<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.     

<Superscript>131</Superscript>I-MIBG Therapy in metastatic phaeochromocytoma and paraganglioma

Purpose ¹³¹Iodine metaiodobenzylguanidine (¹³¹I-MIBG) is a radiopharmaceutical used for scintigraphic localisation of phaeochromocytomas and paragangliomas. The experience with its therapeutic use is limited. We report our experience for the treatment of malignant phaeochromocytoma and paraganglioma. Materials and methods The charts of 19 patients with malignant phaeochromocytoma (n = 12) or paraganglioma (n = 7), who were treated with ¹³¹I-MIBG, were retrospectively reviewed. Four patients (21%) received radiotherapy, three (16%) chemotherapy, and in one patient (5%), both chemotherapy and radiotherapy was given before ¹³¹I-MIBG therapy. Response to ¹³¹I-MIBG treatment was evaluated by objective as tumour response, biochemical and subjective response. Results Of the 19 patients, 13 (68%) were men, 6 (32%) were women. Ages ranged from 22 to 68 years (median, 47). The median initial dose was 7.4 GBq (200 mCi; range, 6.7 GBq–25.9 GBq, 180–700 mCi); median cumulative dose was 22.2 GBq (600 mCi; range, 6.8 GBq–81.4 GBq, 183–2200 mCi). Objective tumour response was achieved in 47% of the patients. Biochemical response rate was 67%, and symptomatic response was seen in 89% of the patients. Overall median follow-up was 29 months, with a range of 3–93 months. Haematologic complications were the most common side effects and were observed in 26% of the patients. Conclusion Our data support that symptomatic and biochemical response can be reached with ¹³¹I-MIBG therapy in patients with metastatic phaeochromocytoma and paraganglioma. Although complete tumour response was not observed, the palliation and control of tumour function by ¹³¹I-MIBG therapy may be valuable for the patients.     

Detection of metastatic lesions from malignant pheochromocytoma and paraganglioma with diffusion-weighted magnetic resonance imaging: comparison with 18F-FDG positron emission tomography and 123I-MIBG scintigraphy

OBJECTIVE: To investigate the diagnostic features of whole-body diffusion-weighted magnetic resonance imaging (DWI) as compared with 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and (123)I-meta-iodo-benzyl guanidine scintigraphy (MIBG) on metastatic lesions of patients with malignant pheochromocytoma or paraganglioma. METHODS: We prospectively studied 11 patients with histologically confirmed pheochromocytoma/paraganglioma and possible metastatic lesions. FDG-PET, MIBG, and DWI examinations were performed within 1 week, and the images were visually interpreted. Abnormal positive uptake either on MIBG or on FDG-PET was considered as metastases. Abnormal high signal intensities on DWI were considered as metastases using conventional T1-and T2-weighted images as reference. RESULTS: FDG-PET and DWI demonstrated metastatic lesions in all 11 patients, but MIBG showed no metastatic lesions in two patients. The numbers of lymph node metastases depicted on FDG-PET, MIBG, and DWI were 19, 6, and 39; bone metastases were 50, 49, and 60; liver metastases were 9, 9, and 15; lung metastases were 5, 7, and 5, respectively. MIBG failed to demonstrate many metastatic lesions, which were demonstrated on FDG-PET or DWI, although two mediastinal lymph node metastases, three lung metastases, and six bone metastases, which were not seen on DWI, were clearly demonstrated on MIBG. DWI showed 15 liver metastases, but 6 of them were not seen on FDG-PET or MIBG. CONCLUSIONS: DWI may be particularly advantageous in depicting lymph node and liver metastases and may have a higher rate of detecting metastatic lesions when compared with MIBG or FDG-PET. The limitations of DWI were possible false-positive finding, and probable lower detectability of mediastinal lymph node and lung metastasis.     

Diagnostic Performance of 68Ga-DOTATATE PET/CT, 18F-FDG PET/CT and 131I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma

Purpose

To evaluate the diagnostic performance of ⁶⁸Ga-DOTATATE ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT), ¹⁸F-FDG PET/CT and ¹³¹I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma.

