Repeated quantitative bone scintigraphy in patients with prostatic carcinoma treated with orchiectomy

Bone scintigraphy was performed in 16 men with newly diagnosed prostatic carcinoma before orchiectomy as well as 2 weeks and 2 months after operation. The uptake in the lower thoracic and lumbar vertebrae was registered up to 240 min after injection of ^99mTc-MDP and was then calculated for each patient and vertebra. The relative standard deviation in measured uptake due to measuring technique was estimated to be±7%. In eight patients, who had normal bone scintigraphies before orchiectomy, there were no changes in the uptake values after operation. The remaining eight patients had widespread metastatic involvement prior to treatment. Six of these patients showed a so called flare phenomenon in the abnormal vertebrae which means an initial increase in uptake after operation followed by a decreased uptake in response to therapy. One patient had a continuously increased uptake in all the abnormal vertebrae which correlated well with the clinical progression of the disease, while in another patient both reactions were seen. Thus, repeated quantitative bone scintigraphies using ^99mTc-MDP can be made in a reproducible way and can be a useful tool to follow a patient's response to treatment.     

Relationship between 99Tcm-MDP uptake and bone mineral density in patients with prostatic carcinoma

Seventeen men with prostatic carcinoma were investigated with quantitative bone scintigraphy and quantitative computed X-ray tomography before orchiectomy and up to 6 months after this operation. The uptake of 99Tcm-labelled methylene disphosphonate (99Tcm-MDP) and bone mineral density (BMD) were determined for each vertebra from Th10 to L4. Ten patients had normal scintigrams. No change in MDP uptake or BMD was seen after 6 months in these patients. Of the seven patients with abnormal scintigrams, one patient had a clinical sign of progression with an increase in both MDP uptake and BMD. The remaining six patients showed stable or improved clinical status. For their abnormal vertebrae a decrease in MDP uptake was seen, while BMD varied in different ways after 6 months. For the normal vertebrae in these patients with metastatic involvement, no change in MDP uptake was seen. However, the BMD values showed a decrease, indicating a generalized increase in bone resorption at sites distant from the metastases.     

The usefulness of bone-marrow scintigraphy in the detection of bone metastasis from prostatic cancer

We used a combination of bone and bone-marrow scintigraphy to study 25 patients with prostatic cancer. Of the 18 cases whose ^99mTc-methylene diphosphonate (MDP) bone scans showed hot spots in the lower lumbar region of the spine and/or the pelvic bone, 8 had normal bone-marrow scintigrams. These 8 patients were subsequently shown to have senile, degenerative changes of the spine. On the other hand, in 9 of the 10 patients whose bone-marrow scintigrams showed accumulation defects, follow-up study and characteristic X-ray findings confirmed the presence of metastases. In all 6 cases with extensive bone metastases shown by ^99mTc-MDP bone scintigraphy, ^99mTc-sulphur-colloid bone-marrow scintigraphy showed multiple accumulation defects. In conclusion, bone-marrow scintigraphy was found to be useful in distinguishing metastatic lesions from benign degenerative changes in the cases with suspected bone involvement, as well as in evaluating equivocal lesions in the pelvis.     

Repeated quantitative bone scintigraphy in patients with prostatic carcinoma treated with orchiectomy

Bone scintigraphy was performed in 16 men with newly diagnosed prostatic carcinoma before orchiectomy as well as 2 weeks and 2 months after operation. The uptake in the lower thoracic and lumbar vertebrae was registered up to 240 min after injection of 99mTc-MDP and was then calculated for each patient and vertebra. The relative standard deviation in measured uptake due to measuring technique was estimated to be +/- 7%. In eight patients, who had normal bone scintigraphies before orchiectomy, there were no changes in the uptake values after operation. The remaining eight patients had widespread metastatic involvement prior to treatment. Six of these patients showed a so called "flare phenomenon" in the abnormal vertebrae which means an initial increase in uptake after operation followed by a decreased uptake in response to therapy. One patient had a continuously increased uptake in all the abnormal vertebrae which correlated well with the clinical progression of the disease, while in another patient both reactions were seen. Thus, repeated quantitative bone scintigraphies using 99mTc-MDP can be made in a reproducible way and can be a useful tool to follow a patient's response to treatment.     

