Comparison of 18F-fluoride PET/CT, 18F-FDG PET/CT and bone scintigraphy (planar and SPECT) in detection of bone metastases of differentiated thyroid cancer: a pilot study

Objective:

We compared the efficacies of ¹⁸F-fluoride positron emission tomography (¹⁸F-fluoride PET)/CT, ¹⁸F-fludeoxyglucose PET (¹⁸F-FDG PET)/CT, and ^99mTc bone scintigraphy [planar and single photon emission CT (SPECT)] for the detection of bone metastases in patients with differentiated thyroid carcinoma (DTC).

Methods:

We examined 11 patients (8 females and 3 males; mean age ± standard deviation, 61.9 ± 8.7 years) with DTC who had been suspected of having bone metastases after total thyroidectomy and were hospitalized to be given ¹³¹I therapy. Bone metastases were verified either when positive findings were obtained on both ¹³¹I scintigraphy and CT or when MRI findings were positive if MRI was performed.

Results:

Metastases were confirmed in 24 (13.6%) of 176 bone segments in 9 (81.8%) of the 11 patients. The sensitivities of ¹⁸F-fluoride PET/CT and ^99mTc bone scintigraphy (SPECT) were significantly higher than those of ¹⁸F-FDG PET/CT and ^99mTc bone scintigraphy (planar) (p < 0.05). The accuracies of ¹⁸F-fluoride PET/CT and ^99mTc bone scintigraphy (SPECT) were significantly higher than that of ^99mTc bone scintigraphy (planar) (p < 0.05).

Conclusion:

The sensitivity and accuracy of ¹⁸F-fluoride PET/CT for the detection of bone metastases of DTC are significantly higher than those of ^99mTc bone scintigraphy (planar). However, the sensitivity and accuracy of ^99mTc bone scintigraphy (planar) are improved near to those of ¹⁸F-fluoride PET/CT when SPECT is added to a planar scan. The sensitivity of ¹⁸F-FDG PET/CT is significantly lower than that of ¹⁸F-fluoride PET/CT or ^99mTc bone scintigraphy (SPECT).

Advances in knowledge:

This article has demonstrated first the high efficacy of ¹⁸F-fluoride PET/CT for the detection of bone metastases of DTC.Differentiated thyroid carcinoma (DTC) shows a relatively good prognosis compared with carcinomas of other organs, and the 10-year survival rate of DTC is >80% because of treatments such as total thyroidectomy and ablation of remnants with radioiodine.¹ However, metastases of DTC develop in 7–23% of patients; the distant metastases occur commonly in the lungs, bones and brain, and the bones are the second most common site of metastases of DTC.² Bone scintigraphy using ^99mTc-labelled phosphate compounds [^99mTc-methylene diphosphonate (^99mTc-MDP) or ^99mTc-hydroxymethylene diphosphonate (^99mTc-HMDP)] has been widely used for detecting and evaluating bone metastases of various kinds of carcinomas because of its overall high sensitivity and the easy evaluation of the entire skeleton.³ However, there were often false-positive cases in ^99mTc bone scintigraphy, because degenerative or inflammatory foci were often confused with metastatic lesions. The addition of single photon emission CT (SPECT) to planar acquisition of ^99mTc bone scintigraphy has been shown to exhibit a beneficial effect on the detection and evaluation of bone metastases.^4–6 Skeletal imaging by ¹⁸F-fludeoxyglucose positron emission tomography (¹⁸F-FDG PET)/CT has been shown to be useful in the detection of bone metastases of various carcinomas including DTC.⁷Previously, we compared the efficacies of ¹⁸F-FDG PET and planar ^99mTc bone scintigraphy for the detection of bone metastases in patients with DTC.⁸ We found that the specificity and the overall accuracy of ¹⁸F-FDG PET for the detection of bone metastases in patients with DTC were higher than those of planar ^99mTc bone scintigraphy, whereas the difference in the sensitivity of both examinations was not statistically significant, and concluded that ¹⁸F-FDG PET is superior to planar ^99mTc bone scintigraphy because of its lower incidence of false-positive results in the detection of bone metastases of DTC.⁸¹⁸F-fluoride is a positron-emitting bone-seeking radiotracer, which has a similar uptake mechanism to ^99mTc-MDP and ^99mTc-HMDP. As the availability of PET systems was increasing, ¹⁸F-fluoride has been used for skeletal PET imaging since 1990s. PET or PET/CT with ¹⁸F-fluoride have been shown to be more sensitive than planar ^99mTc bone scintigraphy for the detection of bone metastases of lung,⁹ breast,^10,11 hepatocellular,¹² prostate,^11,13,14 colon and bladder¹¹ cancers. However, to the best of our knowledge, there have been no systematic comparative studies on the efficacies of ¹⁸F-fluoride PET/CT, ¹⁸F-FDG PET/CT and ^99mTc bone scintigraphy (planar and SPECT) for the detection of bone metastases of DTC. This study was conducted to compare ¹⁸F-fluoride PET/CT, ¹⁸F-FDG PET/CT and ^99mTc bone scintigraphy (planar and SPECT) in the detection of bone metastases of DTC.     