Materials and Methods

Seventeen patients (male = 8, female = 9; age range, 13–68 years) with clinically proven or suspicious metastatic pheochromocytoma or paraganglioma were included in this prospective study. Twelve patients underwent all three modalities, whereas five patients underwent ⁶⁸Ga-DOTATATE and ¹³¹I-MIBG without ¹⁸F-FDG. A composite reference standard derived from anatomical and functional imaging findings, along with histopathological information, was used to validate the findings. Results were analysed on a per-patient and on per-lesion basis. Sensitivity and accuracy were assessed using McNemar’s test.

Results

On a per-patient basis, 14/17 patients were detected in ⁶⁸Ga-DOTATATE, 7/17 patients in ¹³¹I-MIBG, and 10/12 patients in ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (93.3 %, 94.1 %), (46.7 %, 52.9 %) and (90.9 %, 91.7 %) respectively. On a per-lesion basis, an overall of 472 positive lesions were detected; of which 432/472 were identified by ⁶⁸Ga-DOTATATE, 74/472 by ¹³¹I-MIBG, and 154/300 (patient, n = 12) by ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (91.5 %, 92.6 % p < 0.0001), (15.7 %, 26.0 % p < 0.0001) and (51.3 %, 57.8 % p < 0.0001) respectively. Discordant lesions were demonstrated on ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG.

Conclusions

Ga-DOTATATE PET/CT shows high diagnostic accuracy than ¹³¹I-MIBG scintigraphy and ¹⁸F-FDG PET/ CT in mapping metastatic pheochromocytoma and paraganglioma.     

Evaluation of (111)In-pentetreotide, (131)I-MIBG and bone scintigraphy in the detection and clinical management of bone metastases in carcinoid disease

Bone metastases are assumed to be rare in carcinoid disease and to be associated mainly with bronchial primaries. The aim of the present study was to evaluate the occurrence of bone metastases in patients with metastatic carcinoid tumours, and the role of various nuclear medicine modalities (bone scintigraphy, (111)In-pentetreotide and (131)I-MIBG) in its detection and clinical management. Nine (2 women, 7 men, median age 65 years) out of 86 consecutive carcinoid patients treated between 1987 and 1998 developed bone metastases (10%) with a median interval of 37 months between the diagnosis of metastatic carcinoid and bone metastases. Seven of them had non-bronchial primaries. (111)In-pentetreotide scintigraphy failed to detect the bone lesions in 50% of the cases, and (131)I-meta-iodobenzylguanidine(MIBG) scintigraphy in almost 80% of cases. Standard bone scintigraphy, however, was positive in all. Pain relief of bone metastases by means of radiation therapy was obtained in 5 of 6 patients. In another patient palliation of pain symptoms was obtained with Rhenium-186-hydroxyethylidene diphosphonate. Octreotide, Interferon of MIBG were ineffective for this purpose. It is concluded that bone metastases in carcinoid patients may be missed on (131)I-MIBG and (111)In-pentetreotide scintigraphy. Bone scintigraphy is a sensitive imaging technique. Diagnostic nuclear medicine modalities may be helpful in the clinical management of carcinoid disease.     

The role of I-131-MIBG in the diagnosis and therapy of carcinoids

The successful use of ¹³¹I-MIBG for the diagnosis and treatment of pheochromocytoma and neuroblastoma has led to its application in patients with carcinoid, another neural crest tumor. The present report describes the scintigraphic findings, in correlation with clinical and biochemical parameters, in 20 patients with histologically proven carcinoids. ¹³¹I-MIBG total body scintigraphy was positive in 12 and equivocal in 1 of 19 patients with metastases. The necessity of delayed imaging and the possible advantage of single photon emission tomography for the detection of this tumor are emphasized. The results of ¹³¹I-MIBG treatment in five patients with progressive carcinoid metastases are discussed. It is concluded that ¹³¹I-MIBG has a role in the work up of patients with proven carcinoid and can be used for palliative treatment of this tumor.     

