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1 Q J NUCL MED MOL IMAGING 2007;51: Sensitivity of [ 99m Tc]methoxyisobutylisonitrile scan in patients with metastatic differentiated thyroid cancer Aim. The aim of the present study was to evaluate the diagnostic sensitivity of [ 99m Tc]methoxyisobutylisonitrile ([ 99m Tc]MIBI) in a large series of patients with metastatic differentiated thyroid carcinoma (DTC), as compared with 131 I-whole body scan (WBS) and other diagnostic imaging techniques. Methods. Eighty-four patients with known metastases from DTC where recruited during the course of replacement thyroxine therapy and undergone [ 99m Tc]MIBI scan. All patients previously performed a 131 I-WBS with thyroglobulin (Tg) measurement and neck ultrasound or computerized tomography, or magnetic resonance imaging, or bone scan or positron emission tomography (PET) scan. Results. Patients were divided in two groups: group A (n=50) with known metastases and positive at a previous 131 I-WBS and group B (n=34) with known metastases, but negative at 131 I-WBS. All patients had elevated serum Tg level in absence of replacement therapy. Technetium-99m-MIBI scan showed 76.2% sensitivity in detecting metastases, Tg during opotherapy 64.3%, and the other imaging techniques combined 86.9%. Sensitivity of [ 99m Tc]MIBI was greater in metastases without 131 I uptake than in metastases with 131 I uptake, although the difference was not statistically significant. Conclusion. Technetium-99m-MIBI scan improves sensitivity of Tg measurement in patients with suspected metastases from DTC during the course of opotherapy and is a useful alternative to fluorodeoxyglucose-pet or other imaging techniques in patients with elevated serum Tg and negative 131 I-WBS. KEY WORDS: Technetium-99m-methoxyisobutylisonitrile - Thyroideal neoplasms - Thyroglobulin - Whole body scan. G. RONGA 1, G. VENTRONI 1, T. MONTESANO 1, M. FILESI 1, M. CIANCAMERLA 1 A. D. DI NICOLA 1, L. TRAVASCIO 1, A. R. VESTRI 2, A. SIGNORE 1, 3 1Nuclear Medicine Unit, Department of Clinical Sciences La Sapienza University of Rome, Rome, Italy 2Department of Experimental Medicine, La Sapienza University of Rome, Rome, Italy 3Department of Nuclear Medicine and Molecular Imaging University Medical Center Groningen University of Groningen, Groningen, The Netherlands The diagnosis of metastases from differentiated thyroid carcinoma (DTC) is currently achieved by measurement of serum thyroglobulin (Tg), particularly after withdrawal of opotherapy or after administration of recombinant human thyroid stimulating hormone (rh-tsh). Iodine-131-whole body scan (WBS) is still the imaging method of choice for determining the site of metastases and for planning 131 I treatment. 1, 2 In the case of suspected metastases not showing 131 I uptake, it is mandatory to locate the site of these lesions at an early stage, in order to refer the patient to radical surgery and/or other forms of treatment, 3, 4 including radio-guided surgery. To this aim, several radiopharmaceuticals have been proposed including [ 99m Tc] methoxyisobutylisonitrile ([ 99m Tc]MIBI), radiolabelled somatostatin analogues, [ 18 F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) and others. In the last few years, it has been reported that [ 99m Tc]MIBI scintigraphy is more sensitive than 131 I- WBS or [ 201 Tl]Cl. 5, 6 Indeed, the American College of Endocrinology and the American Association of Endocrine Surgeons have recently reported that in patients with advanced DTC additional isotopic Address reprint requests to: G. Ronga, Nuclear Medicine, Department of Clinical Science, Policlinico Umberto I, V.le del Policlinico 155, Rome, Italy. giuseppe.ronga@uniroma1.it 364 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING December 2007

