British Journal of Radiology (2004) 77, 347-361
© 2004 British Institute of Radiology
doi: 10.1259/bjr/72600472
99Tcm(V)DMSA scintigraphy in skeletal metastases and superscans arising from various malignancies: diagnosis, treatment monitoring and therapeutic implications
S Basu, MBBS (Hons), DRM, DNB1,
N Nair, MD1,
S Awasare, MSc1,
B P Tiwari, MSc1,
R Asopa, MBBS, DRM1 and
C Nair, PhD2
1 Radiation Medicine Centre, Bhabha Atomic Research Centre and 2 Tata Memorial Hospital, Jerbai Wadia Road, Parel, Bombay 400 012, India
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Abstract
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Skeletal metastases arising from a wide variety of malignancies including a few cases with superscan appearance were evaluated using 99Tcm MDP bone scanning and 99Tcm(V)DMSA scintigraphy. Whole body planar scans were obtained at 3 h and 24 h after injection of 740 MBq 99Tcm MDP and 5 days later at similar times after injection of 555 MBq of 99Tcm(V)DMSA. A qualitative as well as quantitative comparison was made between the 99Tcm MDP bone scan and the 99Tcm(V)DMSA scan in detection of osseous metastases. The reference methods used for discordant or equivocal lesions were correlative morphological imaging modalities, for example additional conventional radiography, CT or MRI. The present pictorial review deals with the results of qualitative analysis of the study. A total of 75 cases have been evaluated. The vignettes illustrated in the present article demonstrate avid 99Tcm(V)DMSA concentration in skeletal metastases from a wide variety of malignancies and thus expand the potential therapeutic indications for 188/186 Re(V)DMSA. The study also demonstrates the valuable supporting role a 99Tcm(V)DMSA scan can play in the confirmation as well as evaluation of the extent of malignant infiltration in a suspected superscan in routine skeletal scintigraphy. In addition, a 99Tcm(V)DMSA scan detected a number of metastatic lesions in and around joints and regions with previous surgical intervention that were inconclusive in the bone scan. The results in a few patients who were available for repeat scintigraphy following treatment, support the convincing evidence that 99Tcm(V)DMSA accumulation may be a sensitive indicator of patient response to therapy. This might have an important bearing in the context of increasing "cold" bisphosphonate usage in the treatment of skeletal metastases, where skeletal scintigraphy with a radiolabelled bisphosphonate derivative can often be fallacious because of competitive inhibition by the non-labelled form.
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Introduction
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With the addition of a potential therapeutic analogue in the form of pentavalent rhenium-188/186 dimercaptosuccinic acid complex [188/186 Re(V)DMSA] in the therapeutic armamentarium of nuclear medicine, 99Tcm(V)DMSA scintigraphy has been explored in recent years in various malignant conditions to predict the therapeutic efficacy of the former. In addition to its well established role in medullary thyroid carcinoma and some other soft tissue tumours, the other arena where it holds considerable promise is the targeting of metastatic bone disease. The structural similarity between 99Tcm(V)DMSA and 188Re(V)DMSA accounts for the similarity of their biodistribution [1, 2], which makes the former very useful in the estimation of tumour and renal dosimetry and thereby in selection of suitable patients for the treatment with the latter. Bone marrow depression continues to be the major dose limiting toxicity in treatment with various radiolabelled biphosphonates for pain palliation. In a recently concluded dose escalation study with 188 Re-HEDP [3], the pain palliative response rates appeared to increase with higher doses, reaching 75% in the patients treated with 4.4 GBq. However, the principal dose limiting side effects noticed were thrombocytopenia and leukopenia. The individual maximum percentage decrease in thrombocytes at 1.3 GBq, 2.6 GBq, 3.3 GBq and 4.4 GBq was reported to be 17%, 40%, 60% and 86%, respectively. Normal bone marrow irradiation does not seem to be a major concern with 188Re(V)DMSA. The mean calculated bone marrow dose with 188Re(V)DMSA was found to be 0.07 mGy MBq–1 [2], as compared with 0.91 mGy MBq–1 for 186Re-HEDP [4, 5], 20 mGy MBq–1 for 89Sr [6], 0.89 mGy MBq–1 for 153Sm-EDTMP [7] and 0.41 mGy MBq–1 for 188Re-HEDP [8]. Since one of our goals was to explore the potential of the therapeutic analogue of 99Tcm(V)DMSA, the above mentioned developments and encouraging findings with 186/188Re(V)DMSA gave an impetus to undertake the present study.
