium-99m-hydroxymethylene diphosphonate (99mTc-HDP) for pain in the knee joint. The uptake degree of each of the knee regions (medial femoral, lateral femoral, medial tibial, lateral tibial, and patellar area) in planar images and SPECT/CT were evaluated by visual (grades 0 to 2) and quantitative analyses (uptake counts for planar image and standardized uptake values [SUVs] for SPECT/CT). RESULTS: The uptake grades assessed visually on the planar images differed significantly from the uptake grades on SPECT/CT images in all areas of the knee (all p < 0.001), and SPECT/CT imaging revealed a larger number of uptake lesions than those noted in planar imaging for each patient (3.3 ± 2.0 vs 2.4 ± 2.3, p < 0.0001). In all regions of the knee, all of the quantitative values, including uptake counts obtained from the planar image as well as the maximum SUV (SUVmax) and mean SUV (SUVmean) obtained from SPECT/CT, showed statistically higher values as their visual grades increased (all p < 0.001). However, when analyzed for each area, only the SUVmax showed a significant difference by grade in all knee regions. Quantitative uptake values obtained from planar images were moderately correlated with SUVs of SPECT/CT images (r = 0.58 for SUVmean and r = 0.53 for SUVmax, all p < 0.001) in the total knee regions. Looking at each area, there was a significant but low correlation between the uptake counts of the planar images and the SUVs on SPECT/CT in the right lateral tibial region (r = 0.45 for SUVmean, r = 0.31 for SUVmax, all p < 0.001). CONCLUSIONS: In assessing knee joints, the findings of planar images and SPECT/CT images differ both visually and quantitatively, and more lesions can be found in SPECT/CT than in the planar images. The SUVmax could be a reliable value to evaluate knee joint uptake activity.

Estimation of prevalence of transthyretin (ATTR) cardiac amyloidosis in an Australian subpopulation using bone scans with echocardiography and clinical correlation.

BACKGROUND: Bone scans differentiate transthyretin (ATTR) cardiac amyloidosis from light chain amyloidosis and other causes of increased left ventricular (LV) wall thickness. We examined the prevalence and implications of cardiac uptake in the general population. METHODS: Patients were included based on having undertaken a bone scan for non-cardiac indications using Technetium 99m hydroxymethylene diphosphonate (HMDP) or Technetium 99m methylene diphosphonate (MDP). Blinded image review was undertaken. Positive was defined as cardiac uptake ≥ rib AND heart/whole body ratio (H/WB) > 0.0388. Echocardiography and clinical records were reviewed. RESULTS: 6918 patients were included. 15/3472 HMDP scans were positive (14 males, 1 female): none in individuals aged < 65; 1.44% in males and 0.17% in females ≥ 65; 6.15% in males and 1.69% in females ≥ 85. Only 1/3446 MDP scans were positive. All HMDP positive patients had increased septal wall thickness on echocardiography. H/WB correlated positively with LV mass, and negatively with LV ejection fraction. No individual had an explanation other than ATTR for their positive scan. CONCLUSION: In this Australian subpopulation, the prevalence of positive bone scans consistent with cardiac ATTR is 0% in individuals aged < 65. Prevalence increased with age, reaching 6.15% in men ≥ 85. The amount of HMDP uptake correlated with echocardiographic features of more advanced cardiac involvement. MDP does not appear useful in ATTR.

Semi-quantitative indices of cardiac uptake in patients with suspected cardiac amyloidosis undergoing 99mTc-HMDP scintigraphy.

BACKGROUND: 99mTc-HMDP scintigraphy has proved its efficacy in non-invasive diagnosis of cardiac amyloidosis (CA) and is currently interpreted according to the Perugini qualitative assessment. Several semi-quantitative indices have been proposed to overcome inherent possible limitations of visual grading. Our aim was to comparatively evaluate six different indices and their diagnostic performance. METHODS: We retrospectively reviewed scintigraphy of 76 patients (53 ATTR, 12 AL, 11 LVH) who underwent diagnostic evaluation at our centre. ROC-curve analysis was performed to identify optimal cut-off and relative diagnostic accuracy of six different indices (of which one was proposed for the first time), both in identifying CA patients and in discriminating patients according to their Perugini score. RESULTS: Heart/Whole-body ratios proved to be the most accurate (100%) in identifying CA patients. Heart/Pelvis ratio (with soft tissue background correction) offered acceptable accuracy (98%), with the largest area under the curve (AUC) (0.98) in discriminating patients with Perugini ≥ 2. Heart/Contralateral Lung ratio confirmed to be exposed to confounding background noise in case of simultaneous lung uptake. Heart/Skull ratio had the worst performance, with six false-negative patients in ATTR identification. CONCLUSION: Heart/Whole-body ratios may be robust and effective semi-quantitative indices for the evaluation of CA by means of scintigraphy.

Value of antigranulocyte scintigraphy with Tc-99m-sulesomab in diagnosing combat-related infections of the musculoskeletal system.