2 SENSITIVITY OF [ 99m TC] METHOXYISOBUTYLISONITRILE SCAN PATIENTS WITH METASTATIC DIFFERENTIATED THYROID CANCER RONGA scans may be of benefit and most clinicians favour Tc-Sestamibi particularly when SPECT imaging is necessary. 7 The use of the [ 99m Tc]MIBI scan, in patients with DTC, offers several advantages: 1) MIBI uptake is TSH-independent, thus avoiding the need to withdraw replacement therapy; 2) the physical and dosimetric characteristics are suitable for γ-camera imaging, allowing the use of single-photon emission computed tomography (SPECT); 3) it is easy to perform, with a good cost/benefit ratio, when routinely used in the nuclear medicine units; 4) can provide a rationale for radio-guided surgery of local recurrences. The aim of our study was to evaluate, in a large case series of DTC patients with elevated Tg levels, the sensitivity of [ 99m Tc]MIBI scan, as compared to other imaging modalities for the localization of metastases, particularly in patients with a negative diagnostic 131 I-WBS. Materials and methods Patients A total of 84 patients with metastatic thyroid cancer (73 papillary and 11 follicular; gender: 36 males, 48 females; mean age: 51.9±10.8 years; range: years; follow-up: 8.2±4 years) were enrolled in the present study. All had total thyroidectomy for DTC and 131 I ablation of residual thyroid tissue. Ablation was complete, as evaluated by a second 131 I-WBS. Patients had high Tg levels during opotherapy (Tgopo) and/or after withdrawal of thyroxine therapy (Tg-wd). All patients also performed a diagnostic 131 I- WBS and, in case of a negative scan, underwent other imaging techniques, depending upon the site to be studied: Doppler ultrasonography for searching local recurrences and cervical lymph node metastases; magnetic resonance imaging (MRI) and/or computed tomography (CT) for searching mediastinal metastases and planar X-ray and/or CT for searching lung metastases, methylene diphosphonate bone scan for searching bone metastases. Thirteen patients also performed a PET scan with 18 F-FDG. TABLE I. Patients in group A and group B. Group A (n=50) All metastases with 131 I uptake Normal or high Tg-opo and high Tg-wd 17 patients with multiple metastatic sites 71 metastatic sites: - 37 loco-regional 11 cervical nodes 18 local recurrences 8 mediastinal nodes - 25 lung - 9 bone institutional threshold of 5 ng/ml (radioimmuno assay) and 2 ng/ml (immunoradiometric assay) was accepted as presence of metastases in absence of residual thyroid tissue. Clinical protocol Planar (20, 60 and 120 min) and SPECT (60 min) images of the neck and chest were recorded on a γ- camera (Elscint APEX-SP4, Haifa, Israel), with a low energy and high resolution collimator, following MBq [ 99m Tc]MIBI intravenously injected. A 20% energy window was centered on the 99m Tc photopeak of 140 kev. Planar images were acquired in a matrix. Data collected were elaborated using a dedicated workstation (GE Healthcare). SPECT was performed using a matrix, 360 circular acquisition, 30 s/step for 60 steps. SPECT data were reconstructed using a Butterworth filtered back projection (cut-off 0.5; order 4-5). Iodine-131-WBS was performed using a linear scanner (Biniscanner Italelettronica, Rome, Italy) 40 days after L-thyroxine withdrawal (TSH >40 µiu/ml) with a diagnostic dose (185 MBq) or 4-5 days after a 131 I therapeutic dose ( MBq). PET, MRI, conventional CT and Doppler ultrasound were performed in other departments, using standard protocols. Group B (n=34) All metastases without 131 I uptake Normal or high Tg-opo and high Tg-wd 14 patients with multiple metastatic sites 50 metastatic sites: - 30 loco-regional 4 cervical nodes 22 local recurrences 4 mediastinal nodes - 16 lung - 4 bone Tg-opo: Tg levels during opotherapy; Tg-wd: Tg levels after withdrawal of thyroxine therapy. Laboratory tests Both serum Tg-opo and Tg-wd were evaluated in all patients. Sensitivity and cut-off of Tg varied according to the kit used in the period of follow-up: the Statistical analysis The results of the MIBI scan and other imaging techniques were compared, both alone and combined with Tg-opo and other imaging techniques. Vol No. 4 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 365