Extensive soft-tissue involvement of dermatomyositis detected by whole-body scintigraphy with99mTc-MDP and201Tl-chloride

The authors present a case of extensive soft-tissue radioactivity visualized on both^99mTc-MDP and²⁰¹Tl-chloride scintigrams in a patient with dermatomyositis and colon cancer. Incidentally, diffuse and intense uptake of^99mTc-MDP was observed in the shoulder girdles, anterior chest wall, psoas muscles, both proximal thighs and right lower limb, corresponding to the sites of symptomatic muscles, even though skin lesions were limited and no calcification was detected on radiographs. Moreover,²⁰¹Tl-chloride was also intensely accumulated in nearly the same sites as the symptomatic muscles as shown on the^99mTc-MDP bone scintigrams. Whole-body scintigraphy with^99mTc-MDP and²⁰¹Tl-chloride is a useful tool to detect occult muscle lesions with dystrophic calcification and hyperemia in dermatomyositis.     

A comparison of iodine-123 meta-iodobenzylguanidine scintigraphy and single bone marrow aspiration biopsy in the diagnosis and follow-up of 26 children with neuroblastoma

In staging neuroblastomas, the demonstration of tumoural invasion of the bone marrow is an important criterion with regard to the therapeutic prospects and the prognosis. Iliac crest aspiration sampling has been used routinely for the detection of bone marrow metastases in neuroblastoma. However, due to the limited character of the sampling, it sometimes leads to false-negative results. Another procedure which is used to determine the extent of neuroblastoma is metaiodobenzylguanidine (mIBG) scintigraphy. In order to establish the respective merits of both diagnostic techniques retrospectively, 148 iodine-123 mIBG scans of 26 children with neuroblastoma have been re-evaluated and compared with the results of routine bone marrow samples obtained within a 4-week period before or after scanning. Three types of mIBG uptake in the bone/bone marrow could be differentiated: (1) no visualization of the skeleton; (2) diffuse uptake in the skeleton with or without focally increased uptake, which indicates massive, diffuse bone marrow invasion by the tumour; and (3) focal tracer accumulation in one or several bones. No tracer uptake was observed in the skeleton in 91 scans. In 89 of the 91 the bone marrow biopsy was negative. Twenty-four scans showed diffuse skeletal uptake with or without foci. The bone marrow biopsies were negative for eight of those 24 scans. Hyperactive foci in one or more bones without diffuse tracer accumulation in the skeleton were detected in 33 scans. In only 7 of these 33 scans did bone marrow biopsy specimens from the iliac MDP crest contain neuroblastoma cells. Available technetium-99m methylene diphosphonate (MDP) whole-body scintigrams were also compared with the corresponding mIBG scans. Thirty-eight mIBG scans showed no visualization of the skeleton; ^99mTc-MDP scintigrams were also normal. Seven patients with diffuse mIBG uptake in the skeleton appeared as normal on the ^99mTc-MDP scans. Among 27 cases showing focal mIBG uptake in the skeleton with or without diffuse uptake, only I8 demonstrated a hot spot on the bone scintigram. The results of our study indicate that for the assessment of bone marrow infiltration by neuroblastoma, 1231-mIBG scintigraphy is more sensitive than the conventional cytological examination of bone marrow smears routinely obtained from the iliac crest, has a very high sensitivity in excluding bone marrow invasion, has a high specificity for detecting bone marrow invasion, appears to be able to detect early tumoural deposits in the bone marrow before osseous invasion occurs as shown on the MDP scans and is superior to ^99mTc-MDP bone scan in detecting bone/bone marrow metastases of neuroblastoma. In patients with a positive mIBG scan in the skeleton, bone marrow biopsy will not yield additional information. Correspondence to: K. Osmanagaoglu     

Clinical significance of technetium-99m methylene diphosphonate myocardial uptake: association with carcinoma of the prostate