AIM: Combat-related extremity injuries are regularly associated with long-term complications such as chronic infection, especially osteomyelitis. Clinical examination and laboratory parameters do not usually allow reliable diagnosis. In contrast, imaging techniques enable constructive assertions to be made about the location and extent of an infection of the peripheral musculoskeletal system. The aim of this study was therefore to determine the diagnostic reliability of three-phase bone scanning and antigranulocyte scintigraphy using Tc-99m-sulesomab (Leukoscan) in the diagnostic clarification of infections associated with combat-related extremity injuries. METHODS: Twenty-seven male patients (mean age 33.9 years) with suspected combat-associated infections of the extremities were included in this retrospective analysis. All patients underwent three-phase bone scanning using Tc-99m-HDP followed by antigranulocyte scintigraphy with Tc-99m-sulesomab. In 26 of the 27 patients, a CT scan of affected limb was obtained, where the secondary fusion with single photon emission CT data set was possible. The diagnostic reliability of imaging techniques was validated against microbiological samples obtained during surgery and used as gold standard. RESULTS: Three-phase bone scanning yielded a positive result in all patients, with 18 scans classified as true positive (TP) and nine scans as false positive (FP). This produced a sensitivity of 100%, a specificity of 0% and a positive predictive value (PPV) of 67%. Antigranulocyte scintigraphy recognised 13 patients as TP, 1 patient as FP, 8 patients as true negative (TN) and 5 patients as false negative (FN), which gave a sensitivity of 72%, a specificity of 88%, a PPV of 93%, a negative predictive value (NPV) of 62% and an accuracy of 78%. CT recognised in 7 cases a TP result, in 3 cases an FP, in 5 cases a TN and in 11 cases an FN result. This produced a sensitivity of 39%, a specificity of 63%, a PPV of 70%, an NPV of 31% and an accuracy of 46%. CONCLUSIONS: Three-phase bone scanning did not deliver any diagnostic benefit, since no result was able to differentiate unequivocally between infection-related and reactive changes. Antigranulocyte scintigraphy using Tc-99m-sulesomab represented a highly suitable technique for diagnostically clarifying combat-related infections of the extremities. It is superior to CT in sensitivity, specificity, PPV, NPV and accuracy.

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.

Increased focal bone tracer uptake at the popliteus muscle origin in primary TKA compared with revision TKA.

OBJECTIVE: The purpose of the study was to investigate if the TKA design (cruciate retaining (CR), posterior stabilized (PS), revision prostheses) had an influence on the bone tracer uptake (BTU) pattern at the origin of the popliteus muscle. MATERIALS AND METHODS: A total of 92 knees (male:female = 46:46) which had undergone prior TKA were included in this retrospective study, comprising the following 3 groups: (i) CR primary TKA (n = 45); (ii) PS primary TKA (n = 24); (iii) revision TKA (n = 23). All patients received a SPECT/CT after TKA surgery. SPECT/CT images were reviewed for the presence of BTU in the lateral femoral condyle (origin of the popliteus muscle) by two observers using Syngo.via software (Siemens Healthcare, Erlangen, Germany). The observers recorded the BTU pattern qualitatively in the lateral femoral condyle as either (i) absent; (ii) present and diffuse; and (iii) present and focal in the region of the popliteus muscle origin. RESULTS: In patients with a CR and PS design, focal increased BTU at the origin of the popliteus muscle was found in 80.0% and 83.3% respectively. Diffuse BTU was the predominant finding in patients with revision TKA (60.9%). The patterns of BTU did not show significant differences between the CR and the PS design. However, patterns of BTU differed significantly between primary TKA designs and revision TKA (p < 0.001). CONCLUSION: Differences in patterns of BTU at the popliteus muscle origin between primary TKA and revision prosthesis may be the result of decreased insertional tensile forces of the popliteus muscle after revision surgery due to increased stability provided by the revision design.

Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis.

OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation. BACKGROUND: Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations. METHODS: A total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)-diphosphonate (DPD) or 99mTc-hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini's method. RESULTS: Among 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings. CONCLUSIONS: The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.

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.

Tc-99m hydroxymethylene diphosphonate SPECT/CT for the evaluation of osteonecrosis of the jaw: preliminary study on diagnostic ability of maximum standardised uptake value.

AIM: To investigate the diagnostic ability of maximum standardised uptake value (SUVmax) at combined single-photon-emission computed tomography/computed tomography (SPECT/CT) for the evaluation of osteonecrosis of the jaw. MATERIALS AND METHODS: Seven patients with mandibular osteonecrosis (three osteoradionecrosis, three medication-related osteonecrosis of the jaw (MRONJ), and one rheumatoid arthritis) underwent SPECT/CT at 4 hours after injection of technetium 99m hydroxymethylene diphosphonate. The SPECT/CT parameters SUVmax were compared for the osteonecrosis with normal mandible. Statistical analyses among the SUVmax of osteonecrosis were performed by one-way repeated measures analysis of variance with Tukey's HSD (honestly significant difference) test. A p-value <0.05 was considered statistically significant. RESULTS: SUVmax for MRONJ and rheumatoid arthritis (23.24±8.63) were significantly higher than those for osteoradionecrosis (9.05±1.39, p=0.005) and normal mandible (3.57±0.46, p=0.000). CONCLUSIONS: SUVmax derived from bone SPECT/CT could be useful for the evaluation of osteonecrosis of the jaw.