Comparison of whole-body <Superscript>18</Superscript>F-FDG PET, <Superscript>99m</Superscript>Tc-MIBI SPET,and post-therapeutic <Superscript>131</Superscript>I-Na scintigraphy in the detection of metastatic thyroid cancer

The usefulness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid cancer (DTC) has been demonstrated by many investigators, but in only a small number of studies have FDG-PET images been compared with those obtained using other non-iodine tumour-seeking radiopharmaceuticals. In most of the studies, planar imaging was performed for comparison using thallium-201 chloride or technetium-99m 2-methoxyisobutylisonitrile (^99mTc-MIBI). Furthermore, FDG-PET studies were not always performed in the hypothyroid state with increased levels of thyroid stimulating hormone (TSH), which are known to increase FDG uptake by DTC. The aim of this study was to compare the ability of FDG-PET to detect metastatic DTC with that of ^99mTc-MIBI whole-body single-photon emission tomography (SPET) and post-therapeutic iodine-131 scintigraphy, evaluated under TSH stimulation. Nineteen patients (8 men, 11 women; age range, 38–72 years, mean 60 years; 17 thyroidectomised and 2 inoperable patients following ¹³¹I ablation of the remaining thyroid tissue; 16 papillary and 3 follicular carcinomas) with metastatic DTC underwent FDG-PET whole-body scan (WBS) and ^99mTc-MIBI SPET WBS at an interval of less than 1 week, followed by ¹³¹I therapy. The SPET images were reconstructed using the maximum likelihood expectation maximisation (ML-EM) method. All patients were hypothyroid at the time of each scan. ¹³¹I WBS was performed 3–5 days after oral administration of the therapeutic dose. A total of 32 lesions [10 lymph node (LN), 15 lung, 6 bone, 1 muscle] were diagnosed as metastases, as confirmed by histopathology and/or other imaging modalities (X-ray, US, CT, MRI, bone, ²⁰¹Tl and ¹³¹I scans). FDG-PET, ^99mTc-MIBI SPET and post-therapeutic ¹³¹I scintigraphy respectively revealed a total of 26 (81.3%), 20 (62.5%) and 22 (68.8%) lesions. These techniques respectively demonstrated nine (90.0%), eight (80.0%) and six (60.0%) LN metastases, and eleven (73.3%), seven (46.7%) and ten (66.7%) lung metastases. They each demonstrated five of the six bone metastases (83.3%). FDG-PET and ^99mTc-MIBI SPET were positive in 17 (78.3%) and 14 (63.6%) of the 22 ¹³¹I-positive lesions, respectively, and also in nine (90.0%) and six (60.0%) of the ten ¹³¹I-negative lesions, respectively. Three of the five ¹³¹I-positive and FDG-PET-negative lesions were miliary type lung metastases with a maximal nodular diameter of less than 10 mm. Comparison of FDG-PET with ^99mTc-MIBI SPET revealed concordant results in 24 lesions, and discordant results in eight lesions (seven with positive FDG-PET alone and one with positive ^99mTc-MIBI SPET alone). In conclusion: (a) even using whole-body SPET, FDG PET is superior to ^99mTc-MIBI in terms of ability to detect metastases of DTC; (b) the higher sensitivity of FDG-PET compared with the previous studies could partly be due to increased serum TSH.     

Intense bone imaging agent uptake in the soft tissues of the lower legs and feet relating to ischemia and cold exposure

We present a patient with diffuse and intense uptake in the soft tissues of both lower legs and feet seen on ^99mTc-HMDP bone scintigraphy. This finding presumably resulted from compromised blood supply to the lower legs plus a cold environment. The extraosseous bone imaging agent localization was presumably related to an existing ischemic condition that was exacerbated by cold. Differential diagnosis of the scan pattern should be differentiated from the artifact of socks contaminated by radioactive urine.     