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Materials and methods
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Patients with histologically proven malignant tumour with the 99Tcm MDP bone scan showing or highly suspicious of skeletal metastases (including a superscan pattern), were prospectively recruited into the study after seeking consent. The cases were referred mainly from the neighbouring Tata Memorial Hospital, with a few from outside hospitals. Cases available for repeat scintigraphy were evaluated for efficacy of 99Tcm(V)DMSA scintigraphy in treatment monitoring.
Commercially available kits (containing 1 mg of DMSA and 0.3–0.4 mg of SnCl2.2H2O at pH of 2.5) from the Board of Radiation Isotope and Technology, Bombay, were used for preparation of 99Tcm(V)DMSA by reconstituting the lyophilized kit with 0.2 ml of 3.5% NaHCO3 so as to increase the pH to 7.5–8.0. This was followed by addition of TcO4–. 99Tcm MDP was prepared in the standard procedure by adding pertechnetate to the lyophilized MDP kit from the Board of Radiation Isotope and Technology, Bombay, according to the manufacturer's instructions.
Whole body images/spot views were obtained at 3–4 
h (early scan) and 22–24 h (late scan) after injection of 740 MBq 99Tcm MDP and 5 days later at similar times after injection of 555 MBq of 99Tcm(V)DMSA. Whole body scintigraphy was carried out by whole body sweep with simultaneous anterior and posterior acquisition using a dual headed large rectangular field of view Picker gamma camera (Picker International Inc., Cleveland, OH) with low energy, high resolution collimation and a matrix size of 256 x 1024. The photopeak was kept at 140 keV with a 15% window on either side. Spot views of 500 kilocounts per view were obtained using a single head, large, circular field of view Elscinct gamma camera (Apex 409A; Elscinct Ltd., Haifa, Israel) with a low energy all purpose collimator and matrix size of 256 x 256.
All scintigrams were interpreted visually by two experienced nuclear medicine physicians. Discordant or equivocal lesions were evaluated by other anatomical imaging modalities to reach a consensus opinion.
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Skeletal metastases from primitive neuroectodermal tumour (PNET)
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Case 1
An 18-year-old male diagnosed to have PNET of the right proximal humerus was referred for skeletal evaluation before treatment planning (Figure 1
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Figure 1. (a) 99Tcm MDP bone scan demonstrating increased tracer uptake around an osteolytic area in the proximal end of right humerus and mild increased uptake in the right sacroiliac (SI) joint. (b) 99Tcm(V)DMSA whole body scan of the same patient showing focal concentration in the same region corresponding to that seen in bone scan. (c) Multiplanar MRI of the pelvis showing a tiny focus of high signal intensity in the iliac aspect of the right SI joint in an axial short tau inversion recovery sequence suggestive of metastatic deposit. (d) 99Tcm MDP bone scan and (e) 99Tcm(V)DMSA whole body scan post therapy (chemotherapy and external radiotherapy over the right upper humerus) showing significant reduction of tracer uptake commensurate with the patient's clinical improvement.
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Note, the metastatic lesion in the right sacroiliac (SI) joint in the 99Tcm(V)DMSA whole body scan is more vividly demonstrated compared with the bone scan. After local radiotherapy to the primary and systemic chemotherapy, the lesions seem to be resolved in the 99Tcm(V)DMSA scan.
Case 2
A 22-year-old male suffering from PNET of the left ilium was referred for skeletal survey post chemotherapy. MRI of the pelvis revealing a mass lesion in the superomedial portion of the left iliac blade, crossing the left sacroiliac joint (Figure 2).