The role of 99Tcm-sestamibi scintigraphy in the staging and prediction of the therapeutic response of stage IV neuroblastoma: comparison with 131I-MIBG and 99Tcm-MDP scintigraphy

In this study, we investigated prospectively the diagnostic role of 99Tcm-MIBI for staging and for predicting the therapeutic response of stage IV neuroblastoma compared with 131I-MIBG imaging and 99Tcm-MDP bone scintigraphy. Nine patients (4 girls and 5 boys aged 1-7 years) with suspected or proven stage IV neuroblastoma were studied with 99Tcm-MIBI at initial diagnosis and after 12-18 months of multidrug therapy. After the injection of 80 MBq.kg-1 99Tcm-MIBI, early (10 min) and delayed (1 h) images were obtained. The data were correlated with 131I-MIBG scans, bone scintigraphy, ultrasound, computed tomography and/or magnetic resonance imaging, and bone marrow biopsy. Eight of nine primary tumours and 41 metastatic lesions were detected by 131I-MIBG scintigraphy. None of the primary lesions demonstrated significant 99Tcm-MIBI accumulation. Sestamibi was positive in 16 of 41 MIBG-avid metastatic lesions. After six courses of multidrug chemotherapy, 30 131I-MIBI-avid neuroblastoma metastases that were 99Tcm-MIBI-negative at the time of diagnosis still did not show significant sestamibi accumulation. Follow-up demonstrated that all lesions that were 99Tcm-MIBI-avid at the time of diagnosis remained negative. Of these 16 lesions, seven were positive for 131I-MIBG accumulation with no reduction in size, and nine showed resolution after therapy. New metastatic foci detected by MIBG scintigraphy did not accumulate 99Tcm-MIBI. Clinical evaluation of patients with no 99Tcm-MIBI uptake in primary and secondary sites of neuroblastoma confirmed that they were resistant to multidrug chemotherapy. All 99Tcm-MIBI-positive lesions, irrespective of clinical outcome, demonstrated significant clearance of tracer on the delayed images. We conclude that 99Tcm-MIBI has no role in the staging of neuroblastoma. Sestamibi is a well-documented transport substrate for P-glycoprotein-related multidrug resistance and serial imaging may provide prognostic information on the therapeutic value of chemotherapy.     

Prognostic values of initial responses to low-dose 131I-MIBG therapy in patients with malignant pheochromocytoma and paraganglioma

Purpose

We retrospectively examined whether or not initial responses of first low-dose ¹³¹I-meta-iodo-benzyl-guanidine radiotherapy (¹³¹I-MIBG therapy) in patients with malignant pheochromocytoma and paraganglioma had prognostic values.

Materials and methods

This study included 26 patients with malignant pheochromocytoma (n = 18) and paraganglioma (n = 8) who underwent the first ¹³¹I-MIBG therapy between October 2001 and September 2007. Based on the initial subjective, hormonal, scintigraphic, and objective responses to ¹³¹I-MIBG therapy, the responses were divided into progression disease (PD) and non-PD. We examined the following factors for prognostic significance: sex, age, disease, initial diagnosis (benign or malignant pheochromocytoma), hypertension, diabetes mellitus, palpitations, symptoms related to bone metastases, and number of low-dose ¹³¹I-MIBG therapy. Univariate Cox proportional regression analysis was used to identify prognostic factors for overall survival. Overall survival was analyzed by Kaplan–Meier method and the curves were compared using the log-rank test.

Results

The median survival time was 56 months. In the follow-up period, 16 patients died from exacerbation of their diseases. Univariate analysis showed that the hormonal PD [hazard ratio (HR) 3.20, P = 0.034, confidence interval (CI) 1.09–9.93], objective PD (HR 11.89, P = 0.0068, CI 2.14–65.85), single-time ¹³¹I-MIBG therapy (HR 3.22, P = 0.020, CI 1.21–8.79), hypertension (HR 2.93, P = 0.044, CI 1.02–10.50), and symptoms related to bone metastases (HR 3.54, P = 0.023, CI 1.18–13.04) were bad prognostic factors for overall survival. Kaplan–Meier analysis demonstrated that the hormonal non-PD (P = 0.026), objective non-PD (P = 0.0002), multiple-time ¹³¹I-MIBG therapy (P = 0.013), and no symptom related to bone metastases (P = 0.024) were significantly associated with good prognosis. Overall survival rate was 70 and 50 % at 5 years from the initial diagnosis and from the first ¹³¹I-MIBG therapy, respectively.

Conclusion

The hormonal and objective responses to the first low-dose ¹³¹I-MIBG therapy as well as complication of hypertension and symptoms related to bone metastases may be prognostic factors in patients with malignant pheochromocytoma and paraganglioma.     