Somatostatin receptor scintigraphy using <Superscript>99m</Superscript>Tc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma

Purpose Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue ^99mTc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Methods Forty-five patients with MTC, aged 14–83 years, were investigated. Scintigraphy using ^99mTc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, ^99mTc(V)-DMSA, ¹³¹I-MIBG, ^99mTc-MDP, ¹¹¹In-DTPA-octreotide and ¹⁸F-FDG-PET) and compared with ^99mTc-EDDA/HYNIC-TOC. Results In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using ^99mTc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. Conclusion ^99mTc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.     

<Superscript>99m</Superscript>Tc-depreotide scintigraphy of bone lesions in patients with lung cancer

Purpose Scintigraphy with ^99mTc-depreotide, a somatostatin analogue–technetium ligand, has been used for evaluation of various malignant neoplasms, including lung cancer. The diagnosis of bone metastases in patients with lung cancer is not always definitive with current imaging methods. Visualisation of somatostatin receptors (SSTRs) in bone lesions, when the primary tumour exhibits such receptors, could be helpful in characterising them as metastatic. The aim of this study was to assess the value of ^99mTc-depreotide in differentiating between benign and malignant bone lesions in patients with lung cancer.Methods The study population comprised 20 patients (17 males and three females, mean age 63 years) with proven lung cancer in whom bone lesions had been detected by conventional imaging methods. All patients underwent ^99mTc-hydroxydiethylene diphosphonate and ^99mTc-depreotide scintigraphy within 2 weeks. Bone lesions were classified as benign or malignant on the basis of clinical, imaging and/or histological criteria.Results ^99mTc-depreotide uptake in the primary tumour was seen in 19 of the 20 patients. Conventional imaging methods detected 55 bone lesions, 31 of which were classified as malignant. Twenty-eight (90%) of these lesions showed ^99mTc-depreotide uptake, suggesting bone metastases, while three did not. Twenty-four bone lesions were classified as benign by conventional imaging methods, and none of them showed ^99mTc-depreotide uptake. In addition, ^99mTc-depreotide demonstrated extra-osseous lesions in six patients.Conclusion In patients with lung cancer and bone lesions, ^99mTc-depreotide scintigraphy uptake in the bone lesions supports the diagnosis of malignancy, in particular if the primary lung tumour also exhibits SSTRs. Furthermore, whole-body ^99mTc-depreotide scintigraphy may disclose extra-osseous disease.     

Indium-111 octreotide scintigraphy for the detection of non-functioning metastases from differentiated thyroid cancer: diagnostic and prognostic value

In this prospective study, we evaluated the diagnostic and prognostic value of ¹¹¹In-octreotide scintigraphy (SRS) in papillary and follicular thyroid carcinoma (DTC) with increasing thyroglobulin (Tg) levels but no response to treatment with ¹³¹I. Twenty-three consecutive patients (13 female, 10 male; mean age 55 years, range 13–81 years) with progressive DTC were selected for the study. All patients had non-functioning metastases, defined by no or slight uptake of ¹³¹I in metastases. Diagnosis of tumour progression was based on rising Tg levels during follow-up and was confirmed by radiological examination. Uptake on SRS was scored from 0 to 4. Data on initial tumour stage, histology, age, gender, Tg values, TSH levels, ¹³¹I treatment doses, intervals and survival were gathered. Seven patients died during follow-up. The overall sensitivity for the detection of metastases was 74%. The sensitivity was better in patients in whom ¹³¹I whole-body scintigraphy did not show any abnormal uptake (82%; 14/17) than in patients with faint ¹³¹I uptake (50%; 3/6). The 10-year survival rate was significantly different between patients with an uptake score of 0 or 1 (100%) and those with an uptake score of 2, 3 or 4 (33%) (P=0.001). Gender, log Tg and uptake on SRS significantly correlated with survival, but in stepwise analysis, ¹¹¹In-octreotide uptake was selected as the most prognostic independent variable (hazard rate 6.25, P=0.006). We conclude that ¹¹¹In-octreotide scintigraphy is a valuable clinical tool for the detection of non-functioning DTC metastases. The uptake seems to correlate with prognosis and survival.     

A patient with cardiac amyloidosis presenting a rapid increase in technetium-99m-hydroxymethylene diphosphonate accumulation

We assessed the changes in cardiac condition in a patient with cardiac amyloidosis, by means of dual nuclei single photon emission computed tomographic (SPECT) images with technetium-99m-hydroxymethylene diphosphonate (^99mTc-HMDP) and thallium-201 (²⁰¹Tl). Dual SPECT showed a marked increase in myocardial^99mTc-HMDP accumulation along with deterioration of symptoms and signs, while²⁰¹Tl scintigraphy remained almost unchanges.     

