Extraosseous distribution of 99mTc-diphosphonates during bone scintigraphy: review of the literature with case series presentation.

PURPOSE: Technetium-99m (99mTc)-diphosphonates represent the most common radiopharmaceutical used for bone scintigraphy. Even if the uptake in bone tissue has been widely explored, atypical uptake could be seen in soft tissue malignancies during bone scintigraphy. Increased vascularization and endothelium permeability represent front-row players in the biodistribution of the tracer, albeit other causes have been identified such as trauma, necrosis, the presence of calcification in metastasis, the pH of the tissue and consequently the type of ion concentration. CONCLUSION: The aim of this paper is to summarize the state of art of atypical soft tissue uptake seen in cancer tissues. The research was conducted on PubMed. The analysis of the literature suggests that calcium metabolism and ionic saturation have a pivotal role in the biodistribution of bone tracers. This phenomenon ranks in a complex scenario that includes carcinogenesis and cancer environment aspects. We also report two cases in our Institution in which atypical uptake in cancer tissues was observed.

Iatrogenic Lung Microembolism Resulted in Extraosseous Uptake of 99mTc-MDP.

A 61-year-old woman diagnosed with left breast cancer underwent a bone scan for the evaluation of possible bone metastases. Multiple foci of elevated activity were noticed in the spine and pelvis. In addition, a focus of intense activity was observed in the right lung on the SPECT/CT images without corresponding anatomic abnormality.

Intense 99mTc-MDP Uptake in the Abdominal Soft Tissue Secondary to Subcutaneous Insulin Injection.

A 65-year-old woman with known breast cancer presented with lower back pain over 1 month. Multiple sclerotic foci of increased tracer uptake in the bones were noted on the Tc-MDP bone scintigraphy and SPECT/CT images, suggesting osteoblastic metastasis. Unexpectedly, symmetric Tc-MDP activity was visualized in the soft tissue near the umbilical area, corresponding to the sites of insulin injection.

Extensive Extramedullary Hematopoiesis in Thalassemia: Soft Tissue Uptake on 99mTc-MDP SPECT/CT.

We report the case of a 45-year-old man with thalassemia major referred for a bone scan as a workup for generalized bone pain. Tc-MDP SPECT CT showed multiple elongated soft tissue masses along the inner aspects of ribs and along both sides of dorsal spine with calcification and mild tracer uptake. There was also a large lobulated presacral soft tissue mass displacing the bladder and involving the adjacent pelvic bone. Biopsy of mildly avid tracer uptake in pelvic soft tissue mass was extramedullary hematopoiesis confirmed by biopsy.

Maximum standardized uptake value from quantitative bone single-photon emission computed tomography/computed tomography in differentiating metastatic and degenerative joint disease of the spine in prostate cancer patients.

OBJECTIVE: Qualitative interpretation in bone scan is often complicated by the presence of degenerative joint disease (DJD), especially in the elderly patient. The aim of this study is to compare objectively 99mTc-MDP tracer uptake between DJD and osseous metastases of the spine using semi-quantitative assessment with SPECT SUV. METHODS: Bone scan with SPECT/CT using 99mTc-MDP was performed in 34 patients diagnosed with prostate carcinoma. SPECT/CT was performed based on our institutional standard guidelines. SUVmax based on body weight in 238 normal vertebrae visualized on SPECT/CT was quantified as baseline. A total of 211 lesions in the spine were identified on bone scan. Lesions were characterized into DJD or bone metastases based on its morphology on low-dose CT. Semi-quantitative evaluation using SUVmax was then performed on 89 DJD and 122 metastatic bone lesions. As most of the bone lesions were small in volume, the effect of partial volume effect (PVE) on SUVmax was also assessed. The corrected SUVmax values were obtained based on the recovery coefficient (RC) method. RESULTS: The mean SUVmax for normal vertebrae was 7.08 ± 1.97, 12.59 ± 9.01 for DJD and 36.64 ± 24.84 for bone metastases. The SUVmax of bone metastases was significantly greater than DJD (p value < 0.05). To assess for diagnostic accuracy, receiver operating characteristic (ROC) curve was performed. The area under the curve (AUC) was found to be fairly high at 0.874 (95% CI 0.826-0.921). The cutoff SUVmax value ≥ 20 gave a sensitivity of 73.8% and specificity of 85.4% in differentiating bone metastases from DJD. The corrected SUVmax for both DJD and bone metastases was smaller with a mean of 6.82 ± 6.02 and 24.77 ± 20.61, respectively. The cutoff SUVmax value was also lower with a value of 10, which gave a sensitivity of 73.8% and specificity of 86.5%. CONCLUSION: SPECT SUVmax was significantly higher in bone metastases than DJD. Semi-quantitative assessment with SUVmax can complement qualitative analysis. A cutoff SUVmax of ≥ 20 can be used to differentiate bone metastases from DJD. Partial volume effect should be taken into consideration in the quantification of small lesion size.