3 RONGA SENSITIVITY OF [ 99m TC] METHOXYISOBUTYLISONITRILE SCAN PATIENTS WITH METASTATIC DIFFERENTIATED THYROID CANCER % MIBI scan With Tg-opo Three experienced nuclear physicians evaluated MIBI scans, blinded to the results of the other imaging techniques: each site of MIBI concentration was considered positive by semiquantitative analysis if the tumor/background radioactivity ratio was >2. Data are reported as mean±sd. Sensitivity and confidence intervals (CI) were calculated with a CIA program. Results Without Tg-opo Other imaging tools Figure 1. Sensitivity of methoxyisobutylisonitrile (MIBI) scan (grey columns) in all 84 patients for detecting metastatic disease versus other diagnostic imaging techniques (dark columns) with and without considering Tg levels during opotherapy (Tg-opo). Based on obtained results, patients were divided in two groups: group A (50 patients having metastases with 131 I uptake) and group B (34 patients having metastases without 131 I uptake, based on high Tg values) (Table I). The MIBI scan was positive in 64/84 patients (sensitivity: 76.2%: 95%CI: 66-84%). Tg-opo was high in 54/84 patients (sensitivity: 64.3%; 95%CI: 54-74%). When MIBI scan and Tg-opo were used together, the presence of metastases was diagnosed in 73/84 patients (sensitivity: 86.9%; 95%CI: 71-91%). All other imaging techniques diagnosed metastases in 63/84 patients (sensitivity: 75%; 95%CI: 65-83%) and, when combined with Tg-opo, in 73/84 patients (sensitivity: 86.9%; 95%CI: 69-90%). Therefore, MIBI scan alone showed the same diagnostic sensitivity than all other imaging techniques together, with or without combined Tg measurement (Figure 1). Nevertheless, when the reliability of detecting each metastatic site was considered, several differences were observed: the other imaging techniques showed better results in the case of bone sites (Z test P=0.006), that were all diagnosed by CT, bone scan or X-rays, and in the case of miliaric lung metastases, all diagnosed by 131 I-WBS, but only 50% by conventional CT and never by MIBI scan (Table II). In patients from group A, sensitivity of MIBI scan alone was 72% (36/50 patients presenting metastases), Tg-opo sensitivity alone was 56% (Z test, P=NS), while combined sensitivity was 86% (43/50 patients, 95%CI: 57-87%). The other imaging techniques (Figure 2) showed overall a similar sensitivity than MIBI scan both alone (72%, 36/50 patients) and combined with Tg-opo (84%, 42/50 patients, 95%CI: 61-90%), but showed a higher sensitivity in detecting cervical nodes (Z test, P=0.027) and bone sites (P=0.004). As far as miliaric lung metastases are concerned (10 patients), all were diagnosed by 131 I-WBS, MIBI was negative in all cases, while the other imaging techniques revealed 50% of these lesions (Table III). Tg-wd was high in all patients (178±189 ng/ml). Tgopo was lower than Tg-wd (68±117 ng/ml), particu- TABLE II. Methoxyisobutylisonitrile scan versus other diagnostic imaging techniques. Metastatic sites No. MIBI+ (%) Other techniques + (%) Z-test (P) Tg-opo (ng/ml) (mean±sd) Local recurrences NS 13.8±7.4 Cervical nodes NS 18±11.5 Mediastinal nodes NS 28.3±15.3 Lung (nodular) NS 121.1±136.1 Lung (miliaric) ±221 Bone ±114.1 MIBI: methoxyisobutylisonitrile; Tg-opo: Tg levels during opotherapy; SD: standard deviation; NS: not significant. 366 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING December 2007

4 SENSITIVITY OF [ 99m TC] METHOXYISOBUTYLISONITRILE SCAN PATIENTS WITH METASTATIC DIFFERENTIATED THYROID CANCER RONGA % MIBI scan With Tg-opo Without Tg-opo Other imaging tools Figure 2. Sensitivity of methoxyisobutylisonitrile (MIBI) scan (grey columns) in 50 patients with 131 I uptaking metastases versus other diagnostic imaging techniques (dark columns) with and without considering Tg levels during opotherapy (Tg-opo). larly in patients with local recurrence or cervical node involvement. In 22 out of 50 patients, Tg-opo was below the pathological threshold. In summary, in group A, the two different diagnostic approaches (MIBI alone or other imaging modalities) showed the same sensitivity and, of course, lower than Tg and 131 I-WBS. In patients from group B, MIBI scan alone showed 82.4% sensitivity (28/34 patients; 95%CI: 73-96%), while Tg-opo alone showed 76.4% sensitivity (26/34 patients; 95%CI: 66-94%); the two techniques combined showed 88.2% sensitivity (30/34 patients; 95%CI: 76-98%). The other imaging techniques (Figure 3) showed overall 79.4% sensitivity without considering Tg-opo (27/34 patients; 95%CI: 73-96%) and 91.2% with Tgopo (31/34 patients; 95%CI: 66-94%) No statistical differences were observed between MIBI scan and the other imaging techniques in the detection of the site of the