99mTc-methylene Diphosphonate Research Articles

Unexpected Artifact on 99mTc-Methylene Diphosphonate Bone Scintigraphy.

Asymmetric hot spots in the axial skeleton on bone scintigraphy may confound diagnosis. We describe an unexpected artifact of 99mTc-methylene diphosphonate near the breast in a 55-y-old woman with breast cancer. The initial whole-body bone scintigraphy revealed a solitary focal lesion in the anterior ribs on the left side. After careful tracking, we determined that this hot spot originated from the adhesive bandage. The patient had placed it in her left front pocket after removing it from the injection site. She was rescanned after the bandage had been removed from her pocket.

Myxofibrosarcoma of the Chest Wall Detected on 99mTc-MDP Whole-Body Bone Scan.

Myxofibrosarcoma is a type of soft tissue sarcoma, predominantly characterized by a high propensity for local recurrence, albeit demonstrating a relatively diminished risk for distant metastasis. Its prevalence is notably higher in elderly patients. Here, we present a case of a 73-year-old woman diagnosed with Myxofibrosarcoma. She was subjected to a whole-body bone scan using 99mTc-methylene diphosphonate (MDP) to survey potential bony metastasis. It revealed marked MDP accumulation with peripheral soft tissue uptake in the right lateral chest region of this patient. This imaging phenotype could potentially be attributed to the augmented vascularity within the tumor, a finding that was prominently displayed in this particular case.

Diagnosis and prognosis of abnormal cardiac scintigraphy uptake suggestive of cardiac amyloidosis using artificial intelligence: a retrospective, international, multicentre, cross-tracer development and validation study

The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. Pfizer.

Diffused Pulmonary Uptake of Tc-99m Methylene Diphosphonate Bone Scan in Patient with Prostate Cancer without Blood Test and Correlative/Cross-Sectional Imaging Abnormalities: A Case Report

Introduction: Bone scan using Tc-99m methylene diphosphonate (MDP) is a commonly used procedure for evaluating bone metastasis in cancer patients. Extra-osseous pulmonary uptake in bone scans is mostly an incidental finding and occurs in a multitude of disorders. Clinicians should be alert to any findings on clinical or complementary diagnostic tools. We presented a case of prostate cancer male patients who demonstrated diffuse pulmonary uptake on Tc-99m MDP bone scan without any blood test and correlative/cross-sectional imaging abnormality Case Presentation: An 80-year-old male with adenocarcinoma of the prostate with a Gleason score of 6 (3+3). The PSA level was 0.009. The patient had a history of recurrent atrial fibrillation (AF), postural dizziness, HTN, Gout, and chronic renal failure, but all of these comorbidities were under control. The patient underwent a bone scan to annually check for the presence of bone metastases. Three hours after administering 740 MBq Tc-99m MDP intravenously. The reports didn’t show any increased uptake that would indicate metastases in the bones. Instead, diffuse bilateral pulmonary uptake and a mild increase in cardiac uptake were present. On the same day, a computed tomography (CT) scan of the thorax revealed 3 micro-nodules in the right upper lung that were described as benign lesions, and a chest X-ray confirmed normal results. The patient’s laboratory results were within normal range, and there were no clinical lung symptoms or complaints. Considering the patient history of persistent AF, chronic renal failure, and a complaint of postural dizziness, the bone scan finding may indicate involvement of amyloidosis. The relationship between amyloidosis and cancer was also widely noted. Conclusions: Tc-99m MDP may play a role in evaluating amyloidosis involvement in an uncommon place such as the lungs. Future research should focus on analyzing diagnostic options in the patient’s condition in this situation. Keywords: cancer, diffused pulmonary uptake, amyloidosis, bone scan

Negative methylene diphosphonate scintigraphy in biopsy-confirmed hereditary transthyretin Ala117Ser cardiac amyloidosis: a case report

99mTc-pyrophosphate (99mTc-PYP) scintigraphy is highly sensitive and specific for the diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). Commonly used alternative tracers included 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP). A 61-year-old Chinese man presented with signs indicative of left ventricular hypertrophy. Genetic testing revealed heterozygous transthyretin Ala117Ser mutation. Scintigraphy using 99mTc-methylene diphosphonate failed to show myocardial uptake. Five months later, the patient underwent permanent pacemaker implantation. Tafamidis was used irregularly, and the patient died 2 years later. 99mTc-methylene diphosphonate may not be appropriate for diagnostic use in ATTR-CA patient with transthyretin Ala117Ser mutation.