Comparison of 111In-DOTA-DPhe1-Tyr3-octreotide and 111In-DOTA-lanreotide scintigraphy and dosimetry in patients with neuroendocrine tumours

Purpose Somatostatin receptor scintigraphy with ¹¹¹In-DOTA-DPhe¹-Tyr³-octreotide (¹¹¹In-DOTA-TOC) and ¹¹¹In-DOTA-lanreotide (¹¹¹In-DOTA-LAN) has been used for staging of neuroendocrine tumours (NETs). However, the comparative diagnostic value of these radioligands on a lesion basis has not yet been established. The aim of this study was to compare the diagnostic capacity of ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy in patients with NETs, evaluating whether significant differences exist in lesion imaging with these radioligands. Furthermore, dosimetric data were compared. Methods Forty-five patients with NETs were investigated with ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy. Scintigraphic results were compared with those of conventional imaging and/or surgery in each patient, and also ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in 20 patients. Results ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy were true positive in 42/45 (93%) and 39/45 (87%) patients, and imaged 74/91 (81%) and 73/91 (80%) tumour lesions, respectively. ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN detected liver metastases in 21 and 14 patients, mediastinal metastases in seven and 11 patients, and bone metastases in two and seven patients, respectively. These radioligands revealed lesions not seen by conventional imaging in seven and eight patients, respectively, or by ¹⁸F-FDG-PET in eight and seven patients, respectively. The estimated tumour absorbed doses for ⁹⁰Y-DOTA-TOC were higher than those for ⁹⁰Y-DOTA-LAN in 14 patients, whereas the opposite was true in 12 patients. Conclusion Both ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN are suitable for imaging tumour lesions in patients with NETs and can detect lesions that may not be seen by conventional imaging and ¹⁸F-FDG-PET. Compared with ¹¹¹In-DOTA-LAN, ¹¹¹In-DOTA-TOC has a superior diagnostic capacity for liver metastases, but a lower diagnostic capacity for metastatic lesions in mediastinum and bone.     

Role of whole-body diffusion-weighted MRI in detecting bone metastasis

Purpose

The aim of this study was to compare the results of whole-body diffusion-weighted magnetic resonance (DW-MR) imaging with staging based on computed tomography (CT) and nuclear scintigraphy using Tc99m results as the standard of reference.

Methods and materials

Seventeen patients with known malignant tumours were included in the study. The thorax and the abdomen were imaged using breath-hold diffusion-weighted imaging and T1-weighted imaging sequences in the coronal plane. Location and size of osseous metastases were documented by two experienced radiologists. Whole-body DW-MR imaging findings were compared with results obtained at skeletal scintigraphy and CT bone survey.

Results

The mean examination time for whole-body DW-MR imaging was 25.5 min. All bone metastases regardless of the size were identified with whole-body DW-MR imaging; MR imaging depicted more bone metastases than CT. Skeletal scintigraphy depicted osseous metastases in 13 patients (with greater sensitivity to the lower limb), whereas whole-body DW-MR imaging revealed osseous metastases in 13 patients (with greater sensitivity to the spine). DW-MR did not show good results for detection of rib cage metastases. The additional osseous metastases seen with MR imaging were confirmed at follow-up examinations and some had a change in therapy. MR identified 22 % more metastatic lesions when compared to bone scintigraphy and 119 % when compared to CT. Bone scintigraphy identified 80 % more metastatic lesions when compared to CT. On a per-patient basis, whole-body DW-MR imaging revealed sensitivity and specificity values of 100 %.

Conclusion

Whole-body DW-MR imaging was more sensitive in the detection of osseous metastases than were skeletal scintigraphy and CT bone survey.     

Thallium-201 scintigraphy of neuroblastoma: Different results for primary tumors and skeletal lesions

Thallium-201 scintigraphy was performed in 8 children with neuroblastoma, and uptake by the tumors was evaluated in comparison with the results of 123I-MIBG scintigraphy. No primary tumors or metastatic lymph nodes showed 201Tl accumulation, but in 4 cases of bone marrow metastases accompanied by focal cortical invasion, the metastatic lesion was demonstrated more clearly on the early image than on the delayed image. In another case of bone metastases infiltrating cortical bone revealed by 123I-MIBG scintigraphy and biopsy before treatment, 201Tl scintigraphy performed after chemotherapy showed abnormal accumulation in the tibia, but the second 123I-MIBG scintigraphy performed 1 week after the 201Tl scintigraphy showed no abnormal uptake. 201Tl does not appear to have good affinity for neuroblastoma, but it accumulates in metastatic skeletal lesions. A reactive hypermetabolic bone marrow, and/or inflammatory process and periosteal reaction due to the presence of metastatic foci may have induced the 201Tl accumulation. It seems that 201Tl is not useful for the diagnosis. Nevertheless, the discordance between 201Tl uptake in primary tumors and skeletal lesions allows speculation on the mechanism of 201Tl accumulation in skeletons.     