Comparison of 18F-FDG PET and bone scintigraphy in detection of bone metastases of thyroid cancer.

We compared the efficacies of (18)F-FDG PET and (99m)Tc-bone scintigraphy for the detection of bone metastases in patients with differentiated thyroid carcinoma (DTC). METHODS: We examined 47 patients (32 women, 15 men; mean age +/- SD, 57.0 +/- 10.7 y) with DTC who had undergone total thyroidectomy and were hospitalized to be given (131)I therapy. All patients underwent both whole-body (18)F-FDG PET and (99m)Tc-bone scintigraphy. The skeletal system was classified into 11 anatomic segments and assessed for the presence of bone metastases. Bone metastases were verified either when positive findings were obtained on >2 imaging modalities--(201)Tl scintigraphy, (131)I scintigraphy, and CT--or when MRI findings were positive if vertebral MRI was performed. RESULTS: Bone metastases were confirmed in 59 of 517 (11%) segments in 18 (38%) of the 47 study patients. The sensitivities (visualization rate) for bone metastases on a segment basis using (18)F-FDG PET and (99m)Tc-bone scintigraphy were 50 of 59 (84.7%) and 46 of 59 (78.0%), respectively; the difference between these values was not statistically significant. There were only 2 (0.4%) false-positive cases in a total of 451 bone segments without bone metastases when examined by (18)F-FDG PET, whereas 39 (8.6%) were false-positive when examined by (99m)Tc-bone scintigraphy. Therefore, the specificities of (18)F-FDG PET and (99m)Tc-bone scintigraphy were 449 of 451 (99.6%) and 412 of 451 (91.4%), respectively; the difference between these values was statistically significant (P < 0.001). The overall accuracies of (18)F-FDG PET and (99m)Tc-bone scintigraphy were 499 of 510 (97.8%) and 458 of 510 (89.8%), respectively; the difference between these was also statistically significant (P < 0.001). CONCLUSION: The specificity and the overall accuracy of (18)F-FDG PET for the diagnosis of bone metastases in patients with DTC are higher than those of (99m)Tc-bone scintigraphy, whereas the difference in the sensitivities of both modalities is not statistically significant. In comparison with (99m)Tc-bone scintigraphy, (18)F-FDG PET is superior because of its lower incidence of false-positive results in the detection of bone metastases of DTC.     

Report of a nationwide survey on actual administered radioactivities of radiopharmaceuticals for diagnostic reference levels in Japan

Objective

The optimization of medical exposure is one of the major issues regarding radiation protection in the world, and The International Committee of Radiological Protection and the International Atomic Energy Agency recommend establishing diagnostic reference levels (DRLs) as tools for dose optimization. Therefore, the development of DRLs based on the latest survey has been required for nuclear medicine-related societies and organizations. This prompted us to conduct a nationwide survey on the actual administered radioactivity to adults for the purpose of developing DRLs in nuclear medicine.

Methods

A nationwide survey was conducted from November 25, 2014 to January 16, 2015. The questionnaire was sent to all of the 1249 nuclear medicine facilities in Japan, and the responses were collected on a website using an answered form.

Results

Responses were obtained from 516 facilities, for a response rate of 41 %. 75th percentile of ^99mTc-MDP and ^99mTc-HMDP: bone scintigraphy, ^99mTc-HM-PAO, ^99mTc-ECD and ¹²³I-IMP: cerebral blood flow scintigraphy, ^99mTc-Tetrofosmin, ^99mTc-MIBI and ²⁰¹Tl-Cl; myocardial perfusion scintigraphy and ¹⁸F-FDG: oncology PET (in-house-produced or delivery) in representative diagnostic nuclear medicine scans were 932, 937, 763, 775, 200, 831, 818, 180, 235 and 252, respectively. More than 90 % of the facilities were within the range of 50 % from the median of these survey results in representative diagnostic nuclear medicine facilities in Japan. Responses of the administered radioactivities recommended by the package insert, texts and guidelines such as 740 MBq (^99mTc-MDP and ^99mTc-HMDP: bone scintigraphy), 740 MBq (^99mTc-ECD and ^99mTc-HM-PAO: cerebral blood flow scintigraphy) and 740 MBq (^99mTc-Tetrofosmin and ^99mTc-MIBI: myocardial perfusion scintigraphy), etc. were numerous. The administered activity of many radiopharmaceuticals of bone scintigraphy (^99mTc-MDP and ^99mTc-HMDP), cerebral blood flow scintigraphy (^99mTc-HM-PAO) and myocardial perfusion scintigraphy (^99mTc-Tetrofosmin and ^99mTc-MIBI), etc. were within the range of the EU DRLs and almost none of the administered radioactivity in Japan exceeded the upper limit of SNMMI standard administered radioactivity.