Diagnostic value of whole -body diffusion weighted imaging added to bone scan in early diagnosis of bone metastases in breast cancer patients

BackgroundMetastases to the bones are a frequent location of metastasis in advanced breast cancer and are responsible for substantial morbidity and healthcare expenses. Imaging has been crucial in directing patient therapy for decades, contributing to the staging and response evaluation of the skeleton. This research aimed to assess the diagnostic value of whole-body magnetic resonance imaging with diffusion-weighted imaging added to radionuclide bone scans for early diagnosis of bone metastases in breast cancer patients.ResultsThe study was a prospective observational cohort study performed on 20 patients with breast cancer and suspected bone metastases. The patients were evaluated first by obtaining a detailed personal history. Laboratory tests, including CBC, liver, and kidney function tests were assessed. All patients were examined by diffusion-weighted whole-body MRI (DWIBS; diffusion-weighted imaging with background body signal suppression) images and bone scintigraphy after intravenous injection of 20 mci of technetium-99m (99mTc) methylene diphosphonate using a dual head gamma camera. The total number of lesions detected by bone scan was 74, and 75 lesions were seen by DWIBS. Twenty-four lesions were missed by bone scan and detected by DWIBS. Fourteen lesions were detected by bone scan and found free by DWIBS examination in the spine and pelvic bones.ConclusionsWhole body DWIBS seems to be a promising method of imaging in detecting bone metastases from breast cancer that could be used complementary to the traditional bone scan for more accurate diagnosis and staging of the tumor, helping to determine the most appropriate protocol of management.

An artificial intelligence framework for the diagnosis of prosthetic joint infection based on 99mTc-MDP dynamic bone scintigraphy.

Dynamic bone scintigraphy (DBS) is the first widely reliable and simple imaging modality in nuclear medicine that can be used to diagnose prosthetic joint infection (PJI). We aimed to apply artificial intelligence to diagnose PJI in patients after total hip or knee arthroplasty (THA or TKA) based on 99mTc-methylene diphosphonate (99mTc-MDP) DBS. A total of 449 patients (255 THAs and 194 TKAs) with a final diagnosis were retrospectively enrolled and analyzed. The dataset was divided into a training and validation set and an independent test set. A customized framework composed of two data preprocessing algorithms and a diagnosis model (dynamic bone scintigraphy effective neural network, DBS-eNet) was compared with mainstream modified classification models and experienced nuclear medicine specialists on corresponding datasets. In the fivefold cross-validation test, diagnostic accuracies of 86.48% for prosthetic knee infection (PKI) and 86.33% for prosthetic hip infection (PHI) were obtained using the proposed framework. On the independent test set, the diagnostic accuracies and AUC values were 87.74% and 0.957 for PKI and 86.36% and 0.906 for PHI, respectively. The customized framework demonstrated better overall diagnostic performance compared to other classification models and showed superiority in diagnosing PKI and consistency in diagnosing PHI compared to specialists. The customized framework can be used to effectively and accurately diagnose PJI based on 99mTc-MDP DBS. The excellent diagnostic performance of this method indicates its potential clinical practical value in the future. • The proposed framework in the current study achieved high diagnostic performance for prosthetic knee infection (PKI) and prosthetic hip infection (PHI) with AUC values of 0.957and 0.906, respectively. • The customized framework demonstrated better overall diagnostic performance compared to other classification models. • Compared to experienced nuclear medicine physicians, the customized framework showed superiority in diagnosing PKI and consistency in diagnosing PHI.

