Radiologic follow-up and prognosis of efficiency of systemic Sr-89 Cl-2 therapy of bone metastases in prostate cancer

We evaluated possibilities of bone scintigraphy with 99mTc-methylendiphosphonate (99mTc-MDP) and magnetic resonance imaging (MRI) in follow-up and prediction of effect in patients with extensive bone metastatic disease treated with betha-emitter 89SrCl2. 24 patients with prostate cancer and extensive metastatic involvement of skeleton were referred for the study. 89SrCl2 was injected as single injection of 150 MBq (4 mCi), in eighteen from Amersham plc., England, as Metastron, in six--from Medradiopreparat, Russia). In all patients bone scintigraphy with 99mTc-MDP and MRI study of metastatic regions were performed before and in 3 months after 89SrCl2 injection. Patients treated with Metsatron were also studied in 6 months after injection. Quantitative analysis of data comprised count and anatomic dimensions of metastatic areas and calculation of indices [metastasis/intact bone] both for scintillation count of 99mTc-MDP bone scans and signal intensity of T1-weighted MRI scan. Henceforth, we conclude the data of bone scanning with 99mTc-MDP and of MRI give evidencies for significant regress of bone metastases in patients treated with 89SrCl2 besides symptomatic suppression of pain syndrome. 99mTc-MDP bone scanning is also of predictive value for the prognosis of therapeutic effect of systemic radiotherapy with 89SrCl2 in prostate cancer.     

Apport de la scintigraphie au 99mTc-dépréotide pour le diagnostic de lésions osseuses secondaires dans le cancer bronchopulmonaire non à petites cellules stade III–IV

ObjectiveIn non-small cell lung cancer (NSCLC), metastatic bone involvement is usually assessed using conventional ^99mTc-HMDP bone scintigraphy, which has a high sensitivity but a poor specificity. The purpose of this study was to assess the usefulness of the ^99mTc-D scintigraphy for the detection of malignant bone metastases in patients with NSCLC stage III or IV and to compare these results with ^99mTc-HMDP bone scan findings.MethodsNineteen patients (13 M and 6 F, mean age 59 years) with proven NSCLC, suspected to have stage III or IV were enrolled prospectively. All patients underwent whole body ^99mTc-HMDP and ^99mTc-D scintigraphy to detect bone metastases within a mean interval of 14 days. Each focal uptake of ^99mTc-D or ^99mTc-HMDP was considered benign or malignant, leading to positive or negative diagnosis for bone involvement. The final diagnosis of bone metastases was established by a lung specialist, on the basis of additional imaging modalities and of 12 months follow-up.ResultsTwelve bone lesions were identified by ^99mTc-D scintigraphy, 10 were classified as bone metastases and two were classified as inflammatory bone lesions. Four patients were metastatic. Fifty eight bone lesions were detected by ^99mTc-HMDP scintigraphy, 26 of whom were considered malignant, eight patients were thus considered metastatic. Thereby, the two nuclear medicine modalities were concordant for 13 patients, that is 68% of cases and were discordant for six patients, representing 32% of cases. Diagnostic sensitivity, specificity and accuracy of depreotide scintigraphy and ^99mTc-HMDP bone scintigraphy were 75% for both, 93.3 and 73.3%, and 89.5 and 73.3% respectively.ConclusionOur data suggest that depreotide scintigraphy with the same sensitivity, a better accuracy and specificity than those of ^99mTc-HMDP bone scan can detect metastatic bone lesions in patients with NSCLC suspected to have stage III or IV disease.     

TEP/TDM au fluorure (18F) de sodium pour la détection des métastases osseuses du cancer de la prostate. Description de l’étude Fluprostic de comparaison de la TEP/TDM au fluorure (18F) de sodium à l’IRM corps entier dans cette indication