Comprehensive molecular imaging of malignant transformation of giant cell tumour of bone reveals diverse disease biology.

Malignant transformation of giant cell tumour of the bone is extremely rare. In addition, bone transformation in giant cell tumour may occur in different phases. With conventional X-rays, CT scans or MRIs, it may be challenging to distinguish among different phases of bone transformation, normal bone, soft tissue disease and bone disease (benign vs malignant lesions) and changes in multiple organs such as lung, liver and lymph nodes unless every lesion is biopsied, which is not practical. Molecular imaging with different isotopes (Tc-99m phosphonate, 2-deoxy-2-(18F)fluoro-d-glucose and sodium fluoride-18) may help to better characterise the disease. We hypothesised that molecular imaging could offer qualitative and quantitative characterisation of all stages of bone formation, destruction, reactivity or neoplasia in a patient with giant cell tumour of the bone, and we present the first case of molecular imaging where bone formation was seen in multiple soft tissues, such as lungs, muscles, lymph nodes and liver.

99mTc-Methyl-Diphosphonate Binding to Mineral Deposits in Cultures of Marrow-Derived Mesenchymal Stem Cells in Osteogenic Medium.

IMPACT STATEMENT: The work is notable for describing a highly sensitive, quantitative, and nondestructive method for evaluating the in vitro amount of mineral accompanying different types of osteogenic differentiation of mesenchymal stem cells in a monolayer cell culture. What is so unique and useful about the method is that it has the potential to be used to define the kinetics of the differentiation process, reflected in the mineralization, without destroying the monolayer. Therefore, it remains intact for further experiments.

Intense 99mTc-MDP Activity in an Elongated Sagging Gallbladder With a Partially Calcified Gallstone.

Intense activity was noted in the right middle abdomen on whole-body Tc-MDP bone scan images, which were obtained in a 78-year-old woman who had back pain. Further SPECT/CT images demonstrated that the intense activity was located in an elongated gallbladder. Partially calcified gallstone was also revealed on SPECT/CT images. Unexpectedly, the gallbladder activity was from the radioactive bile inside the gallbladder lumen, whereas the partially calcified gallstone was relatively photopenic.

Liver uptake on bone scanning: a diagnostic algorithm.

In this report, we present a case of liver uptake seen on a bone scan that was due to diffuse metastatic disease from breast carcinoma. We discuss possible etiologies for the uptake and offer an algorithm to narrow the differential diagnosis.

Preclinical evaluation of imaging biomarkers for prostate cancer bone metastasis and response to cabozantinib.