The 'Eye Mask Sign' in Fibrous Dysplasia on 99mTc-MDP Skeletal Scintigraphy and SPECT/CT.

Fibrous dysplasia (FD) is a fibro-osseous disorder that manifests with distinct or overlapping clinical patterns. FD may be monostotic or polyostotic and commonly associated with syndromes such as McCune-Albright syndrome and Mazabraud syndrome. We report a case of polyostotic FD with bilateral involvement of craniofacial bones in a distinct pattern and propose this characteristic appearance as the 'eye mask sign' on 99mTc-Methylene Diphosphonate (MDP) skeletal scintigraphy and SPECT/CT. Other unusual skeletal scintigraphic features noted in this case are also described (Figs. 1, 2, and 3).

Quantitative assessment of 99mTc-methylene diphosphonate bone SPECT/CT for assessing bone metastatic burden and its prognostic value in patients with castration-resistant prostate cancers: initial results in a single-center retrospective study

To evaluate the prognostic value of the quantitative assessment of 99mTc-methylene diphosphonate (99mTc-MDP) bone SPECT/CT in castration-resistant prostate cancer (CRPC) patients with bone metastases. A total of 103 patients who underwent 99mTc-MDP bone SPECT/CT imaging from the neck to the proximal femur were included. First, in 65 patients without bone metastases, the normal range of standardized uptake value (SUV) of non-pathological bone was evaluated to determine an SUV threshold to reliably exclude most normal osseous activity. Then, in 38 CRPC patients with bone metastases, lesion uptake volume (LUV), which is the extracted volume of bone metastases exhibiting high accumulation above the SUV threshold, was calculated. The relation between LUV and prostate-related mortality was statistically evaluated. Based on the SUV measurements of non-pathological bones, the optimal SUV threshold, which defines abnormal bone SPECT uptake, was determined to be 8. Median LUV was 39mL (interquartile range 4.0-104.3mL) in the CRPC subjects with bone metastases. Kaplan-Meier survival analysis showed a significant relation between prostate cancer-specific survival and LUV (cut-off value, 19.95mL; P = 0.001). Multivariate analysis revealed LUV as an independent prognostic factor for the survival (P = 0.008, hazard ratio 23.424). Global chi-square test showed that LUV had significant incremental prognostic value in addition to prostate-specific antigen and the interval from progression to CRPC until bone SPECT/CT (P = 0.022). Quantitative assessment of 99mTc-MDP bone SPECT images can provide valuable prognostic information in CRPC patients with bone metastases.

Comparison of 99m Tc-methylenediphosphonate and 68 Ga-BPAMD PET/computed tomography imaging in bone metastasis.

Bone is considered as the third most common site of metastases, besides lung and liver. Early detection of skeletal metastases aids in better management of skeletal-related events. In the present study cold kit-based 2,2 ' ,2 '' -(10-(2-((diphosphonomethyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (BPAMD) was labeled with 68 Ga. The radiolabeling parameters and clinical evaluation in patients with suspected bone metastases were compared with routinely used 99m Tc-methylenediphosphonate ( 99m Tc-MDP). The kit components of MDP were incubated with at room temperature for 10 min, followed by radiochemical purity testing using thin-layer chromatography. For radiolabeling of BPAMD, the cold kit components reconstituted in 400 μL of HPLC grade water were transferred and incubated with 68 GaCl 3 in the reactor vessel of the fluidic module at 95°C for 20 min. Radiochemical yield and purity were determined with instant thin-layer chromatography using 0.5 M sodium citrate as mobile phase. For clinical evaluation, patients ( n = 10) with suspected bone metastases were enrolled. 99m Tc-MDP and 68 Ga-BPAMD scans were performed on two different days in random order. Imaging outcomes were noted and compared. Radiolabeling of both tracers is facile using cold kit, although BPAMD requires heating. The radiochemical purity was observed to be greater than 99% for all preparations. Both MDP and BPAMD detected skeletal lesions; however, additional lesions were detected in total of seven patients which were not visualized clearly on 99m Tc-MDP scan. BPAMD can be easily tagged with 68 Ga using cold kits. The radiotracer is suitable and efficient for detection of bone metastases using PET/computed tomography.