Fluorodeoxyglucose (¹⁸F) or FDG, the radioactive glucose analogue which is the reference radiopharmaceutical in oncologic PET, is not well suited for the detection of prostate cancer metastases the glucose metabolism of which is usually only slightly enhanced. Fluoride (¹⁸F) accumulates into the cortical bone, rapidly and intensely in reaction to a bony metastasis. In 2008, it has been granted a marketing authorisation in France, including imaging bone metastasis of prostate cancer. We report original clinical cases to illustrate its diagnostic performance. Whole-body MRI is developing and can also detect bone metastases. Recently diffusion-weighted MRI (DWI) has been proposed to increase the detection rate of metastases of the axial skeleton, which are largely predominant in prostate cancer. Using either hybrid PET/CT or MRI requires mobilising equipments, which are less available and more expensive than the gamma-cameras for classical bone scintigraphy, in the aim to achieve superior diagnostic performance. A clinical study protocol (STIC) has just been accepted for public funding. It aims to assess the impact on patient management of the discovery of the first macroscopic bony metastasis and the efficacy of diagnostic strategies including those innovations, individually and in association. In case of prostate cancer with a high risk of metastasis, but without any proven bone metastasis and no typical pattern on bone scintigraphy, fluoride (¹⁸F) PET/CT will be performed as well as whole-body MRI. Histopathology and/or data of a 6-month follow-up will be the standard of truth to evaluate the adequacy of impact on patient management and the benefit / cost ratio of those examinations. With this prospective national study, we hope to demonstrate in the real world a clinical role for this radiopharmaceutical, which was proposed several decades ago, but benefits from a renewed interest thanks to the development of PET/CT imaging.     

Radioisotopic Bone Scintigraphy with the Gamma Camera in the Investigation of Prostatic Cancer

Experience with x-rays, strontium-87m scintigraphy, and technetium-99m polyphosphate scintigraphy in the identification of bone metastases in 201 patients with prostatic cancer is reviewed. About 40% of the patients had demonstrable metastases in bone at the time of first presentation.Comparative studies of 247 x-ray and ^87mSr surveys indicated that x-rays failed to detect metastases in 10% of cases where they were identified by ^87mSr but that the isotopic survey similarly failed to detect radiologically evident deposits in 7% of cases.Similar studies comparing ^99mTc polyphosphate surveys with x-ray scans showed that x-rays missed isotopically detected metastases in 12% of cases, but in only one survey out of 67 did the isotope miss radiologically evident deposits. In a series of 32 patients investigated by both isotopic techniques ^99mTc polyphosphate did not fail to detect any metastases and identified deposits in one patient in whom they were missed by ^87mSr scintigraphy. About 15% of both x-ray and ^87mSr surveys gave equivocal results, but only 3% (2 out of 67) of ^99mTc polyphosphate surveys were equivocal.We concluded that ^99mTc polyphosphate bone scintigraphy with the gamma camera was the most reliable of the techniques used for the identification of bone metastases in patients with carcinoma of the prostate. The results of scintigraphy with ^87mSr suggested that serial surveys may provide early evidence of hormone resistance in prostatic cancer.     

The role of scintigraphy with the use of 99mTc-HYNIC-TOC in the diagnosis of medullary thyroid carcinoma

INTRODUCTION: Recently a new somatostatin analogue labelled with (99m)Tc ((99m)Tc-HYNIC-TOC) has been synthetized. Aim of this study was to evaluate the utility of (99m)Tc-HYNIC-TOC in the radionuclide imaging in patients with medullary thyroid carcinoma (MTC). MATERIAL AND METHODS: 30 patients with MTC aged 22-83 years in different stages of the disease were investigated. In 6 patients (group 1) scintigraphy was performed before surgery directly after diagnosis of MTC. Four patients (group 2) were qualified to the study in the phase of remission after surgical treatment that had been confirmed by low concentrations of calcitonin. Twenty patients (group 3) were investigated due to stagnation or recurrence confirmed by persistent hypercalcitoninemia. The scintigraphy using (99m)Tc-HYNIC-TOC (Tektrotyd, POLATOM) was performed 2 and 4 hours post injection of 20 mCi (740 MBq) of the tracer. Other imaging techniques were also employed and analysed in individual cases (US, CT, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-octreotide and FDG-PET). RESULTS: Images obtained 2 and 4 hours p.i. were similar. In group 1, uptake of the tracer was found in the primary tumour of MTC in all patients. In group 2, a false positive result was found in 1 of 6 patients. In the remaining 5 of 6 cases no pathological foci were visualised. In group 3, uptake in the thyroid bed was found in 3 of 20 cases and in the lymph nodes in 14 of 20 patients. In 3 of 20 cases uptake in the bone metastases was found. Globally, sensitivity of the scintigraphy using (99m)Tc-HYNIC-TOC was 86.4%, specificity - 75.0%, and accuracy - 84.6%. CONCLUSION: The scintigraphy using (99m)Tc-HYNIC-TOC showed high utility in the diagnosis of MTC. Confirmation of the presence of somatostatin receptors with this method may be used for treatment planning: surgery or radionuclide therapy.     