BACKGROUND: Prostate cancer is incurable once it has metastasized to the bone. Appropriate preclinical models are lacking. The therapeutic efficacy of the multikinase inhibitor cabozantinib was assessed in an orthotopic xenograft model of castration-resistant prostate cancer (CRPC) bone metastasis using noninvasive, multimodality functional imaging. METHODS: NOD/SCID mice were injected intratibially with luciferase-expressing ERG (v-ets avian erythroblastosis virus E26 oncogene homolog) rearranged VCaP human prostate carcinoma cells. The response of VCaP xenografts (n = 7 per group) to cabozantinib was investigated using bioluminescence imaging and anatomical and diffusion weighted magnetic resonance imaging. This enabled quantitation of tumor volume and apparent diffusion coefficient (ADC). Bone uptake of technetium-methylene diphosphonate ((99m)Tc-MDP) was assessed by single-photon emission computed tomography. Ex vivo micro computed tomography was used to quantify bone volume and correlated with appropriate histopathology. Statistical significance was determined using the two-sided Mann-Whitney test or Wilcoxon signed rank test. RESULTS: VCaP xenografts were predominantly osteosclerotic with some osteolytic activity. Fluorescent in situ hybridization analysis confirmed retention of ERG oncogene rearrangements. Cabozantinib induced a statistically significant 52% reduction in tumor luminance (P = .02) and stasis in tumor volume after 15 days of treatment. Tumor ADC statistically significantly increased with cabozantinib and was associated with extensive necrosis (after 10 days, mean tumor ADC ± SD = 556±43×10(-6) mm(2)/s vs pretreatment ADC = 485±43×10(-6) mm(2)/s; P = .02 ). Tumor-associated uptake of (99m)Tc-MDP was statistically significantly reduced after 3 days of treatment (P = .02), sustained over 15 days treatment, and associated with a statistically significant (P = .048) reduction in bone growth on the tibial cortex, yet a highly statistically significant (P = .001) increase in trabecular bone volume. CONCLUSIONS: The intratibial VCaP model faithfully emulates clinical disease. Cabozantinib exerts potent effects on both tumor and tumor-induced bone matrix remodeling, and quantitation of ADC provides a clinically translatable imaging biomarker for early, sensitive assessment of treatment response in CRPC bone metastasis.

Disparities in uptake pattern of (123)I-MIBG, (18)F-FDG, and (99m)Tc-MDP within the same primary neuroblastoma.

We report an unusual case of primary neuroblastoma in an 11-year-old girl. The superior portion of the tumor accumulated I-MIBG, Tc-MDP, and F-FDG. In contrast, the inferior portion of the tumor showed no abnormal F-FDG or Tc-MDP uptake, which usually indicates tumor necrosis. This inferior portion of the tumor, however, had intense I-MIBG activity, consistent with viable tumor rather than tumor necrosis.

Myocardial uptake of 99mTc-HDP and reduced perfusion on CT in subacute myocardial infarction.

A 65-year-old man with known bone metastases from prostate cancer and no cardiac history attended for a restaging bone scan (BS). Diffuse increased Tc-HDP activity in the heart was noted, new since a BS 3 months earlier. A restaging contrast-enhanced CT scan on the same day showed reduced myocardial perfusion in the anterior, apical, and septal walls. On direct questioning, he described an episode of severe exertional chest pain the day before. Myocardial infarction was confirmed and treated with primary percutaneous coronary intervention. New cardiac uptake on BS, raising the possibility of myocardial infarction, is a red alert for clinicians.

Intense splenic 99mTc-MDP uptake in a patient with myelofibrosis.

99mTc-MDP bone scan was performed in a 49-year-old woman with breast cancer. Whole-body bone scan showed multiple foci of increased MDP activity in the bone and intense splenic 99mTc-MDP uptake. Initial bone marrow aspiration in multiple locations yielded no blood cells. A subsequent bone marrow biopsy in the left anterior superior iliac spine showed myelofibrosis in addition to the known bone metastasis.

99mTc-oxidronate uptake within urothelial carcinoma confirmed with SPECT/CT imaging.

A 63-year-old woman with recurrent urothelial carcinoma was referred for skeletal scintigraphy to evaluate for osseous metastatic disease. The bone scan showed no osseous metastatic disease, but did show intense focal radiotracer accumulation along the left aspect of the urinary bladder. SPECT/CT images localized this uptake to a calcified bladder wall mass corresponding with the biopsy-proven (via cystoscopy) recurrent tumor. This case demonstrates that (a) some tumors may accumulate radionuclide bone tracer, emphasizing the need for careful evaluation of nonosseous structures during bone scan interpretation; (b) SPECT/CT is useful for clarifying potentially confusing findings and preventing misdiagnosis.