Benign myocardial uptake of technetium-99m labelled phosphates, not related to cardiac or metabolic disorders, has been documented except in the case of^99mTc-methylene diphosphonate (MDP). The aim of this study was to assess the frequency of myocardial uptake and its possible association with malignant tumours in general and prostatic carcinoma in particular. We reviewed bone scintigrams performed with either^99mTc-hydroxydiphosphonate (HDP) or^99mTc-MDP over a period of more than 2 years for all patients with prostatic carcinoma and a matching group of patients suffering from other malignant and non-malignant disorders. A total of 965 scintigrams of 812 patients (males=559, females=253; age range 50–91 years, average age 69.2 years) were reviewed. Increased myocardial uptake was detected in 19 scintigrams (MDP=13, HDP=6) of 18 patients (17 males, one female). Most of the male patients with increased myocardial uptake had prostatic carcinoma (13/17) and were over 80 years of age (12/17). All patients were free of any cardiac or noncardiac disorder that might account for such uptake. When scintigraphy was repeated in the same patient, the uptake of^99mTc-HDP was more diffuse and of higher grade than that of^99mTc-MDP Benign myocardial uptake of^99mTc-MDP is more common than previously thought. Although uptake of radiophosphates is attributed to asymptomatic atherosclerotic changes associated with old age, a strong association with prostatic carcinoma exists which may indicate variations in the bone: soft tissue affinity of different MDP complexes.     

Uptake and localization of99mTc-methylene diphosphonate in mouse osteosarcoma

The localization of^99mTc-methylene diphosphonate (^99mTc-MDP) in mouse osteosarcoma was studied using a skeletal scintigraphic method and macro- and microautoradiographic methods. On the skeletal scintigraph, the tumor showed a high uptake of^99mTc-DMP and its concentration was about 20 times as high as the value seen in the muscular tissue. The macroautoradiography showed high activity in the tumor bone region and little activity in the nonossified region. On the microautoradiography, the activity of^99mTc-MDP was localized in the mineralized matrix of tumor bone and was almost nil in the nonmineralized matrix (osteoid) and the tumor cells. These findings indicate that the mineralization of the tumor bone matrix plays an important role in^99mTc-MDP uptake in osteosarcoma.     

Detection of vertebral metastases: comparison between MR imaging and bone scintigraphy

In a double-blind, prospective study, the authors analyzed bone scintigrams and magnetic resonance (MR) images of the spine in 71 patients with histologically proved skeletal metastases. Bone scintigrams and MR images were separately reviewed by four independent observers. Bone scintigraphy permitted identification of 499 abnormal vertebrae and MR imaging, 818 abnormal vertebrae. MR imaging depicted additional abnormal vertebrae in 49 patients. The authors conclude that MR imaging is more sensitive than bone scintigraphy in detection of vertebral metastases.     

The clinical reliability of 99mTc-polyphosphate skeletal scintigraphy in the early detection of bone metastases

A comparison between ^99mTc-polyphosphate and pyrophosphate for the early detection of skeletal metastases demonstrated a significant difference between them. Of 71 lesions visualized by polyphosphate scintigrams only 54 were to be found on pyrophosphate scintigrams. The lesions not visualized by pyrophosphate were associated with bone with a high bone-marrow content. It has been suggested that polyphosphate should be the reagent of choice for the detection of skeletal malignancy. In a retrospective study of 118 patients the diagnostic reliability of positive polyphosphate scintigrams was found to be in excess of 90% in patients where skeletal associated pain was the only indication of metastasis.     

The rabbit biodistribution of a therapeutic dose of zoledronic acid labeled with Tc-99m

The aim of the present study was to label a therapeutic dose of zoledronic acid (ZOL) with Tc-99m, evaluate its in vitro stability and compare its biodistribution to ^99mTc-methylene biphosphonate (^99mTc-MDP) in normal rabbits. Preparation of 0.50 mg of ^99mTc-ZOL was carried out by the reduction of ^99mTc-pertechnetate in the presence of stannous chloride. The radiolabeling efficiency was found to be greater than 99%. The labeled complex was stable at least up to 6 h at room temperature determined by paper chromatography. ^99mTc-ZOL and ^99mTc-MDP were administered intravenously to the rabbits for scintigraphic studies. Between ^99mTc-ZOL and ^99mTc-MDP, there were no significant differences in the ratios of femur/BG and lumbar vertebrae/BG, whereas epiphysis/BG and the kidney/BG ratios of ^99mTc-MDP were higher than ^99mTc-ZOL at the static studies.     