Regional blood flow and bone uptake of methylene-diphosphonate-technetium-99m

Sudeck's atrophy of the foot is an acute, patchy osteoporosis that, on bone scan, shows an increase in both bone blood flow and local bone uptake of bone-seeking radionuclides. The purpose of this study was to evaluate the relationship between bone uptake of 99mTc-MDP and local bone blood flow. In some patients with Sudeck's atrophy of one foot we measured local bone blood flow and bone uptake of 99mTc-MDP. External counting of radioactivity, with a count-rate of 1 second was performed for 60 minutes after i.v. injection of a known dose of 99mTc-MDP in some patients with Sudeck's atrophy of the foot. The regions of interest (ROI) were selected on the basis of a bone scan performed 24 hours earlier. We assumed that the data recorded during the first seconds (7-10) reflect local blood flow and the data at 60 minutes reflect the bone uptake. The ratio between the local blood flow in the involved and healthy foot was higher than the local bone uptake ratio. The ratio between bone uptake and local bone blood flow was higher in the normal foot than in the affected one. These results suggest that the bone avidity for bone-seeking radionuclides is lower in Sudeck's atrophy than in normal bone.     

Skeletal Scintigraphy

Skeletal scintigraphy, using phosphates or diphosphonates labeled with technetium 99m, is a sensitive method of detecting bone abnormalities. The most important and most frequent role of bone scanning is evaluating the skeletal areas in patients who have a primary cancer, especially a malignant condition that has a tendency to spread to bone areas. The bone scan is superior to bone radiographs in diagnosing these abnormalities; 15 percent to 25 percent of patients with breast, prostate or lung cancer, who have normal roentgenograms, also have abnormal scintigrams due to metastases. The majority of bone metastases appear as hot spots on the scan and are easily recognized. The incidence of abnormal bone scans in patients with early stages (I and II) of breast cancer varies from 6 percent to 26 percent, but almost invariably those patients with scan abnormalities have a poor prognosis and should be considered for additional therapies. Progression or regression of bony lesions can be defined through scanning, and abnormal areas can be identified for biopsy. The incidence of metastases in solitary scan lesions in patients with known primary tumors varies from 20 percent to 64 percent. Bone scintigraphy shows positive uptake in 95 percent of cases with acute osteomyelitis. Stress fractures and trauma suspected in battered babies can be diagnosed by scanning before there is radiological evidence. The procedure is free from acute or long-term side effects and, except in cases of very young patients, sedation is seldom necessary.Although the test is sensitive, it is not specific and therefore it is difficult to overemphasize the importance of clinical, radiographic, biochemical and scanning correlation in each patient.     

Cancer and bone repair mechanism: clinical applications for hormone refractory prostate cancer

It is a long-standing clinical observation that the bone corresponds to the prevalent site for metastatic growth of prostate cancer. In addition, bone metastases of this malignancy produce a potent blastic reaction, in contrast to the overwhelming majority of other osteotropic neoplasms, whose metastases are generally associated with an osteolytic reaction. Osteoblastic metastases represent almost always the first and, frequently, the exclusive site of disease progression to hormone refractory stage, stage D3. Moreover, the number of skeletal metastatic foci is the most powerful independent prognostic factor associated with a limited response to hormone ablation therapy and poor survival of advanced prostate cancer. It is noteworthy that disease progression to hormone refractory stage occurs almost always in osteoblastic metastases. These clinical observations suggested that the osteoblastic reaction is possibly not an innocent bystander of the metastatic prostate tumour growth, simply suffering its consequences, but it may in fact facilitate the efforts of metastatic cells to expand their population. An extensive line of research in the pathophysiology of osteoblastic metastases has established that the local blastic reaction involves the uPA/plasmin/IGF/IGFBP-3/TGFbs bioregulation system which can stimulate both the growth of osteoblasts and prostate cancer cells. Furthermore, we were the first to characterize osteoblast-derived 'survival factors' able to rescue metastatic prostate cancer cells from chemotherapy-induced apoptosis. These data resulted in the development of a novel concept of an anti-survival factor therapy, namely an anti-IGF-1 therapy, which has provided encouraging preliminary data in a phase II clinical trial with terminally-ill hormone/chemotherapy-resistant prostate cancer patients.     