A Bull’s Head Sign in SAPHO

A syndrome of synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) is a rare autoimmune disease. It occurs in genetically predisposed individuals by immune activation triggered by possible infectious agents. A 60-year-old man was presented with musculoskeletal and cutaneous manifestations. After exclusion of differential diagnoses, he was diagnosed with SAPHO and successfully treated with adalimumab. He had a typical image defined as a bull’s head sign in bone scintigraphy with 99mTcmethylene diphosphonate. Positron emission tomography also revealed increased inflammatory activity in related anterior chest joints and soft tissue. We want to emphasize diagnostic radiological images in patients with SAPHO to increase the awareness of clinicians.

Incidental Tc-99m MDP Uptake in Cortical-subcortical Parietotemporal Cerebral Area in a Patient with a History of Recent Ischemic Cerebrovascular Event who Underwent Whole-body Bone Scan.

The authors present Tc-99m methylene diphosphonate (MDP) uptake in the right parietotemporal area at whole-body bone scan (WBBS) in 75 years male patient with prostate adenocarcinoma Gleason score 3+4 (pT2N0Mx). No residual or metastatic disease was detected in the patient's Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography four months before WBBS. The patient had undetectable prostate-specific antigen levels and underwent WBBS to restage prostate cancer due to equivocal findings in previous WBBS. Current WBBS planar views revealed heterogeneous Tc-99m MDP uptake in the right parietotemporal area and the sphenoid bone in addition to equivocal uptake on the lower lumbar vertebrae. Single-photon emission computed tomography study to identify the MDP-avid lesion on the right cranial area revealed heterogeneous Tc-99m MDP uptake in the right parietotemporal area and sphenoid bone. The patient had a history of transsphenoidal surgery for a hypophyseal tumor two years ago and a recent cerebrovascular event (CVE). Diffusion-weighted magnetic resonance imaging revealed a cortical-subcortical patchy area of restricted diffusion in the parietotemporal region compatible with acute ischemia. Heterogeneous Tc-99m MDP uptake in the right parietotemporal area was attributed to recent CVE and secondary vascular-tissue change-related dystrophic calcification.

Intra-individual comparison of 18F-sodium fluoride PET–CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial

Detection of skeletal metastases in patients with prostate cancer or breast cancer remains a major clinical challenge. We aimed to compare the diagnostic performance of 99mTc-methylene diphosphonate (99mTc-MDP) single-photon emission CT (SPECT) and 18F-sodium fluoride (18F-NaF) PET-CT for the detection of osseous metastases in patients with high-risk prostate or breast cancer. MITNEC-A1 was a prospective, multicentre, single-cohort, phase 3 trial conducted in ten hospitals across Canada. Patients aged 18 years or older with breast or prostate cancer with a WHO performance status of 0-2 and with high risk or clinical suspicion for bone metastasis, but without previously documented bone involvement, were eligible. 18F-NaF PET-CT and 99mTc-MDP SPECT were done within 14 days of each other for each participant. Two independent reviewers interpreted each modality without knowledge of other imaging findings. The primary endpoint was the overall accuracy of 99mTc-MDP SPECT and 18F-NaF PET-CT scans for the detection of bone metastases in the per-protocol population. A combination of histopathological, clinical, and imaging follow-up for up to 24 months was used as the reference standard to assess the imaging results. Safety was assessed in all enrolled participants. This study is registered with ClinicalTrials.gov, NCT01930812, and is complete. Between July 11, 2014, and March 3, 2017, 290 patients were screened, 288 of whom were enrolled (64 participants with breast cancer and 224 with prostate cancer). 261 participants underwent both 18F-NaF PET-CT and 99mTc-MDP SPECT and completed the required follow-up for statistical analysis. Median follow-up was 735 days (IQR 727-750). Based on the reference methods used, 109 (42%) of 261 patients had bone metastases. In the patient-based analysis, 18F-NaF PET-CT was more accurate than 99mTc-MDP SPECT (84·3% [95% CI 79·9-88·7] vs 77·4% [72·3-82·5], difference 6·9% [95% CI 1·3-12·5]; p=0·016). No adverse events were reported for the 288 patients recruited. 18F-NaF has the potential to displace 99mTc-MDP as the bone imaging radiopharmaceutical of choice in patients with high-risk prostate or breast cancer. Canadian Institutes of Health Research.