lesions (Table IV). MIBI failed to detect 8 metastatic sites (4 local recurrences, 4 nodular lung metastases), while the other imaging techniques missed 5 local recurrences. Also in group B, Tg-wd (155±142 ng/ml) was higher than Tg-opo (56±73 ng/ml) in all patients and was higher in lung and bone metastases. In 8/34 patients, Tg-opo was below the pathological threshold. Thirteen patients of this group underwent both MIBI scan (always during suppressive thyroxine therapy) and [ 18 F]FDG PET scan (7 during opotherapy and 6 off opotherapy). MIBI scan was positive in 8 patients, while PET scan was positive only in 2 patients, both during opotherapy (Figures 4 and 5). In conclusions, also in group B as well as in group A, the two different diagnostic approaches (MIBI alone or other imaging modalities) showed similar diagnostic sensitivity. Overall, when considering the ability of MIBI scan to detect metastatic sites, it showed better sensitivity in detecting metastases without 131 I uptake than those with 131 I uptake, but the difference was not statistically significant (82.4% vs 72%; Z test not significant). On the contrary, if MIBI is evaluated with measurement of Tg-opo, a significantly higher sensitivity is observed in cases of metastases without 131 I uptake vs those with 131 I uptake (Z test: P=0.013). False positives with MIBI scan occurred only in 2 cases, both with multiple metastatic sites: in one case, a left ventricular dysfunction, mimicking miliaric lung disease, was observed, and, in the other, a mediastinal uptake was then attributed to the thymus following PET scan. As far as [ 99m Tc]MIBI wash-out in metastatic sites is TABLE III. Detection of metastatic sites with 131 I uptake: methoxyisobutylisonitrile scan versus other diagnostic imaging techniques. Metastatic sites No. MIBI+ (%) Other techniques + (%) Z-test (P) Tg-opo (ng/ml) (mean±sd) Local recurrences NS 9.5±4.9 Cervical nodes ±6.3 Mediastinal nodes NS 32.5±19 Lung (nodular) NS 157±154.5 Lung (miliaric) ±221 Bone ±123.2 MIBI: methoxyisobutylisonitrile; Tg-opo: Tg levels during opotherapy; NS: not significant. Vol No. 4 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 367

5 RONGA SENSITIVITY OF [ 99m TC] METHOXYISOBUTYLISONITRILE SCAN PATIENTS WITH METASTATIC DIFFERENTIATED THYROID CANCER % MIBI scan 91.2 With Tg-opo concerned, the 60-min acquisition showed the highest target/background ratios. Discussion Without Tg-opo Other imaging tools Figure 3. Sensitivity of methoxyisobutylisonitrile (MIBI) scan (grey columns) in 34 patients with non- 131 I uptaking metastases versus other diagnostic imaging techniques (dark columns) with and without considering Tg levels during opotherapy (Tg-opo). MIBI scan and other imaging techniques, depending upon the site to be studied, generally showed the same sensitivity, as far as detection of metastases is concerned in patients with DTC; nevertheless, sensitivity differed when the various sites of metastases were compared. In cervical lymph nodes, the other imaging techniques (generally ultrasound, US) showed a better sensitivity than MIBI, probably because US is more effective in detecting lesions <0.5 cm. In a recently published study, in 200 patients with DTC, carried out during opotherapy, Nemec et al. 8 also found a sensitivity of MIBI of 80.9% for cervical lymph nodes. Seabold et al., 9 in 53 consecutive patients studied without L-thyroxine opotherapy, after surgery and ablation therapy with 131 I, found a large number of false negatives on MIBI scan, particularly in the presence of local residual disease or metastatic lymph nodes <1 cm, also due to the interference from salivary gland activity. On the other hand, Miyamoto et al. 10 reported a very high sensitivity (100%) for MIBI in 27 patients presenting cervical lymph node metastases, but these were all cm in diameter and were studied after opotherapy withdrawal, thus with high thyroid stimulating hormone (TSH) levels. Rubello et al., 11 also found a high sensitivity (93.5%) of MIBI, during suppressive opotherapy, when used to detect cervical metastatic lymph nodes, particularly those not having 131 I uptake (minimum diameter >0.7 cm). In this latter study, sensitivity increased to 97.8%, with an improvement in