Intestinal uptake of <Superscript>99m</Superscript>Tc-MDP: a case report of protein-losing enteropathy correlated with pathology findings from autopsy

We present a case of a 60-year-old man with a history of severe hypoproteinemia and constitutional syndrome, suspected to have protein-losing enteropathy (PLE). Bone scintigraphy (^99mTc-MDP) performed to rule out the presence of bone metastases incidentally showed abnormal uptake in abdominal soft tissue. The patient unexpectedly died of heart failure, and autopsy revealed microscopic alterations consistent with PLE exclusively in the right colon, corresponding to the area of abnormal uptake. Few similar cases have been published, but none of them reported correlative pathological findings affecting the area of abnormal tracer uptake. In this case of PLE, ^99mTc-MDP scintigraphy was a useful imaging method for localizing the site of protein loss, showing a focal area of alteration in the right colon. This finding could also have been of great help in case that surgery had been finally performed to control the protein loss.     

The role of 18F-fluoride PET-CT in the detection of bone metastases in patients with breast, lung and prostate carcinoma: a comparison with FDG PET/CT and 99mTc-MDP bone scan

Objectives

We aimed to compare the role of ¹⁸F-fluoride PET/CT, FDG PET/CT and ^99mTc-MDP bone scans in the detection of bone metastases in patients with lung, breast and prostate carcinoma.

Methods

This was a prospective study including patients for staging (S) and restaging (R). Seventy-two patients (23S, 49R) with infiltrating ductal breast carcinoma, 49 patients (25S, 24R) with prostate adenocarcinoma and 30 patients (17S, 13R) with non-small-cell lung carcinoma (NSCLC), without known bone metastases but with high risk/clinical suspicion for the same, underwent a ^99mTc-MDP bone scan, FDG PET/CT and ¹⁸F-fluoride PET/CT within 2 weeks. All scans were reviewed by two experienced nuclear medicine physicians, and the findings were correlated with MRI/thin-slice CT/skeletal survey. Histological verification was done wherever feasible.

Results

Sensitivity and negative predictive value (NPV) of ¹⁸F-fluoride PET/CT was 100 % in all three malignancies, while that of FDG PET/CT was 79 % and 73 % in NSCLC, 73 % and 80 % in breast cancer and 72 and 65 % in prostate cancer. Specificity and positive predictive value (PPV) of FDG PET/CT were 100 % in NSCLC and prostate and 97 % and 96 % in breast cancer. As compared to the ^99mTc-MDP bone scan, all parameters were superior for ¹⁸F-fluoride PET/CT in prostate and breast cancer, but sensitivity and NPV were equal in NSCLC. The MDP bone scan had superior sensitivity and NPV compared to FDG PET/CT but had low specificity and PPV.

Conclusion

To rule out bone metastases in cases where there is a high index of suspicion, ¹⁸F-fluoride PET/CT is the most reliable investigation. ¹⁸F-fluoride PET/CT has the potential to replace the ^99mTc-MDP bone scan for the detection of bone metastases.     

The complementary role of sequential 99mTc-MDP and 67Ga-citrate scanning in the diagnosis and follow-up of neuroblastoma

Fourteen children with histopathologically confirmed neuroblastoma underwent 38 studies using ^99mTc-methylene-diphosphonate (MDP) and galliumcitrate Ga67 whole-body scintigraphy during various stages of the disease. Ten patients (71%) showed ^99mTc-MDP accumulation in the primary tumoral site, whereas 11 patients (78.6%) showed ⁶⁷Ga concentration. In 12 patients (86%), at least one of these two radiopharmaceuticals concentrated in the primary tumor. Nine patients had osseous or extraosseous metastases. All of these metastases (100%) were positive on ^99mTc-MDP sctintigraphy. No ⁶⁷Ga-citrate uptake was demonstrable in osseous metastases; only one extraosseous lung metastasis concentrated this radiopharmaceutical. ⁶⁷Ga-citrate was superior to ^99mTc-MDP with regard to accurately demonstrating the extent of primary tumors. Only ^99mTc-MDP indicated the relationship of the tumor to the kidneys and neighbouring osseous structures, prividing early screening of kidney compression and possible damage caused by the tumor. From these results, we found these two methods to be complementary for the diagnosis and follow-up of neuroblastoma; their combined use resulted in high diagnostic accuracy and a considerable gain of information. We therefore recommend sequential ^99mTc-MDP and ⁶⁷Ga-citrate scans for the diagnosis and evaluation of the primary tumor; periodic ^99mTc-MDP wholebody scans should be used in the follow-up of treatment, and for discovering disease exacerbations and metastases.Presented in part in the European Congress of Nuclear Medicine, London, England, September 1985     