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Figure 2. (a) 99Tcm MDP bone scan demonstrating increased tracer uptake in the right skull, left 6th and 7th ribs and left side of pelvis. (b) 99Tcm(V)DMSA whole body scan of the same patient showing focal concentration in the same regions to those seen in bone scan.
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Note, the avid pentavalent DMSA uptake in both primary as well as the metastatic site in PNET.
Case 3
A 21-year-old male presented with progressively increasing multiple swelling in the scalp for a duration of 1 month. CT scan of the head showed multiple calvarial lesions bilaterally in the frontal and parietal bones. There was also a large hyperdense mass in the right frontoparietal region with surrounding oedema which was subsequently excised with a right frontal parasagittal craniotomy leaving behind some residue along the superior sagittal sinus. He subsequently received lower hemibody radiation for pain palliation (Figure 3).
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Figure 3. (a) 99Tcm MDP bone scan (pre radiotherapy) demonstrating increased tracer uptake in the skull, left clavicle medial end, right shoulder, multiple ribs bilaterally, right sacroiliac joint, both sided proximal ends and shafts of the femurs, proximal shaft of right tibia. (b) 99Tcm(V)DMSA whole body scan (pre radiotherapy) of the same patient showing focal concentration in the same regions corresponding to those seen in the bone scan. (c,d) 99Tcm MDP bone scan and 99Tcm(V)DMSA scintigraphy of the same patient post lower hemibody radiation showing considerable reduction in tracer uptake in the metastatic sites in the lower half of the body whereas tracer uptake in the upper half remains the same.
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Skeletal metastases from Ewing's sarcoma
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Case 4
A 15-year-old male diagnosed with Ewing's sarcoma of the right ilium received chemotherapy followed by right sided Type I internal hemipelvectomy. He received chemotherapy with Vincristine, Endoxan and Dactinomycin post surgery. 3 months after completion of chemotherapy, he developed a skull swelling in the right parieto-occipital region and was referred for skeletal evaluation (Figure 4).
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Figure 4. (a) Whole body skeletal survey with 99Tcm MDP showed focal uptake of tracer in the skull, proximal end of left femur, sacrum and right ischium. Non-visualization of right ilium was consistent with history of surgery. (b) 99Tcm(V)DMSA whole body scan at 3 h post injection showed uptake at similar sites. (c) The MRI coronal short tau inversion recovery image reveals hyperintense marrow signal at the proximal end of left femur. (Continued)(d, e) The patient received further chemotherapy and improved symptomatically. A repeat 99Tcm(V)DMSA whole body scan revealed much less concentration in the skull and proximal end of left femur, the sacral concentration was not seen. In view of the clinical and scan findings further chemotherapy was advised. (f) The bone scan after four cycles of chemotherapy continued to show increased uptake at the metastatic sites consistent with the "flare phenomenon".
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Skeletal metastases from embryonal and alveolar rhabdomyosarcoma (RMS)
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Case 5
A 14-year-old female had previously been diagnosed with embryonal rhabdomyosarcoma involving the right alveolus and right vertical ramus of the mandible. She underwent surgical excision (right partial mandibulectomy and reconstruction) of the same and post-operative chemotherapy. 4 months later she was referred for skeletal evaluation (Figure 5).
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Figure 5. (a) 99Tcm MDP bone scan showing focally increased uptake of tracer in the right ilium just above the supra-acetabular margin and the horizontal ramus of the mandible. (b) 99Tcm(V)DMSA whole body scan of the same patient demonstrating abnormal focal concentration in the right ilium corresponding to the lesion seen in the bone scan. There is another increased uptake at the right lateral end of the horizontal ramus of the mandible. (c) MRI of the pelvis (coronal short tau inversion recovery sequence) revealing a focal area of high signal intensity in the right ilium in the supraacetabular region. (d) Orthopantomogram showing evidence of right partial mandibulectomy with silastic implant in situ and patchy sclerosis with few lucent areas involving the horizontal ramus of the mandible adjacent to the irregular cut margins, highly suggestive of recurrent disease.