Vertebral and ribs enhancement in Tc-99m methylene diphosphonate bone scan image by blind deconvolution algorithm.

The objective of the study was to restore Tc-99m methylene diphosphonate (MDP) bone scan image using blind deconvolution (BD) algorithm so that ribs, vertebrae, and lesions present in them become prominent. Our study consists of retrospective data in which 356 Tc-99m MDP bone scan images (178 anterior and 178 posterior) were processed using dynamic stochastic resonance algorithm, block-matching 3D filter, and then restored using BD algorithm. Two nuclear medicine (NM) physicians compared restored image with its input image; they especially lookedfor: (a) improvement in lesions detectability, (b) artifacts if any, (c) deterioration in ribs and vertebra, and (d) contrast enhancement in adjacent vertebra and adjacent ribs. They selected one out of two (restored and input) images, which had better quality. The overall image quality was also assessed using the following image quality metrics: brightness, blur, global contrast factor, and contrast per pixel. The Wilcoxon signed-rank test was applied for finding significant difference between the value of image quality metrics of restored image and input image at level of significance alpha = 0.05. According to NM physicians, 80.3% (286 out of 356) of restored images were acceptable, whereas 19.6% (70 out of 356) were unacceptable. Ribs and vertebrae were prominent in 161 out of 178 posterior restored images. Lumbar vertebrae were enhanced and well differentiated from adjacent vertebrae in 125 out of 178 anterior restored images. The value of image quality metrics of restored and input images were found to be significantly different ( P -value < 0.0001). Ribs, vertebrae, and lesions present in them become prominent in the most of Tc-99m MDP bone scan images (80.3%) restored using BD algorithm.

What's New in Musculoskeletal Tumor Surgery.

What's New in Musculoskeletal Tumor Surgery.

Adverse Clinical Events at the Injection Site Are Exceedingly Rare After Reported Radiopharmaceutical Extravasation in Patients Undergoing 99mTc-MDP Whole-Body Bone Scintigraphy: A 12-Year Experience.

The deleterious effects of high-dose radiation on normal tissue are sometimes extrapolated to diagnostic (SPECT and PET) radiopharmaceutical extravasation (RPE). It has been hypothesized that diagnostic RPE can have gradually evolving local tissue injury and a potentially increased risk of local dermatologic or oncologic diseases over a longer period. However, data on clinical adverse events after diagnostic RPE are limited. Therefore, our primary aim was to study the occurrence of short-term and long-term clinical adverse events in patients who underwent 99mTc-methylene diphosphonate (99mTc-MDP) whole-body bone scintigraphy (WBBS) with reported RPE. Methods: The records of 99mTc-MDP WBBS performed from June 2010 to January 2022 were retrospectively examined for RPE documented in the scan reports. The clinical records of patients with a documented RPE were extensively reviewed for any related short-term adverse events (within 2 wk of the WBBS: local symptoms and care sought for local dermatologic or musculoskeletal issues) and long-term adverse events (until the last follow-up: local deleterious effects and related consults for dermatology, plastic surgery, oncology, or orthopedics). Results: Retrospective review of the records of 31,679 99mTc-MDP WBBS studies showed RPE documented in 118 (0.37%). Medical records were not retrievable for 22 patients, yielding a final cohort of 96 patients with reported RPE. The median follow-up was 18.9 mo (interquartile range, 7.8-45.7 mo). Short-term events were noted in 4 patients, of whom one was asymptomatic. Of the 3 symptomatic patients, 2 experienced mild discomfort at the injection site, and 1 had tender swelling. Three of the 4 events were in patients who had a prior intravenous contrast extravasation for contrast-enhanced CT performed earlier during the day and a 99mTc-MDP injection later at the same site, likely leading to RPE. None of the long-term local events had any plausible link with the RPE event. Conclusion: Reported RPE was rare, and 3 patients (0.009%) had short-term local symptoms, all of which were likely related to the prior higher-volume intravenous contrast extravasation. The smaller-volume diagnostic radiopharmaceutical injections for WBBS are highly unlikely to cause local symptoms on their own. No patient had any long-term adverse event with a plausible link to the RPE.