Tc-citrate versus Ga-citrate for the scintigraphic visualization of inflammatory lesions

Citric acid was labeled with ^99mTc with an efficiency of > 99%. The biodistribution of ^99mTc-citrate was studied in mice with turpentine-induced abscesses in comparison to ⁶⁷Ga-citrate. The max. concentration ratios were 4.61 ± 1.92 (3 h) for ^99mTc-citrate and 4.76 ± 2.04 (4h) for ⁶⁷Ga-citrate. Arthritis was induced in 10 rabbits by intra-articular injection of ovalbumin Scintigrams obtained 4 days later and at 3 h post-injection of ^99mTc-citrate showed increased activity involving the synovium. The max. knee ratio was 3.19 ± 1.29 (3 h) and 6.47 ± 3.71 (24 h) for ^99mTc- and ⁶⁷Ga-citrate, respectively. The blood clearance curve of ^99mTc-citrate in rabbits was biexponential with a fast ( ) and a slow ( ) component, compared to mono-exponential clearance of ⁶⁷Ga-citrate ( ). In 10 patients with rheumatoid arthritis whole-body scintigrams and spot images of involved joints indicated localization of the tracer in inflamed tissues. The mean target-to-soft tissue ratios were 3.04 ± 0.81 and 4.95 ± 2.56 for ^99mTc-citrate and ^99mTc-MDP, respectively. Renal clearance of radioactivity was evident from the scintigrams. Our results demonstrated that ^99mTc-citrate is effective as a radiopharmaceutical for the visualization of inflammatory lesions and may be preferred to ⁶⁷Ga-citrate due to the ideal physical characteristics of the radionuclide, easy preparation, low cost, early accumulation and the preference for the renal route of excretion.     

Deconvolution analysis of 99mTc-methylene diphosphonate kinetics in metabolic bone disease

The kinetics of ^99mTc-methylene diphosphonate (MDP) and ⁴⁷Ca were studied in three patients with osteoporosis, three patients with hyperparathyroidism, and two patients with osteomalacia. The activities of ^99mTc-MDP were recorded in the lumbar spine, paravertebral soft tissues, and in venous blood samples for 1 h after injection. The results were submitted to deconvolution analysis to determine regional bone accumulation rates. ⁴⁷Ca kinetics were analysed by a linear two-compartment model quantitating short-term mineral exchange, exchangeable bone calcium, and calcium accretion. The ^99mTc-MDP accumulation rates were small in osteoporosis, greater in hyperparathyroidism, and greatest in osteomalacia. No correlations were obtained between ^99mTc-MDP bone accumulation rates and the results of ⁴⁷Ca kinetics. However, there was a significant relationship between the level of serum alkaline phosphatase and bone accumulation rates (R=0.71, P<0.025). As a result deconvolution analysis of regional ^99mTc-MDP kinetics in dynamic bone scans might be useful to quantitate osseous tracer accumulation in metabolic bone disease. The lack of correlation between the results of ^99mTc-MDP kinetics and ⁴⁷Ca kinetics might suggest a preferential binding of ^99mTc-MDP to the organic matrix of the bone, as has been suggested by other authors on the basis of experimental and clinical investigations.     

Pitfalls in the diagnosis of neuroblastoma by 99mTc-MDP scintigraphy: A case report

A routine bone scan was performed on an infant presenting with abdominal mass. Initially, the stasis of activity in the right ureter, which was compressed by a large abdominal meningocoele, was mistaken for activity in a neuroblastoma. A subsequent kidney scintigram led to the correct interpretation. The misinterpretation of abdominal ^99mTc-MDP accumulation can be prevented by the correlation of bone and kidney scintigrams. In this way, the correct site of the radiopharmaceutical concentration can be assessed, and the damage caused by any kind of abdominal mass to the compressed urinary tract and kidney can be assessed.     