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Note, the focal uptake of tracer at the excisional margin of the mandible in 99Tcm(V)DMSA scintigraphy is suggestive of recurrence, compared with the relatively diffuse increased uptake of 99Tcm MDP in the entire horizontal ramus which is difficult to classify as due to recurrence or due to previous surgical intervention. The orthopantomogram subsequently proved recurrent disease at the cut margin. The metastatic lesion in the right supraacetabular region is also clearly demonstrated.
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Skeletal metastases arising from various histological subtypes of differentiated papillary and follicular thyroid carcinoma
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Case 6
See Figure 6.
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Figure 6. (a) 99Tcm MDP bone scan, (b) 99TcmDMSA whole body scan (3 h scan) and (c) radiograph of the pelvis of a case of thyroid carcinoma with big osteolytic pelvic metastases. The X-ray of the pelvis (c) shows a large osteolytic lesion involving right iliac bone with an associated soft tissue component. Note abnormal tracer uptake in the 99Tcm(V)DMSA scans at the metastatic site. The histopathological report was of a solid variant of papillary carcinoma with lymph node metastasis.
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Case 7
A 58-year-old male presented with a pathological fracture of the left humerus. A biopsy during plating revealed it to be a metastasis from follicular carcinoma of the thyroid. The patient underwent total thyroidectomy and the histopathology of the thyroid specimen was found to be differentiated papillary carcinoma of the thyroid with a largely follicular and focally trabecular and solid arrangement pattern (Figure 7).
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Figure 7. (a) X-ray of the left humerus showing pathological fracture with evidence of plating, (b) 99Tcm MDP bone scan and (c) 99Tcm(V)DMSA whole body scan (3 h scan).
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Note, the increased tracer uptake throughout the plating in the bone scan whereas the tracer uptake in the 99Tcm(V)DMSA whole body scan seems to be restricted to the proximal end. A post I-131 therapy whole body scan (Figure 7c
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Non iodine concentrating skeletal metastases arising from differentiated thyroid carcinoma
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Case 8
A 60-year-old female was diagnosed to have follicular carcinoma of the thyroid with metastases to the right ilium and sacroiliac joint. Large dose I-131 whole body scans at four previous visits did not show any focally increased concentration anywhere in the body but her serum Thyroglobulin level was elevated on all the occasions. At the time of the images shown here, the patient was on Eltroxin (Figure 8).
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Figure 8. (a) X-ray of the pelvis showing a large osteolytic lesion with sclerotic margins in the right iliac bone, abutting the right sacroiliac joint. A posterior abdomen and pelvis scan with 154 MBq I-131 shows no focal concentration. (b) 99Tcm MDP bone scan of the patient revealing an osteolytic lesion in the right ilium and sacroiliac joint with an increased uptake on the left side (probably representing the sclerotic margin) and the right mandible. (Continued) (c) The 99Tcm(V)DMSA whole body scan of the same patient showing increased concentration of tracer at the osteolytic lesion as well as the mandibular lesion.
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Skeletal metastases from prostatic carcinoma
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Case 9
See Figure 9.
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Figure 9. (a) 99Tcm MDP bone scan, and (b,c) 99Tcm(V)DMSA whole body scan at 3 h (b) and 24 h (c) are illustrated for a case of pro static carcinoma with extensive skeletal metastases. Note the identical focal abnormal tracer uptake at the skeletal metastatic sites in all.
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Skeletal metastases from lung carcinoma
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Case 10
A 60-year-old female suffering from non small cell carcinoma of the left lung, complaining of pain at multiple sites, was referred for skeletal evaluation (Figure 10).
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Figure 10. (a) Whole body skeletal survey with 99Tcm MDP showed focal uptake of tracer in the skull, multiple ribs bilaterally, multiple vertebrae, both sides of the pelvis and upper end of left femur. (b,c) 99Tcm(V)DMSA whole body scan at 3 h post injection (b) and 24 h (c) showed uptake at similar sites.