Conclusions

This survey indicated that the administered radioactivity in diagnostic nuclear medicine in Japan had been in the convergence zone and nuclear medicine facilities in Japan show a strong tendency to adhere to the texts and guidelines. Furthermore, the administered radioactivities in Japan were within the range of variation of the EU and the SNMMI administered radioactivities.

     

The role of single-photon emission computed tomography/computed tomography for precise localization of metastases in patients with differentiated thyroid cancer

PurposeIt is very important in the management of patients with differentiated thyroid cancer (DTC) to precisely localize the foci of I-131 uptake, but it is difficult because of a lack of anatomic landmarks. The purpose of this study was to investigate the added value of I-131 single-photon emission computed tomography (SPECT)/computed tomography (CT) fusion imaging using a hybrid system in patients with DTC.MethodsNinety-four patients with DTC underwent I-131 SPECT/CT using a hybrid tomography consisting of a dual-head variable-angle gamma camera and a low-dose X-ray tube. Results were compared with I-131 whole-body scan (WBS). SPECT/CT was performed 5–7 days after administration of a therapeutic dose of I-131. Fusion images were constructed by combining the digital CT and SPECT images on a computer workstation.ResultsCompared with I-131 WBS, SPECT/CT imaging had improved the precise localization in 21% (20/94) of patients. In addition, SPECT/CT provided additional clinical data in 12 of the patients examined (12/94) and also caused physicians to reconsider the ¹³¹I therapeutic approach in 22 patients.ConclusionThe results of the current study indicate that the addition of I-131 SPECT/CT to WBS can improve the localization of metastases in patients with DTC. It may also detect metastases missed by WBS and adjust the therapy plan.     

Ectopic accumulation of99mTc-HMDP in primary lung cancer in comparison with CT findings

The purpose of this study was to evaluate the frequency and the extent of extraosseous^99mTc-HMDP accumulation in 412 patients with primary lung cancer. CT scanning was also performed and we compared the extraosseous uptake by lung cancer with the internal structure of the tumor on CT scans. The extent of ectopic^99mTc-HMDP accumulation was classified as low, moderate or high. CT scans were used to evaluate the size and internal structure of the tumor, including calcification and necrosis. Ectopic^99mTc-HMDP accumulation in primary lung cancer was found in 32 patients (7.7%), and included 2 cases (0.5%) of high uptake, 8 cases (1.9%) of moderate uptake, and 22 cases (5%) of low uptake. No difference in uptake was observed among the histological types, but a relationship between tumor size and^99mTc-HMDP extraosseous accumulation was observed. CT scans of the 32 tumors exhibiting ectopic^99mTc-HMDP accumulation revealed 5 cases of calcification in the tumor and 18 cases of tumor necrosis. The factors promoting ectopic^99mTc-HMDP accumulation were considered to be tumor size and calcification or necrotic change. In patients with neither calcification nor necrosis, other factors such as increased calcium metabolism and altered vascular permeability may be involved.     

Relationship between skeletal uptake of99mTc-HMDP and bone mineral density in elderly women

The relationship between bone mineral density in elderly women and the pattern of skeletal uptake of^99mTc-HMDP, especially in regard to skull uptake, was investigated. The whole-body skeletal uptake (WBSU) and whole-body skeletal tracer distribution patterns were studied in 86 disease-free women on bone scintigraphy with^99mTc-hydroxy-methylene-diphosphonate (HMDP). Bone scans were quantified by setting regions of interest (ROI) and bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry in all patients. WBSU and the skeletal distribution pattern were compared with bone mineral densities of the entire skeleton as well as selected regions. WBSU was high in the elderly and negatively correlated with regional bone mineral densities (r = ?0.403 to ?0.534). Among the regions, uptake by the skull increased with age more than in other regions in women and had the highest negative correlation with the bone mineral density. The skull uptake correlated negatively with total body BMD (r = ?0.583) and with lumbar BMD (r = ?0.561, p< 0.0001). Our results show that increased radionuclide uptake in bone scintigraphy, especially skull uptake was associated with decreased bone mineral density in elderly women, so that, increased skull uptake in elderly women would be a scintigraphic sign of post-menopausal or senile osteopenia.     