Role of bone morphogenetic proteins in human prostate cancer pathogenesis and development of bone metastases: immunohistochemical study

Bone morphogenetic proteins (BMP) have the ability to induce ectopic bone formation. The findings of their expression in prostate cancers have been linked with specifically tumor progression to bone and development of osteosclerotic metastases. We investigated the expression pattern of BMP-2/4, -6 and -7 and the receptors BMPR-IA,-IB and -II in normal human prostate, organ-localized and metastatic prostate cancers. The expression we also examined in skeletal metastases caused by prostate cancer. In localized prostate cancers we found increased expression of BMP-6 and decreased expression of BMP-2/4 and -7. In metastatic prostate cancers the expression of examined BMPs decreased. The expression of BMPRs showed the tendency to be lower with progression of prostate cancer but the expression of BMPR-II was completely absent in metastatic prostate cancers. In bone metastases caused by prostate cancer we found high expression of BMP-2/4, -6 and -7. Decreased expression of BMPs and lose of BMPR-II expression, could suggest that the influence of BMPs on prostate cancer cells is inhibited and plays an important role in prostate cancer pathogenesis. High expression of osteogenic BMPs in prostate cancer bone metastases could explain their osteosclerotic properties.     

Distribution Features of Skeletal Metastases: A Comparative Study between Pulmonary and Prostate Cancers

Bone scintigraphies are widely applied for detecting bone metastases. The aim of this study was to investigate distribution features of bone metastases in pulmonary and prostate cancers. Bone scintigraphies were performed in 460 patients with pulmonary cancer and 144 patients with prostate cancer. Patients were divided into three groups according to the total number of bone metastases: few bone metastases, moderate bone metastases, and extensive bone metastases. We compared the distribution of bone metastases in the two cancers, and analyzed the relationship between the distribution of metastatic lesions and their metastatic patterns. A total of 2279 and 2000 lesions of bone metastases were detected in 258 patients with pulmonary cancer and 102 patients with prostate cancer, respectively. In patients with few bone metastases, the distributions of metastatic lesions in the vertebrae (χ² = 16.0, P = 0.000) and thoracic bones (χ² = 20.7, P = 0.002) were significantly different between pulmonary and prostate cancers. In cases with moderate bone metastases, the distributions in the vertebrae (χ² = 6.6, P = 0.010), pelvis (χ² = 15.1 P = 0.000), and thoracic bones (χ² = 38.8, P = 0.000) were also significantly different between the two cancers. However, in patients with extensive bone metastases, the distributions were very similar. As the total number of bone metastases increased, their distribution in pulmonary cancer did not noticeably change, but the distribution in the vertebrae and thoracic bones of prostate cancer patients significantly changed. Accordingly, the distribution characteristics of bone metastases differed in pulmonary and prostate cancers, mainly in the early stages of metastasis.     

Imagerie hybride (TEMP/TDM,TEP/TDM) et cancer différencié de la thyroïde

Differentiated thyroid cancer (DTC) is generally associated with a good prognosis. Local recurrences, mainly lymph-node involvement, account for 15–20% of cases and are surgically treated. Distant metastases, mostly in lungs and more rarely in bones, are present in 5% of patients. When iodine uptake is sufficient (in approximately 60% of patients), distant metastases can be destroyed by iterative activities of iodine 131. Serum thyroglobulin (Tg), which can be assessed either on hormonal treatment or on TSH stimulation is considered as the tumour marker in DTC. Functional (iodine 131 scintigraphy, FDG PET, bone scintigraphy) or anatomical (neck ultrasound, thoracic CT, bone MRI) imaging methods can be performed when Tg increases in order to show residual/recurrent disease. In recent years, new hybrid equipments integrating both a gamma camera and CT scan (SPECT/CT) have been commercialized while positron emission tomography cameras associated with CT (PET/CT) have been installed on the whole French territory. These equipments, which allow us to directly correlate functional and anatomical images, greatly improve the interpretation of planar scintigraphy or that of PET alone. Hybrid imaging enables us to precisely localize scintigraphic foci and most often, to immediately verify whether they correspond to tumour lesions. The aim of this article is to review the role of SPECT/CT and PET/CT in the management of patients with DTC in 2010.     