specificity too, if MIBI scan was combined with US. In our study, MIBI scan showed a good sensitivity only in locating mediastinal nodes, although comparable to the other imaging techniques. In agreement with other authors, the larger size of lymph nodes would enhance their detection by MIBI scan. 4, 8, 10, 11 In bone metastases, MIBI scan showed a significantly lower sensitivity than the other imaging techniques. Indeed, in cases of metastases with 131 I uptake diagnosed by WBS, these, which are usually small, were located by CT, but not by X-rays and poorly by MIBI scan. Only in the very few metastases not showing 131 I uptake, sensitivity of MIBI scan was similar to that of other imaging techniques. As far as bone metastases are concerned, Miyamoto et al. 10 and Rubello et al. 11 reported a sensitivity of 93.5% and 85.7%, respectively. They explained this TABLE IV. Detection of metastatic sites without 131 I uptake: methoxyisobutylisonitrile scan versus other diagnostic imaging techniques. Metastatic sites No. MIBI+ (%) Other techniques + (%) Z-test (P) Tg-opo (ng/ml) (mean±sd) Local recurrences NS 16±1.3 Cervical nodes NS 20±7.6 Mediastinal nodes NS 22±2.8 Lung (nodular) NS 46.6±52.4 Lung (miliaric) Bone NS 150±104.3 MIBI: methoxyisobutylisonitrile; Tg-opo: Tg levels during opotherapy; NS: not significant. 368 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING December 2007

6 SENSITIVITY OF [ 99m TC] METHOXYISOBUTYLISONITRILE SCAN PATIENTS WITH METASTATIC DIFFERENTIATED THYROID CANCER RONGA Figure 4. Images of a patient with 131 I-negative whole body scan and high Tg levels. Methoxyisobutylisonitrile (MIBI) scan at 1 h shows mediastinal metastases (A), as well as magnetic resonance imaging (B), but [ 18 F]FDG-positron emission tomography was negative (C). MIBI scan was repeated after surgery and showed not complete disappearance of mediastinal uptake (D). low sensitivity as due to the small size of the lesions and, on the other hand, as due to the interference from physiological abdominal activity. On the contrary, Nemec et al., 8 in bone metastases with 131 I uptake, reported 100% sensitivity and 98.5% specificity. These results in the detection of bone metastases as well as cervical lymph node metastases might also be due to the low degree of vascularization of the neoplastic tissues and to the low oxidative metabolism during TSH-suppressive opotherapy. As far as lung metastases are concerned, MIBI scan and other imaging techniques showed similar sensitivity in detecting nodular metastases, but a different sensitivity in detecting diffuse miliaric localizations, which were always detected by 131 I-WBS and never by MIBI scan. This finding, also reported by other authors, is probably due to the small size of these lesions. CT has also a very low sensitivity for detecting miliaric lesions (about 50%). Again Miyamoto et al. 10 and Rubello et al. 11 also found a low sensitivity in miliaric localizations (75% and 60%, respectively), while Vol No. 4 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 369

7 RONGA SENSITIVITY OF [ 99m TC] METHOXYISOBUTYLISONITRILE SCAN PATIENTS WITH METASTATIC DIFFERENTIATED THYROID CANCER Figure 5. Images of a patient with 131 I-positive whole body scan (A) and high Tg levels. The local recurrence was positive at [ 18 F]FDG positron emission tomography (PET) (B) and MIBI scan (C), but not detected at ultrasound and magnetic resonance imaging (not shown). The MIBI image shows an area of pathological uptake much larger than that shown by PET. Seabold et al. 9 showed 100% sensitivity, although in 5 patients. Küçük et al. 12 recently reported a sensitivity of MIBI of 63.1% in case of lung metastases (18/19 patients also with 131 I uptaking metastases), without discriminating between nodular and miliaric lesions. MIBI scan shows a good sensitivity in local recurrences, both in those with and without 131 I uptake, thus resulting in a very useful indication to surgery, with or without radioactive probe. This finding is very important, since local recurrences often infiltrate adjacent anatomical sites, sometimes with a lack of 131 I uptake, thus resulting in a silent development over a long time period, with a high risk quoad vitam. 