Prediction of femoral head avascular necrosis following femoral neck fracture: "pin-tract sign" of 99mTc-HDP pinhole bone scan after metallic fixation.

OBJECTIVE: To evaluate the predicting value of 99mTc-hydroxydiphosphonate (HDP) pinhole bone scan in development of osteonecrosis of femoral head (ONFH) in patients with femoral neck fracture after cannulated screw fixation. METHODS: Pinhole bone scan of patients with metallically fixed femoral neck fracture from 2001 to 2015 were retrospectively reviewed. Initial pinhole bone scan was obtained within 2-3 weeks after surgery. Findings of initial pinhole bone scan were divided in to 4 groups. Group CU included cold defect in affected femoral head, group HU with no cold defect. Group PP with increased uptake along the inserted screws and group PN with no increased uptake along the inserted screws. More than 6 months of follow-up with pinhole bone scan and clinico-radiological evidence for ONFH was reviewed. RESULTS: 72 patients (mean age 54.01 years, male 22, female 50) were included. 19 patients were in group CU, 53 in group HU. 60 patients were in group PP, 12 in group PN. During the follow-up, 13 patients were diagnosed as ONFH. 9 (47.36%) patients in group CU developed ONFH and 4 (7.5%) in group HU. 4 (6.66%) patients in group PP developed ONFH and 9 (75%) in group PN. CONCLUSIONS: To predict ONFH of femoral head followed by neck fracture, many imaging techniques with variable results were known. In this study, cold defect in early postoperative pinhole bone scans could predict ONFH, and loss of increased uptake along screw inserted site could be a strong indicative sign of ONFH. Further evaluation with a larger population is necessary.

Prediction of painful temporomandibular joint osteoarthritis in juvenile patients using bone scintigraphy.

The study aims to evaluate whether bone scintigraphy is effective in diagnosing temporomandibular joint (TMJ) osteoarthritis (OA) in juvenile patients. A retrospective study was conducted with 356 consecutive patients with TMJ-OA who were clinically assessed according to the Research Diagnostic Criteria for Temporomandibular Disorders. Patients were assigned to three groups based on their ages: Group 1: aged 12-16 years; Group 2: aged 17-19 years; and Group 3: aged 20 years. Additionally, we performed qualitative and quantitative analyses of bone scintigraphy images for the TMJ uptake ratio of the involved joint. The diagnostic rate of TMJ-OA (n = 356, 100%), and the overall presence of subjective pain (n = 282, 77.3%) was closest to the results of bone scintigraphy (n = 333, 91.2%). In addition, reported TMJ pain was significantly associated only with the results of bone scintigraphy and not with the results of panoramic radiography or cone beam computed tomography (CBCT) in all age groups. With CBCT as the reference standard, the optimal cutoff values of the uptake ratio for the diagnosis of TMJ-OA were 2.171 and 2.017 in Groups 1 and 2, respectively (P value < 0.05). Our results suggest that bone scintigraphy can be considered a useful modality for diagnosing TMJ-OA in juvenile patients.

Renal Infarction and Its Consequences for Renal Function in Patients With Cardiac Amyloidosis.

OBJECTIVE: To describe the prevalence of and risk factors for renal infarction (RI) in patients with cardiac amyloidosis. PATIENTS AND METHODS: We evaluated 87 patients with cardiac amyloidosis who underwent renal technetium-99m-labeled dimercaptosuccinic acid scintigraphy in the Amyloidosis Referral Center of Henri-Mondor Hospital from October 1, 2015, through February 28, 2018. RESULTS: Three groups of patients were identified according to the underlying amyloidosis disorder: AL amyloidosis in 24 patients, mutated-transthyretin amyloidosis in 24 patients, and wild-type transthyretin amyloidosis in 39 patients. Patients with wild-type transthyretin amyloidosis were older (P<.001), more likely to be men (P=.02), to have arrhythmic heart diseases (P<.001), and to be receiving anticoagulation treatment (P<.001). Patients with AL amyloidosis had significantly higher N-terminal pro-B-type natriuretic peptide levels (P=.02) and were more likely to have nephrotic syndrome (P<.001). Renal infarction was detected in 18 patients (20.7%), at similar frequencies in the various groups. Baseline urinary protein to creatinine ratio was the only parameter for which a significant difference (P=.03) was found between patients with and without RI diagnoses. The likelihood of RI diagnosis was 47.1% (8 of 17) in the presence of AKI and 14.5% (10 of 69) in its absence (P=.003). Overall, heart transplant-censored patient survival did not differ significantly between patients with and without RI (P=.64), but death- and heart transplant-censored renal survival was significantly lower in patients with RI (P<.001). CONCLUSION: Our study suggests that prevalence of RI in patients with cardiac amyloidosis is higher than previously thought, regardless of the underlying amyloidosis disorder. Acute kidney injury in a patient with cardiac amyloidosis should alert clinicians to the possibility of RI.