A Case of Extracranial Metastasis of Glioblastoma Multiforme Seen on Bone Scintigraphy.

Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system in adults. It is known for its devastating intracranial progress thus attributing to its very short survival. Here, we report a case of 37-year-old female with GBM post surgery, chemotherapy and radiotherapy who presented with pain in right hip region. She was referred to our department for evaluation of skeletal metastasis. Tc-99m methylene diphosphonate bone scan revealed an expansile lesion involving the right iliac blade along with extensive lytic bony lesions throughout the axial skeleton.

New index to assess the extent of bone disease in patients with prostate cancer using SPECT/CT.

Assessing the extent of bone metastases in patients with prostate cancer is very important to predict patient prognosis. Therefore, the bone scan index (BSI), which is easy to use, has been used; however, the accuracy is not that high. In this study, we proposed a new index for the extent of bone disease using single-photon emission computed tomography with computed tomography (SPECT/CT) images and assessed the accuracy of calculation. In this study, a total of 46 bone scans from 12 patients with prostate cancer treated for bone metastases with Radium-223 were included. Whole-body planar images were obtained 150-180min after an intravenous injection of 99mTc-methylene diphosphonate, and cervical-to-pelvic SPECT/CT was immediately obtained. The total bone volume (TBV) and regional metabolic bone volume (MBV) were defined as Hounsfield unit of > 120, standardized uptake value (SUV) of > 0.5, and SUV of > 5-8 in four levels, respectively. Bone metabolism volumetric index (BMVI) was calculated as the percentage of the total MBV divided by TBV. The variability of the TBV measurement was evaluated by the percentage coefficient of variance (%CV) of TBV within individual patients. We evaluated the correlation of TBV with age, height, weight, and body mass index and the correlation and agreement between BSI and BMVI. The mean and %CV of TBV were 4661.7 cm3 and 2.8%, respectively, and TBV was strongly correlated with body weight. BMVI was significantly higher than BSI and correlated with alkaline phosphatase. For patients with progressive bone metastases, BSI was clearly underestimated, whereas BMVI was elevated. Although assessed in a small number of cases, the new index for assessing the extent of bone disease using SPECT/CT imaging was highly value than BSI and was significantly correlated with alkaline phosphatase. Therefore, this study suggests that BMVI could improve the low sensitivity of BSI in patients with low extent of disease grade.

ACTH-independent Cushing’s syndrome due to ectopic endocrinologically functional adrenal tissue caused by a GNAS heterozygous mutation: a rare case of McCune–Albright syndrome accompanied by central amenorrhea and hypothyroidism: a case report and literature review