13 Roelants et al., 14 diagnosed only 64% of thyroid remnants by MIBI, suggesting its complementary role with 131 I-WBS for non-complicated cases. Also Rubello et al., 11 after surgery, but before residual ablation by 131 I, demonstrated a low sensitivity in detecting the surgical remnant by MIBI scan (46.2%), while Seabold et al., 9 out of 17 false negative cases, found 14 cases of surgical thyroid remnant. Fujie et al. 15 studied diagnostic efficiency of MIBI in patients with metastases from DTC, both before and after remnant ablation, finding results similar to ours after ablation therapy. Sensitivity of MIBI scan improves if combined with Tg measurement during thyroxine therapy (Tg-opo), 16, 17 suggesting its use in routine patient follow-up, particularly in monitoring the effectiveness of previous therapy, particularly surgery, both for metastases with and without 131 I uptake. In case of metastases without 131I uptake, MIBI scan detected secondary localizations as efficiently as other imaging techniques. In agreement with Rubello et al., 11 since MIBI uptake by neoplastic cells depends mainly on their mitochondrial content, it is tempting to hypothesize the presence of a link between Tg synthesis and the ability to uptake MIBI. It is thus possible to correlate high Tg-opo levels in patients with metastases without 131 I uptake with the better sensitivity of MIBI scan, independently of TSH stimulation. SPECT images always showed a better resolution in detecting metastases: an improvement was observed in the sensitivity over planar images, thus confirming data in the literature, 18, 19 particularly for mediastinal lymph nodes and nodular lung metastases. In our experience, early acquisitions (1 h) showed a better target/background ratio than late acquisitions (2 h), which do not usually add any further information. When comparing [ 18 F]FDG PET and MIBI scan, in the literature, there usually appears to be a preference for the former, particularly in case of metastases without 131 I uptake. 20 Iwata et al. 21 compared results obtained from FDG-PET, MIBI scan and 131 I-WBS in 19 metastatic patients, after opotherapy withdrawal: PET detected 81.3% of the metastatic sites, MIBI 64.5% and 131 I-WBS 68.8%; miliaric lung metastases were 370 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING December 2007

8 SENSITIVITY OF [ 99m TC] METHOXYISOBUTYLISONITRILE SCAN PATIENTS WITH METASTATIC DIFFERENTIATED THYROID CANCER RONGA diagnosed more frequently by high resolution CT than by PET. On the other hand, Fridrich et al. 22 obtained similar results with PET and MIBI scan in 12 patients with DTC, but MIBI scan detected a larger number of metastatic sites, locating at least one metastasis in 2 PET-negative patients. In the present study, 13 patients underwent both PET and MIBI scan; only 2 patients were PET positive while 8 were truly MIBI positive, as confirmed by the other imaging techniques and surgery or biopsy. In our study, false positive MIBI scans were rare and always easily explained. Thus, results of the present investigation suggest that MIBI scan may be usefully used to detect the site of metastases without suppressive opotherapy withdrawal and, when positive, to orient the choice of other imaging modalities, thus sparing human and economic resources. Positivity at MIBI scan can be also used for radio-guided surgery as demonstrated elsewhere. Conclusions From the present data it can be concluded that MIBI scan, performed during opotherapy in the follow-up of DTC, improves the sensitivity of Tg measurement. Thus, MIBI scan: 1) is very useful in patients with metastases without 131 I uptake, guiding the choice of more suitable imaging techniques; 2) is useful in the long-term follow-up of patients with high risk both of local recurrence and/or mediastinal metastases; 3) is not useful in detecting small metastatic lymph nodes and in patients with miliaric lung metastases. Moreover, early acquisition time (1 h) is more likely to detect metastases and SPECT acquisition may play an important role in mediastinal and lung nodular localizations, when a surgical approach has to be taken into consideration. References 1. Mazzaferri E, Jhiang SM. 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