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Skeletal metastases from breast carcinoma
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Case 11
See Figure 11.
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Figure 11. (a) 99Tcm MDP bone scan, and (b,c) 99Tcm(V)DMSA whole body scan at 3 h (b) and 24 h (c) are illustrated for a case of breast carcinoma with numerous skeletal metastases. Note the identical focal abnormal tracer uptake by the two tracers at the various metastatic sites.
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Skeletal metastases from nasopharyngeal carcinoma
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Case 12
A 15-year-old male diagnosed with nasopharyngeal carcinoma developed right sided low backache while on external radiotherapy. His X-ray of the pelvis had been reported normal 1 month previous (Figure 12).
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Figure 12. (a) 99Tcm MDP bone scan and (b) 99Tcm(V)DMSA whole body scan at 3 h post injection both showing increased tracer uptake in the left iliac crest and L3 vertebra.
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Skeletal metastases from malignant melanoma
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Case 13
A 50-year-old male had presented with left sided inguinal nodes and underwent left groin dissection for the same previously. The histopathology of the dissected lymph nodes was found to be metastatic malignant melanoma. Chemotherapy had been recommended but not taken. At the time of the scans he had returned with left anterior chest wall swelling (Figure 13).
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Figure 13. (a) 99Tcm MDP bone scan showing focally increased tracer concentration at the proximal end of the left tibia and a diffuse tracer uptake in the medial aspect of left upper thigh and left mid leg. (b) 99Tcm(V)DMSA whole body scan revealing tracer uptake at the same region and several other regions. The patient was referred for further work-up and metastases in these soft tissue areas were confirmed.
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Skeletal metastases from medullary carcinoma of the thyroid
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Case 14
A 35-year-old female presented with a left sided cervicothoracic mass and diarrhoea. Biopsy from the neck mass revealed a metastatic medullary carcinoma of the thyroid. The serum calcitonin level was 551 977 pg ml–1 (normal range 0–50 pg ml–1). A CT scan of neck and chest revealed a large left neck mass lesion with superior extension in the jugulodigastric region and inferior extension into the anterior and posterior mediastinum to the level of the ascending aorta. There were multiple small calcified hepatic lesions and a heterogeneously enhancing left lobe lesion. A I-131 MIBG scan of the patient did not show any concentration anywhere in the body (Figure 14).
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Figure 14. (a) 99Tcm MDP bone scan of the same patient showing increased uptake in the skull, lower end of sternum, upper end of left humerus and right femoral shaft. 99Tcm(V)DMSA whole body scan at 3 h (b) and at 24 h (c) of the same patient showing increased concentration of tracer in the metastatic areas corresponding to those seen in the bone scan along with increased uptake in the metastatic cervicothoracic mass and hepatic lesions.
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Skeletal metastases with superscan appearance in the conventional bone scan
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See Figures 15–17.
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Figures 15–17. (a) 99Tcm MDP scintigrams of three patients with superscan appearance in the bone. In all of them the kidneys were either not visualized or were very faintly visualized. (b) 99Tcm(V)DMSA whole body scan at 3 h post injection showed diffusely increased tracer uptake in almost the entire axial skeleton and a few areas of focally increased uptake corresponding to those in the bone scans. Both the kidneys were well visualized in all three cases. Note the extent of skeletal involvement in the superscans cited is variable. This can be interpreted with a greater degree of certainty from the 99Tcm(V)DMSA scans, e.g. in Figure 16 the forearms distal to the lower end of both humeri are not involved, which is clearly depicted in 99Tcm(V)DMSA scintigraphy as only soft tissue visualization. This helps in better assessment of disease activity as well as better treatment monitoring.
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Discussion
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Developed initially as a general tumour seeking radiopharmaceutical [9], the main clinical application of 99Tcm(V)DMSA subsequently changed into detection of primary and metastatic medullary thyroid carcinoma (MCT), with a reported sensitivity ranging from 50% to 80% [10–12]. Despite its widespread use, the uptake mechanism of 99Tcm(V)DMSA remains enigmatic. Several factors, including increased blood flow, phosphate metabolism and pH levels are postulated to play an important role in the localization process [13–16].