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     

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the planning of therapy and follow-up of patients with differentiated thyroid carcinoma after surgery

The aim of this study was to investigate the possible role of technetium-99m methoxyisobutylisonitrile (MIBI) scan in planning post-surgical therapy and follow-up in patients with differentiated thyroid carcinoma (DTC). Four groups of DTC patients were considered: Group 1 comprised 122 patients with high serum thyroglobulin (s-Tg) levels and negative high-dose iodine-131 scan during follow-up who had previously undergone total thyroidectomy and ¹³¹I treatment. Group 2 consisted of 27 patients who had previously undergone total thyroidectomy and ¹³¹I treatment but were now considered disease-free; this group was considered as controls. Group 3 comprised 49 patients studied after total thyroidectomy but prior to ¹³¹I scan. Finally, group 4 consisted of 21 patients who had previously undergone partial thyroidectomy alone. MIBI scan, neck ultrasonography (US), and s-Tg measurements during suppressive hormonal therapy (SHT) were obtained in all patients. Neck and chest computed tomography (CT) or magnetic resonance imaging (MRI) was also performed in group 1 patients. In group 1, MIBI scan and US were very sensitive in detecting cervical lymph node metastases (93.54% and 89.24%, respectively). Furthermore, MIBI scan and US played a complementary role in several patients, yielding a global sensitivity of 97.84%. In contrast, CT/MRI sensitivity for cervical lymph node metastases was very low (43.01%). MIBI scan also showed a higher sensitivity than CT/MRI in detecting mediastinal lymph node metastases (100% vs 57.89%). Regarding distant metastases, MIBI scan provided results similar to those of conventional imaging (CT, MRI, ^99mTc-methylene diphosphonate bone scan). In group 2, no false-positive cases were observed with MIBI scan (100% specificity). In group 3, MIBI scan correctly identified all the ¹³¹I-positive metastatic foci, except in two patients with micronodular pulmonary metastases that were visualised with ¹³¹I scan. In contrast, both MIBI scan and US showed low sensitivity (46.15% and 61.53%, respectively) compared with ¹³¹I scan in detecting thyroid remnants. s-Tg was increased in all patients with distant metastases but only in 56% of those with lymph node metastases. Furthermore, s-Tg was increased in 21.42% of patients with thyroid remnants alone (false-positive results). In group 4, MIBI scan was the only examination capable of detecting at an early stage a mediastinal lymph node metastasis in one patient. We conclude that the integrated MIBI scan/neck US protocol: (a) can be proposed as a first-line diagnostic procedure in the follow-up of DTC patients with high s-Tg levels and negative high-dose ¹³¹I scan, and (b) may be helpful in the follow-up of DTC patients who undergo partial thyroidectomy alone. Moreover, the combined MIBI scan/neck US/s-Tg protocol appears to be highly sensitive in identifying patients with metastatic disease after total thyroidectomy and prior to ¹³¹I scan; consequently, it may play a prognostic role in distinguishing high-risk from low-risk DTC patients. However, due to the low sensitivity of MIBI scan and neck US in detecting thyroid remnants, this diagnostic approach cannot be used as a predictor of ¹³¹I scan results. Lastly, because of the high sensitivity of MIBI scan and neck US in revealing both functioning and non-functioning metastases, this integrated protocol might be helpful in the follow-up of high-risk DTC patients, particularly for the early detection of lymph node metastases in patients with undetectable s-Tg during SHT. Received 21 October and in revised form 20 December 1999     

Utility of 99mTc-labelled antimicrobial peptide ubiquicidin (29-41) in the diagnosis of diabetic foot infection

Purpose

Detection of osteomyelitis beneath a diabetic foot ulcer is imperative for proper management; however, accurate and noninvasive diagnosis of osteomyelitis remains a challenge. Ubiquicidin 29-41 (UBI 29-41) is a synthetic antimicrobial peptide fragment reported to be highly infection-specific. ^99mTc-UBI 29-41 has recently been reported to be a promising radiotracer for infection imaging. The aim of this prospective study was to evaluate the utility of ^99mTc-UBI 29-41 scintigraphy in diabetic patients with suspected osteomyelitis of the foot.