99mTc-MDP retention in osteoporosis: Relationship to other indices of bone cell activity and response to calcium and vitamin D therapy

Serum calcium, albumin, phosphorus, and alkaline phosphatase, urinary creatinine and retention of ^99mTc-methylene bisphosphonate (^99mTc-MDP) were measured in 61 subjects with osteoporosis and the values compared with those obtained in normal subjects. ^99mTc-MDP retention was inversely related with urinary creatinine output in normal subjects. In osteoporotic subjects urinary creatinine output was lower and ^99mTc-MDP retention higher even when urinary creatinine output was taken into account. Other measurements were similar. In 21 subjects these measurements together with urinary hydroxyproline were performed before and after treatment with calcium and vitamin D. ^99mTc-MDP and alkaline phosphatase fell; urinary hydroxyproline was unchanged. A single 24 h urine measurement after ^99mTc-MDP injection is a valuable method of predicting whether calcium and vitamin D therapy will be useful in a particular case of osteoporosis.     

Dual-phase 99mTc-MIBI scintigraphy with delayed neck and thorax SPECT/CT and bone scintigraphy in patients with primary hyperparathyroidism: correlation with clinical or pathological variables

Purpose

The purpose of this study was to assess the relationship between ^99mTc-MIBI and ^99mTc-MDP bone scintigraphy and clinical or pathological variables, including preoperative serum PTH levels and tumor diameter, in patients with newly diagnosed PHPT.

Methods

Dual-phase ^99mTc-MIBI planar scintigraphy was performed in 244 patients with PHPT. Of these patients, 155 underwent ^99mTc-MDP bone scintigraphy to detect bone changes before parathyroidectomy. Factors influencing ^99mTc-MIBI scintigraphy and ^99mTc-MDP bone scintigraphy detection rate were assessed using univariate and multivariate logistic regression analysis; optimal cutoff values for predicting positive ^99mTc-MIBI and ^99mTc-MDP bone scintigraphy were evaluated using ROC analysis.

Results

Among 244 patients, 174 (71.31 %) patients with 181 foci had a positive ^99mTc-MIBI planar scintigraphy; delayed neck and thorax SPECT/CT could identify and locate the ^99mTc-MIBI lesions but could not find more lesions than planar scintigraphy. 70 (28.69 %) patients had a negative ^99mTc-MIBI planar scintigraphy. Tumor diameter, serum PTH level and symptoms were statistically significant predictive factors in predicting positive ^9mTc-MIBI scintigraphy both univariate and multivariate logistic regression analyses. The optimal thresholds for tumor diameter and serum PTH by ROC analysis were 1.03 cm and 127.60 ng/L, respectively. Among 155 patients with bone scintigraphy, ^99mTc-MDP bone scintigraphy showed positive finding in 80 (51.61 %) patients and negative finding in 75 patients. Univariate logistic regression analysis showed that patient age, sex, tumor diameter and PTH level (≥150 ng/L) were statistically significant in predicting positive ^99mTc-MDP bone scintigraphy. Multivariate logistic regression analysis showed both tumor diameter and PTH ≥ 150 ng/L were statistically significant in predicting positive ^99mTc-MDP bone scintigraphy. The optimal thresholds for tumor diameter and serum PTH by ROC analysis were 1.96 cm and 163.85 ng/L, respectively.

Conclusions

The utility of delayed neck and thorax SPECT/CT over dual-phase ^99mTc-MIBI planar scintigraphy is that it can identify and locate a parathyroid tumor in about more than 70 % of patients in PHPT and provide the assistance for surgical planning. These studies also suggest that ^99mTc-MIBI scintigraphy and ^99mTc-MDP bone scintigraphy are closely correlated with tumor diameter and PTH; which may show negative results when tumor diameter is small and serum PTH level is low.     

Preparation and preclinical pharmacological study on a novel bone imaging agent 99mTc-EMIDP

A novel zoledronic acid (ZL) derivative, 1-hydroxy-2-(2-ethyl-4-methyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (EMIDP), was prepared and labeled with ^99mTc successfully in a high labeling yield and good stability in vitro. The preclinical pharmacological properties of ^99mTc-EMIDP were investigated and compared with ^99mTc-MDP and ^99mTc-ZL. The studies of biodistribution in mice and SPECT bone imaging of the rabbit suggest that ^99mTc-EMIDP has highly selective uptake in the skeletal system and rapid clearance in the soft tissues. The present findings indicate that ^99mTc-EMIDP holds great potential for bone scintigraphy.