Bilateral lung 99mTc-MDP uptake on the bone scintigraphy in the myelodysplastic syndromes (MDS).

We report a case of myelodysplastic syndrome (MDS) with unusual abnormal 99mTc-MDP activity throughout both lungs on whole-body bone scan. To explain the pancytopenia, bone marrow examination was carried out which showed hypocellularity in addition to large abnormal megakaryocytes indicating myelodysplastic changes. His whole-body bone scan showed increased 99mTc-MDP activity in both lungs, kidneys, and also along the proximal two thirds of the femora. It was concluded that lung uptake in addition to skeletal uptake on scintigraphic bone scanning should be kept in mind in patients with MDS.

Extraosseous bone tracer accumulation of the liver on 99mTc-HDP bone scintigraphy in intermittent bleeding after iatrogenic liver injury.

A 69-year-old man with common bile duct cancer and deep jaundice had complained of abdominal pain after percutaneous transhepatic biliary drainage. The laboratory workup showed reduction of serum hemoglobin level after the procedure. A 99mTc-hydroxy diphosphonate bone scan was performed for further evaluation of common bile duct cancer, and there was no abnormality of the skeletal structures. However, diffuse and hazy increased radiotracer uptake was detected on the liver. Follow-up contrast-enhanced 99mCT revealed hematoma and subcapsular hemorrhage of the liver.

Higher scrotal uptake ratio of (99m)Tc-MDP on bone scans in newly diagnosed prostate cancer: a reliable indicator of pelvic node metastasis.

OBJECTIVE: Pelvic lymph node dissection (PLND) is the gold standard procedure for nodal staging in prostate cancer (PC) but less commonly used due to its invasiveness. More commonly computerized tomography (CT) and magnetic resonance imaging (MRI) are used although these have limited sensitivities and specificities. The aim of this study was to find out the correlation between higher scrotal uptake ratio (SUR) of (99m)Tc-methylene diphosphonate (MDP) on bone scan and pelvic node metastasis in patients with PC at high risk for nodal metastasis. METHODS: This was a retrospective study which included 68 biopsy proven newly diagnosed PC patients who had bone scan from January 2008 till January 2012. MRI of the pelvis, prostate specific antigen (PSA) and Gleason's score were available in all patients. Whole body bone scan was performed in all patients and SUR was calculated by dividing mean counts over scrotum and soft tissue over lateral aspect of right thigh. PLND was carried out within 2-3 weeks of MRI study in these patients. RESULTS: Mean age of studied males was 71 ± 07 years with a mean PSA level of 65 ± 162 ng/ml. Prostate biopsy revealed adenocarcinoma in all patients with mean Gleason's score 7 ± 1. Mean SUR was 2.786 ± 0.496. MRI was positive for pelvic lymphadenopathy in 32/68 (47 %). PLND revealed evidence of nodal metastasis in 16/68 (24 %) patients. Receiver operating characteristic analysis revealed good diagnostic strength of SUR for nodal metastasis with a cut off value of >2.99 with an area under curve (AUC) 0.708 (95 % CI 0.533-0.847, p value <0.05) and a mean sensitivity of 68.75 % and mean specificity of 80 %. Diagnostic strength of MRI for nodal metastasis was found to be low (AUC 0.566, 95 % CI 0.047-0.657, non-significant p value). No significant correlation was found between SUR and PSA in nodes positive and nodes negative patients. CONCLUSION: We conclude that in newly diagnosed PC patients, higher SUR on bone scan has a high diagnostic accuracy for pelvic node metastasis. Furthermore, a bone scan with a SUR <2.99 and negative for bone metastasis can stratify newly diagnosed PC patients as low risk.