Methods

Included in the study were 65 patients with type 2 diabetes mellitus and foot ulcer and with clinical suspicion of osteomyelitis . Each patient had a three-phase bone scan and a ^99mTc-UBI scan at 30 and 60 min after injection. The scan was considered to be consistent with osteomyelitis when the ^99mTc-UBI 29-41 uptake was concordant with the ^99mTc-MDP uptake. It was considered negative for osteomyelitis if there was no uptake of ^99mTc-UBI 29-41 or if ^99mTc-UBI 29-41 accumulated in an area not concordant with the abnormal uptake of ^99mTc-MDP on the bone scan. In the latter case a diagnosis of soft-tissue infection was made. Bone infection was confirmed by bone biopsy/culture and by clinical and radiological follow-up.

Results

Final analysis was done in 55 patients. Osteomyelitis was confirmed in 37 patients, and 18 patients were free of bone infection. ^99mTc-UBI 29-41 was positive in all 37 patients and with the bone scan as the reference for the bone identified all osteomyelitic foci (68 in total). ^99mTc-UBI 29-41 was negative for osteomyelitis in all 18 patients, and 17 of these patients were diagnosed with soft-tissue infection (^99mTc-UBI 29-41 accumulation without concordant abnormal uptake on bone scintigraphy). The sensitivity, specificity and accuracy of ^99mTc-UBI 29-41 scan in combination with three-phase bone scan for the diagnosis of osteomyelitis in diabetic foot was 100 %. Accuracy for soft-tissue infection was also 100 %. Maximum accumulation of the ^99mTc-UBI 29-41 with maximum target to background activity was observed in the infectious foci at 30 min after injection.

Conclusion

Tc-UBI 29-41 may be a useful agent for the accurate diagnosis of bone infection in diabetic foot because of the high accuracy demonstrated in this pilot study. It was able to differentiate between bone and soft-tissue involvement effectively in combination with a bone scan.     

Clinical comparison of 99mTc-HMDP and 99mTc-MDP

^99mTc-Hydroxymethylene diphosphonate (HMDP) was compared to ^99mTc-methylene diphosphonate (MDP) with respect to image quality, lesion detectability, and the uptake ratios of normal bone to soft tissue (B/S), metastatic bone to soft tissue (M/S) and bone metastases to normal bone (M/B) at 2 and 3 h after injection in the same subjects. Thirty-three patients with bone metastases were examined in six nuclear-medicine departments, with each center using its usual bone-scanning protocol which was identical for both compounds in the same patient. The uptake of ^99mTc-HMDP in normal bone (B/S) was significantly higher than that of MDP at 2 and 3 h, but there were no significant differences between the two compounds with regard to the M/S or M/B or M/B ratios. The M/B of HMDP at 2 h was not significantly different from that of MDP at 3 h, the latter showing a significantly higher B/S and M/S ratio. All lesions were detected with both compounds, even at 2 h. The image quality was rated as follows (in decreasing order): HMDP (3 h), MDP (3 h), HMDP (2 h), and MDP (2 h). HMDP was shown to be a useful bone-imaging agent, especially when shorter intervals between injection and recording are required.     

89Sr bremsstrahlung single photon emission computed tomography using a gamma camera for bone metastases

Objective

Strontium-89 chloride (⁸⁹Sr) bremsstrahlung single photon emission computed tomography (SPECT) imaging was evaluated for detecting more detailed whole body ⁸⁹Sr distribution.

Methods

⁸⁹Sr bremsstrahlung whole body planar and merged SPECT images were acquired using two-detector SPECT system. Energy window A (100 keV ± 50 %) for planar imaging and energy window A plus adjacent energy window B (300 keV ± 50 %) for SPECT imaging were set on the continuous spectrum. Thirteen patients with multiple bone metastases were evaluated. Bone metastases can be detected with ^99mTc-HMDP whole body planar and merged SPECT images and compared with ⁸⁹Sr bremsstrahlung whole body planar and merged SPECT images. Based on the location of metastatic lesions seen as hot spots on ^99mTc-HMDP images as a reference, the hot spots on ⁸⁹Sr bremsstrahlung images were divided into the same bone parts as ^99mTc-HMDP images (a total of 35 parts in the whole body), and the number of hot spots were counted. We also evaluated the incidence of extra-osseous uptakes in the intestine on ⁸⁹Sr bremsstrahlung whole body planar images.

Results

A total of 195 bone metastatic lesions were detected in both ^99mTc-HMDP whole body planar and merged SPECT images. Detection of hot spot lesions in ⁸⁹Sr merged SPECT images (127 of 195; 66 %) was more frequent than in ⁸⁹Sr whole body planar images (108 of 195; 56 %), based on metastatic bone lesions in ^99mTc-HMDP whole body planar and merged SPECT images. A large intestinal ⁸⁹Sr accumulation was detected in 5 of the 13 patients (38 %).