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.     

Comparison of whole-body STIR-MRI and <Superscript>99m</Superscript>Tc-methylene-diphosphonate scintigraphy in children with suspected multifocal bone lesions

The study was performed to compare whole-body short time inversion recovery (STIR) MR imaging and ^99mTc-methylene diphosphonate planar scintigraphy in the examination of children with suspected multifocal skeletal malignant lesions. Sixteen patients with known or suspected malignant skeletal disease underwent both whole-body STIR MR imaging and bone scintigraphy. The lesions were described and numbered according to scintigraphic evaluation criteria. Thus, 16 regions were analyzed in each patient for the comparison between the two modalities. Histology was proven in the primary malignant regions. Follow-up MRIs were registered. Scintigraphy and MRI follow-up were evaluated as gold standard. A total of 139 different lesions was observed by both modalities. Baseline whole-body MRI revealed 119 bone lesions in 256 possible sites (46.5%); scintigraphy revealed only 58 lesions (22.6%). Congruence was observed in only four patients (25%). According to the location of the lesion, correlation was observed in 39/139 lesions (28%). In all, 57.5% of the lesions were detected only by MRI and 14.5% of the lesions were detected only by scintigraphy. Whole-body MRI was more sensitive (P<0.001). Of all lesions numbered which could be separated in the initial MRI, whole-body MRI detected 178 lesions in the patients. The results suggest that whole-body MRI using a STIR sequence is an effective radiation free method for examination of children with suspected multifocal bone lesions. MRI showed more lesions than conventional ^99mTc-methylene diphosphonate scintigraphy. Therefore, whole-body MRI may be feasible as a screening modality for metastatic and skip lesions in osteosarcoma, PNET, Ewing sarcoma and Langerhans cell histiocytosis in children.     

111In-pentetreotide and123I-MIBG for detection and resection of lymph node metastases of a carcinoid not visualized by CT, MRI or FDG-PET

A patient with a history of a jejunal carcinoid and resection of liver metastases underwent CT, MRI and FDG-PET as well as somatostatin receptor scintigraphy using 111In-pentetreotide during follow-up. Octreoscan demonstrated one extrahepatic abdominal lesion with pathologic uptake, while the other imaging modalities failed to show a corresponding abnormality. For verification of this finding 123I-MIBG scintigraphy was performed. The MIBG scan confirmed the octreotide positive lesion and showed an additional abdominal lesion in the SPECT study. According to the scintigraphic results, radioguided surgery (RGS) was implemented using 123I-MIBG. This resulted in the intra-operative detection of two para- and pre-aortic lymph node metastases by the gamma probe and successful resection. An additional preaortal lymph node, suspicious by palpation, was also removed. Histopathology revealed metastases of a carcinoid tumor in all three specimens. In conclusion, the use of RGS facilitates successful removal of carcinoid metastatic lesions despite negative conventional imaging results. Secondly, 123I-MIBG scintigraphy may provide advantages over octreoscan for preoperative localization as well as radio-guided surgery of neuroendocrine metastatic lesions, if the involved site is located in proximity to highly octreotide-avid organs such as the kidneys or spleen.     