In a small number of cases, the development of ectopic residual adrenal lesions during embryogenesis causing Cushing’s syndrome due to the production of excess cortisol has been reported. A 29-year-old woman was admitted to our hospital for fatigue and recent amenorrhea. Her plasma ACTH was <1.5 pg/mL, and her serum cortisol was 21.4 pg/mL after the 8 mg dexamethasone suppression test, revealing the presence of ACTH-independent Cushing’s syndrome; however, her bilateral adrenal glands were atrophied. Abdominal CT revealed a 40-mm round tumor on the right renal hilum and remarkably accumulated 131I-labelled adosterol. CT and bone scintigraphy showed that 99mTc-methylene diphosphonate had accumulated in her dissymmetric skull at the right-frontoparietal region. The tumor on the right renal hilum was laparoscopically removed. Her cortisol levels rapidly decreased to below the normal range, and glucocorticoids were administered to rescue adrenal insufficiency. The resected tumor was yellowish in appearance and 4.5×3.0×2.8 cm in size. Immunohistochemical staining for SF-1, P450scc, CYP17A, CYP21A, and CYP11B1 indicated that this tumor produced cortisol. Exome sequencing analysis revealed that the GNAS heterozygous mutation (c.601C>T, p. Arg201Cys; accession number, NM_000516.5) was found in approximately 20% of the adrenal tumor sample. A mutation of GNAS, encoding the Gsα subunit that mediates GPCR signaling, causes the constitutive activation of adenylyl cyclase, resulting in hypersecretion of hormones regulated by the GPCR. GNAS mutation is one of the major genetic causes of cortisol-producing adrenal tumors independent of ACTH secretion. Considering the combination of GNAS mutation with one of the typical clinical triad characteristics, fibrous dysplasia of bone, we diagnosed this patient with McCune–Albright syndrome accompanied by ACTH-independent Cushing’s syndrome caused by an ectopic residual adrenal tumor due to GNAS mutation. This case highlights that GNAS involves a previously unknown pathological mechanism in which inhibition of the natural elimination of remnant tissue leads to ectopic endocrine hypersecretion.

Prospective study of Na[18F]F PET/CT for cancer staging in morbidly obese patients compared with [99mTc]Tc-MDP whole-body planar, SPECT and SPECT/CT

Purpose This prospective study aims to assess the diagnostic test characteristics of Na[18F]F PET/CT for the skeletal staging of cancer in morbidly obese patients compared with 99mTc-methylene diphosphonate (MDP), whole-body planar (WBS), SPECT, and SPECT/CT acquisitions. Material and methods One hundred seventeen obese patients (BMI 46.5 ± 6.1 kg/m2 and mean age, 59.0 years; range 32–89 years) with BMI > 40 kg/m2 were prospectively enrolled and underwent [99mTc]Tc-MDP WBS, SPECT, SPECT/CT, and Na[18F]F PET/CT within two weeks for the osseous staging of a malignancy. Images were assessed qualitatively using a 3-point scale. Patient and lesion-based diagnostic test characteristics were estimated using an optimistic and pessimistic dichotomization method. Results Bone metastases were confirmed in 44 patients. Patient-based optimistic diagnostic test characteristics were (sensitivity, specificity, overall accuracy): Na[18F]F PET/CT (95.5%, 95.9%, 95.7%), [99mTc]Tc-MDP WBS (52.3%, 71.2%, 64.1%), SPECT (61.4%, 80.8%, 73.5%) and SPECT/CT (65.9%, 91.8%, 82.1%). Lesion-based optimistic diagnostic test characteristics were: Na[18F]F PET/CT (97.7%, 97.9%, 97.7%), [99mTc]Tc-MDP WBS (39%, 67%, 48.9%), SPECT (52.9%, 93.6%, 67.3%) and SPECT/CT (65.9%, 91.8%, 82.1%). There was no significant difference in the specificity of Na[18F]F and SPECT/CT. All other pairwise comparisons were significant (p<.001). ROC curve analysis showed a high overall accuracy of Na[18F]F with significantly higher AUCs for Na[18F]F PET/CT compared to [99mTc]Tc-MDP WBS, SPECT, and SPECT/CT on both patient and lesion-based analysis (p<.001). Moreover, Na[18F]F PET/CT changed patient management in 38% of patients. Conclusions Na[18F]F PET/CT may be the preferred imaging modality for skeletal staging in morbidly obese patients. The technique provides excellent diagnostic test characteristics superior to [99mTc]Tc-MDP bone scan (including SPECT/CT), impacts patient management, has an acceptable radiation exposure profile, and is well-tolerated. Further cost-effectiveness evaluations are warranted.