Conclusions

⁸⁹Sr bremsstrahlung-merged SPECT imaging could be more useful for detailed detection of whole body ⁸⁹Sr distribution than planar imaging. Intestinal ⁸⁹Sr accumulation due to ⁸⁹Sr physiologic excretion was detected in feces for 4 days after tracer injection.     

Clinical utility of technetium-99m methoxisobutylisonitrile imaging in differentiated thyroid carcinoma: comparison with thallium-201 and iodine-131 Na scintigraphy,and serum thyroglobulin quantitation

Recently, technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) has been used to image thyroid carcinoma. A prospective study was performed to compare the efficacy of^99mTc-MIBI to thallium-201 (²⁰¹T1) scintigraphy in patients with differentiated thyroid carcinoma. The clinical utility of all radionuclide imaging modalities, i.e.,^99mTc-MIBI,²⁰¹Tl, and iodine-131 Na (¹³¹I-Na), as well as serum thyroglobulin estimation, was evaluated. Thirty-four post-thyroidectomy patients (age range: 26–76 years) underwent 45 studies. Histopathologies studied included fourteen papillary, eight papillaryfollicular, ten follicular, one Hürthle cell, and one medullary carcinoma of the thyroid. Following optimal stimulation of endogenous thyroid stimulating hormone (i.e, TSH >-50 mU/ml), the patients underwent²⁰¹Tl and^99mTc-MIBI scintigraphy. Concomitant¹³¹I-Na scintigraphy was performed and serum thyroglobulin levels were measured. Sixteen scan sets were performed prior to¹³¹I-Na ablation therapy. Twenty-nine scan sets were performed following¹³¹I-Na ablation therapy. The presence or absence of thyroid cancer was established by clinical, biochemical, radiologic, and/or biopsy findings. There was no significant difference in sensitivity and specificity of²⁰¹Tl scintigraphy versus^99mTc-MIBI scintigraphy in pre- and postablation studies.¹³¹I-Na scintigraphy with determination of thyroglobulin level was sufficient in preablation studies. Among postablation patients, the addition of^99mTc-MIBI or²⁰¹Tl offered a higher diagnostic yield. Between the²⁰¹Tl and^99mTc-MIBI studies, there was a concordance of 69% in preablation and 97% among postablation patients (P=0.027). It is concluded that^99mTc-MIBI is a suitable alternative to²⁰¹Tl scintigraphy in thyroid carcinoma, especially following thyroidectomy and¹³¹I-Na therapy.¹³¹I-Na scintigraphy with serum thyroglobulin is adequate in both pre- and postablation patients. Among the post-¹³¹I-Na ablation patients,^99mTc-MIBI or²⁰¹Tl is extremely valuable for tumor localization, especially when the¹³¹I-Na whole-body scan is negative. The combination of^99mTc-MIBI or²⁰¹Tl scintigraphy with¹³¹I-Na and serum thyroglobulin offers the highest diagnostic yield.This paper is based on a presentation at the 76th Annual Meeting of the American Radium Society, South Hampton, Bermuda, 22–26 April 1994.     

99mTc-HMDP accumulation in a phyllodes tumor of the breast,a case report

In a patient with breast tumor,^99mTc-HMDP accumulation in the tumor was recognized in evaluating bone metastasis. Surgery and histopathology revealed that the tumor was a phyllodes tumor. This scintigraphic finding was thought to be rare and phyllodes tumor should be included in differential diagnosis when^99mTc-HMDP accumulation in the breast was recognized.     

Whole-body iodine-131 metaiodobenzylguanidine imaging for detection of bone metastases in patients with paraganglioma: comparison with bone scintigraphy

Iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) therapy is an effective treatment for patients with malignant paraganglioma for which surgical resection is not indicated. We performed high-dose ¹³¹I-MIBG therapy on two patients with malignant paraganglioma and multiple bone metastases. The bone metastases were diagnosed by magnetic resonance imaging (MRI). Metastatic bone lesions were evaluated by whole-body ¹³¹I-MIBG imaging and bone scintigraphy. Whole-body ¹³¹I-MIBG imaging showed extensive metastatic bone lesions, whereas conventional bone scintigraphy did not. There was a remarkable discrepancy between ¹³¹I-MIBG imaging and bone scintigraphy in the diagnosis of metastatic bone lesions of malignant paraganglioma in our two patients. High-dose ¹³¹I-MIBG imaging may detect early stages of bone metastases, compared with bone scintigraphy, in patients with malignant paraganglioma.