Intérêt de la TEMP-TDM dans le repérage des métastases chez les patients suivis pour cancer différencié de la thyroïde (À propos d’un cas)

It is very important in the management of patients with differentiated thyroid cancer (CDT) to precisely localize the foci of I-131 uptake, but it is difficult with planar scintigraphy only because of a lack of anatomic landmarks. In this context hybrid-imaging appears to be a preferred technique to overcome this deficiency. We report a case of metastatic follicular thyroid carcinoma (CDT) in which planar scintigraphy diagnosed multiples uptake abnormalities. The foci of I-131 pinpointed in abdominal cavity could not be identified anatomically on whole body scintigraphy. SPECT-CT imaging helped to locate these hot spots and assign them to hepatic localization.     

Apport de la médecine nucléaire dans la prise en charge du cancer de la prostate : analyse de 360 cas en milieu camerounais

Prostate cancer is the most frequent neoplasm affecting males above 50 years old in developed countries. Previous studies carried out in Cameroon have shown that, this condition is not infrequent. Late diagnosis is equally common. The advent of nuclear medicine technology in the year 2000 has enabled the possibility of prostate specific antigen (PSA) assay and imaging by bone scintigraphy. In this study, we aimed at assessing the contributions of PSA assay and bone scintigraphy in the management of prostate cancer in Cameroon. Within a 5 years period (January 2003–December 2007) 360 patients had biopsy proven (Gleason score) prostate adenocarcinoma. The age ranged from 50 to 85 years with a mean of 67 years. Those aged between 60 to 69 years were more affected. The patients were divided into 2 groups: a first one accruing of 250 patients with a previous bone scintigraphy carried out before treatment and a second group of patients who underwent a bone scintigraphy during treatment. Clinical features digital rectal examination, endorectal echography were noted. PSA levels and bone scintigraphy results were also noted. Most of these patients (80.56%) presented with advanced lesions with metastases. Orchiectomy and hormonotherapy were the most used methods of treatment due to late diagnosis. Bone scintigraphy-evidenced lesions were mainly located (92.25%) at the dorso-lombar region of the spine. There is a correlation between the following variables: clinical features, namely, digital rectal examinations, PSA blood levels, ultrasound, histology and bone scintigraphy. Therefore, we can conclude that, PSA is an important marker of prostate cancer. Its association with bone scintigraphy is appropriate for the detection of bone metastases.     

Notch signaling and ERK activation are important for the osteomimetic properties of prostate cancer bone metastatic cell lines

Prostate cancer bone metastases are characterized by their ability to induce osteoblastic lesions and local bone formation. It has been suggested that bone metastatic prostate cancer cells are osteomimetic and capable of expressing genes and proteins typically expressed by osteoblasts. The ability of preosteoblasts to differentiate and express osteoblastic genes depends on several pathways, including Notch and MAPK. Here we show that notch1 expression is increased 4-5 times in C4-2B and MDA PCa 2b cells (osteoblastic skeletal prostate metastatic cancer cell lines) when compared with nonskeletal metastatic cell lines (LNCaP and DU145). Notch1 ligand, dll1, is expressed only in C4-2B cells. Immunohistochemical studies demonstrate that Notch1 is present in both human clinical samples from prostate cancer bone metastases and the C4-2B cell line. To determine whether prostate cancer bone metastases respond to osteogenic induction similar to osteoblasts, C4-2B cells were cultured in osteogenic medium that promotes mineralization. C4-2B cells mineralize and express HES-1 (a downstream target of Notch), an effect that is completely inhibited by L-685,458, a Notch activity inhibitor. Furthermore, osteogenic induction increases ERK activation, runx2 expression, and nuclear localization, independent of Notch signaling. Finally, we show that Notch and ERK activation are essential for Runx2 DNA binding activity and osteocalcin gene expression in C4-2B cells in response to osteogenic induction. These studies demonstrate that prostate cancer bone metastatic cell lines acquire osteoblastic properties through independent activation of ERK and Notch signaling; presumably, both pathways are activated in the bone microenvironment.     