99Tcm(V)DMSA exists in three isomeric forms [17], each demonstrating different biodistribution from the whole radiopharmaceutical [18]. There seems to be a considerable variation in the isomeric composition in different DMSA kits [18], which may be responsible for the wide range of reported sensitivities in MCT in various studies. It is also claimed that the Amersham DMSA kit (Amerscan DMSA agent; Amersham International, London, UK) yields the most successful tumour imaging results [19].
The normal uptake of 99Tcm(V)DMSA is seen in nasal mucosa, female breasts, blood pool activity (at 3 h) and the kidneys. It is also actively taken up by the growth plates of the growing bones, as evidenced in a number of illustrations of the paediatric age group cited in the article. The blood pool activity seen in the 3 h images is not evident in the 24 h images. The fact that normal bone is indistinguishable from background soft tissue in both early and delayed images is of immense value in dosimetric considerations for minimizing the dose-limiting normal bone marrow toxicity. As evident in this pictorial review and some other previous studies [20, 21], renal radiation dose might be a matter of concern. In one study [2], renal radiation dose was estimated to be 0.5–1.3 mGy MBq–1 using MIRDOSE 3 (a personal computer based program used for internal radionuclide radiation dosimetry according to the Medical Internal Radiation Dose Committee formalism), not different from that of 188Re-HEDP [22]. Various approaches to reduce renal uptake have met with varying success [23, 24]. Using sodium metabisulphite instead of stannous chloride as reducing agent for the formulation of 186Re(V)DMSA, highly significant reduction in renal uptake was achieved in animals [23]. In another study, "cold" DMSA pre-dosing significantly reduced renal uptake [24]. The reason for finding considerably more blood pool activity at 3 h in some patients compared with that in others could be related to the avidity of the metastatic lesions for the tracer or metastatic burden. However, in all cases the 24 h scan demonstrated complete clearance of blood pool activity.
Diagnosis and evaluation of extent of skeletal involvement in superscan pattern
Symmetric, homogeneous uptake of tracer throughout the skeleton coupled with an enhanced ratio of bone to soft tissue activity and faint or absent renal activity has been defined as the superscan pattern. Faint renal visualization, albeit important, cannot be taken as the sole recognition criterion for a superscan. Associated poor renal function and children with intense epiphyseal uptake can often demonstrate reduced or absent renal visualization whereas ureteric obstruction in prostatic carcinoma can lead to false negative scans. Only one study evaluating pentavalent DMSA in superscans has been performed [21], and this did not address the issue of prediction of the extent of skeletal involvement in superscan pattern. In a malignant superscan, the whole skeleton is not necessarily involved and in many cases the peripheral skeleton is spared. Our results suggest that 99Tcm(V)DMSA scintigraphy can play a valuable complimentary role in evaluating the extent of malignant involvement in the superscan with much greater confidence. This is important when assessing the metastatic burden at various points of the disease process, as well as the efficacy of any therapeutic intervention.
Treatment monitoring in skeletal malignancy
Availability of a reliable and inexpensive method to assess treatment response in both primary and metastatic skeletal disease can have a significant impact on patient management. Though routine clinical examination, assay of various tumour and biochemical markers and serial conventional radiography have all proved useful, the bone scan remains the cornerstone of evaluation of skeletal malignancy in clinical practice. This is because it is a highly sensitive, cost effective and non-invasive means to evaluate the whole body skeleton in a single examination. However, several drawbacks of this modality, particularly in treatment monitoring, need to be addressed. The basic principle of the bone scan itself is one of its limitations in monitoring treatment, as it is an indirect measure of tumour activity, being mainly dependent on local osteoblastic reaction. In a patient with metastatic disease it may not be possible to evaluate response in the initial months by bone scan, since apparent deterioration in scan findings may reflect the "flare response" to therapy. In order to evaluate therapeutic response adequately, there should be a delay of at least 6 months, and perhaps a little longer, between scans. A tumour specific radiopharmaceutical would directly assess tumour viability and theoretically the flare phenomenon should be appropriately distinguished from progressive disease. Currently data are sparse in this area but our preliminary data are encouraging and justify a wider trial.