Stereotactic radiotherapy for bone oligometastases

About 60–90% of cancer patients are estimated to develop bone metastases, particularly in the spine.Bone scintigraphy, computed tomography (CT ) and magnetic resonance imaging (MRI ) are currently used to assess metastatic bone disease; positron emission tomography/computed tomography (PET-CT ) has become more widespread in clinical practice because of its high sensitivity and specificity with about 95% diagnostic accuracy. The most common and well-known radiotracer is 18F-fluorodeoxyglucose (¹⁸FDG); several other PET-radiotracers are currently under investigation for different solid tumors, such as ¹¹C or ¹⁸FDG-choline and prostate specific membrane antigen (PSMA)-PET/CT for prostate cancer. In treatment planning, standard and investigational imaging modalities should be registered with the planning CT so as to best define the bone target volume. For target volume delineation of spine metastases, the International Spine Radiosurgery Consortium (ISRC ) of North American experts provided consensus guidelines. Single fraction stereotactic radiotherapy (SRT ) doses ranged from 12 to 24 Gy; fractionated SRT administered 21–27 Gy in 3 fractions or 20–35 Gy in 5 fractions. After spine SRT, less than 5% of patients experienced grade ≥ 3 acute toxicity. Late toxicity included the extremely rare radiation-induced myelopathy and a 14% risk of de novo vertebral compression fractures.     

Hypermétabolismes médullaires en TEP au 18F-FDG chez les patients atteints de cancer : signification et comparaison à l’IRM médullaire

Diffuse bone marrow uptake of ¹⁸F-FDG-PET in cancer patients raises the problem of differential diagnosis between marrow involvement and stimulated marrow. In this study, we prospectively included, during a 1-year period, all cancer patients referred for initial staging showing an unexplained diffuse bone marrow uptake and explored consecutively by MRI. The abnormalities described on PET and the conclusion reached about disease status of bone marrow (“benign” or “malignant”) were compared with corresponding MRI results, as well as clinical and biological findings pertinent when bone marrow activity is studied, marrow status considered by referring clinicians, and follow-up data. During 1 year, 60 patients had diffuse bone marrow uptake on ¹⁸F-FDG-PET, 26 underwent MRI examination and were finally included in the study. Results of PET and MRI were concordant in 24 cases (six “malignant” and 18 “benign”) and two cases were discordant, judged “malignant” by MRI and “benign”by PET. The outcome after confrontation of MRI and PET, was “malignant”for one patient and “benign” for the other one. The final results, was “malignant” for seven patients and “benign” for 19 patients and this final diagnosis was retained by referring clinicians. Among the 19 patients with diffuse bone marrow uptake considered as benign, seven patients had a pejorative evolution and four of them developed osteomedullary metastases. In cancer patients, ¹⁸F-FDG-PET identify bone marrow diffuse uptake which seems to correspond well to abnormalities assessed on MRI studies. Notably, heterogenous 18F-FDG uptake and/or foci of increased uptake seems significative of marrow involvement. The limited population size and discordant published findings about bone marrow evaluation by ¹⁸F-FDG-PET compared with MRI can not permit to ensure that these imaging modalities or one of these are sufficient to assess bone marrow status without performing bone marrow biopsy. Some patients with unexplained diffuse bone marrow uptake develop disease progression, such observations could be interestingly assessed by further studies.     

Detection of Rib Metastases in Patients with Lung Cancer: A Comparative Study of MRI,CT and Bone Scintigraphy

We retrospectively investigated the imaging findings of bone scintigraphy, chest CT and chest MRI in 55 cases of lung cancer. The sensitivity, specificity and accuracy of the detection of rib metastases were compared between imaging modalities on both a per-lesion and a per-patient basis. On a per-lesion basis, MRI sensitivity and accuracy were significantly higher than that of bone scintigraphy and CT (P<0.05). The sensitivities, specificities, and accuracy levels between CT and bone scintigraphy did not differ on either a per-lesion or per-patient basis (P>0.05). MRI appears to be superior for the detection of ribs metastases in lung cancer.