The therapeutic implications
Pentavalent rhenium-188/186 dimercaptosuccinic acid [188/186 Re(V)DMSA] are the beta emitting analogues of 99Tcm(V)DMSA and could be useful agents for systemic radiotherapy. Initial studies [1, 2, 15] have shown similar pharmacokinetics between 99Tcm(V)DMSA and 188/186 Re(V)DMSA. The feasibility of on-demand availability of 188Re from a tungsten 188/rhenium 188 generator, the favourable physical characteristics of 188 Re—high energy beta emission at 2.12 MeV with a 15% abundance of 155 keV gamma emission—makes it an attractive therapeutic radionuclide. The gamma emission makes it possible to conduct post-therapeutic imaging. In a study addressing the pharmacokinetics of 188 Re(V)DMSA [2], the images were found to be strongly reminiscent of 99Tcm(V)DMSA scans in similar patients. It is concluded that 99Tcm(V)DMSA scans are predictive of 188 Re(V)DMSA biodistribution and could be used to estimate tumour and renal dosimetry and assess suitability of patients for 188 Re(V)DMSA treatment [15]. Of the normal tissues, the kidneys received the highest radiation dose (0.5–1.3 mGy MBq–1) [2]. As evidenced in the present study, uptake in the normal bone is not greater than in surrounding soft tissues. This has significant implication in reducing myelotoxicity, the primary adverse event noted when treating with other unsealed sources. High-performance liquid chromatographic analysis of blood and urine showed no evidence of 188 Re in any chemical form other than 188 Re(V)DMSA upto 24 h [2]. Recently, a simple lyophilized kit has also been developed, which provides a convenient method for the preparation of 188 Re(V)DMSA for clinical use [2]. The cases presented widen the therapeutic potential of 188 Re(V)DMSA in skeletal metastases from a variety of malignancies.
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Conclusion
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Our results indicate that there is a striking similarity between 99Tcm(V)DMSA whole body scintigraphy and 99Tcm-MDP uptake in skeletal metastasis arising from a wide spectrum of malignancies. Due to the fact that 99Tcm(V)DMSA is not taken up by the normal bone, the contrast in a metastasis compared with the surrounding uptake is greater, which might be of more diagnostic value than the regular bone image in demonstrating metastatic lesions around various joints and regions with previous surgical intervention. This is evident in a number of illustrations in this pictorial review. In cases of PNET the primaries also demonstrated avid 99Tcm(V)DMSA uptake. In a solitary case of malignant melanoma, 99Tcm(V)DMSA uptake was seen in metastatic lymph nodes and soft tissue in addition to the skeletal metastasis. Its role in confirming a suspicious superscan on conventional skeletal scintigraphy cannot be overemphasized. The preliminary data in a few patients indicate the usefulness of this modality in estimating disease activity as well as treatment monitoring. Without doubt, the strength of its therapeutic analogue labelled with either 188-Re or 186-Re lies in the low normal bone marrow dose, although the renal dose might be a matter of concern. This can, of course, be predicted a priori from extrapolation of data from quantitative 99Tcm(V)DMSA scintigraphy. Novel approaches need to be explored to minimize the renal uptake of the agent. This would have a significant impact on the routine therapeutic use of 186/188 Re(V)DMSA.
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Acknowledgments
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The authors thank all the patients who participated in the study and gratefully acknowledge Mr S J Lohar for preparing the illustrations coupled with helpful suggestions while preparing the atlas.
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Footnotes
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The work has been presented in the Medical and Health session of International Nuclear Conference, 2002 held on 14–18 October, 2002, PWTC, Kuala Lumpur, Malaysia. 
Received for publication March 19, 2003.
Revision received December 9, 2003.
Accepted for publication December 23, 2003.
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Abstract
Introduction