Recent progress in radionuclide therapy

Therapeutic use of radionuclides includes 131I for thyroid cancer and hyperthyroid Graves' disease, 89SrCl3 for metastatic bone tumors, 131I-MIBG for malignant pheochromocytoma and neuroblastoma, and radioimmunotherapies. 131I is concentrated in 60-70% of metastases from differentiated thyroid cancer following total thyroidectomy. Radioiodine uptake in metastatic lesions is greater in younger patients than in older ones. Hypothyroidism is often mild or even absent in patients with a large amount of tumor tissue, indicating that thyroid hormones produced by highly differentiated tumors compensate partially or even completely for hypothyroidism following total thyroidectomy. Adequate uptake of 131I has been reported to be associated with significant reduction in the size and number of metastases, and with lower recurrence and higher survival rates. Other favorable factors for longer survival are younger age, well-differentiated histological type, small disease extent, and early discovery of metastases. Older patients with extensive metastases and/or bulky tumor masses in the bone have a poor prognosis. Therefore, it is important to discover metastases as early as possible, when patients are still young. Long-term follow-up with periodic thyroglobulin measurements and imaging studies is strongly recommended. In Japan, 131I treatment for Graves' disease is performed only in selected patients in whom antithyroid drugs cannot be used because of side effects or not effective, considering the high prevalence of permanent hypothyroidism. 89SrCl3 is useful for reducing pain due to bone metastases of malignant tumors. 131I-MIBG therapy is effective for improvement of QOL in some patients with metastatic malignant pheochromocytoma. Radioimmuno-therapy using anti-CD20 has been used successfully in clinical application in patients with malignant B cell lymphoma.     

The value of bone scintigraphy,bone marrow scintigraphy and fast spin-echo magnetic resonance imaging in staging of patients with malignant solid tumours: a prospective study

The purpose of this prospective study was to define the value of bone scintigraphy (BS), bone marrow scintigraphy (BMS) and the new fast spin-echo (FSE) magnetic resonance imaging (MRI) sequences in screening for bone metastases in patients with solid malignant tumours. It was our particular interest to classify patients into a group with and a group without bone metastases, and not only to compare the absolute number of metastases detected by each method. Thirty-two patients were examined using technetium-99m dicarboxy propane diphosphonate bone scintigraphy, ^99mTc-labelled monoclonal anti-granulocyte antibodies for bone marrow scintigraphy and 1.5 T MRI using T1-weighted and FSE T2-weighted sequences. Against a reference standard obtained by re-evaluation of all clinical and imaging data 1 year after prospective BS, BMS and MRI had been performed, the three imaging modalities were falsely positive in two, eight and two cases and falsely negative in zero and four cases, respectively. BMS was falsely positive in eight patients because of vertebral marrow degeneration which caused photopenic defects which could not be differentiated from metastases. MRI showed these lesions to unequivocally contain fat. BMS and MRI were falsely negative in four cases because of the limited field of examination. In our study the key factor in classifying a patient as bone MI or MO was the possibility of surveying the entire skeleton, as is the case in BS, and not that MRI had a higher sensitivity compared to BS when analysis was on a lesion-by-lesion basis. BMS had the same limitations as MRI because the usual bone marrow distribution resulted in a physiologically limited field of view. We conclude that BS remains the method of choice in staging patients with solid tumours despite the fact that MRI is no longer a time-consuming method using FSE sequences. MRI has a complemantary role if special questions remain. BMS appears to have little value in the detection of bone metastases because of its poor specificity, its limited spatial resolution and its restriction to those areas of the skeleton containing haematopoietic marrow. Correspondence to: G.K. v. Schulthess     

Successful and unsuccessful approaches to imaging carcinoids: Comparison of a radiolabelled tryptophan hydroxylase inhibitor with a tracer of biogenic amine uptake and storage,and a somatostatin analogue

A mouse mastocytoma model was used to determine the biodistribution and tumour uptake of four radiopharmaceuticals developed to target the serotonin synthetic pathway in carcinoid tumours. Three of the compounds were competitive inhibitors of the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. Radiolabelled iodo-dl-phenylalanine (iodine-131 PIPA) was found to have the highest uptake and tumourto-liver ratio. Four patients with known carcinoid tumours were then injected with 0.5 mCi¹³¹I-PIPA and imaged at 1, 4, 24 and 48 h post-injection. The radiopharmaceutical, however, failed to localize in the known tumour sites. This result was in contrast to the authors' experience of¹³¹I- and¹²³I-MIBG imaging of carcinoid tumours. Seven patients with known metastatic carcinoid tumours, two patients with symptoms of recurrence following tumour resection, one patient with completely resected disease, and two patients with a flushing syndrome of uncertain aetiology were studied with¹³¹I-MIBG. Three of the seven patients with known metastatic disease had positive¹³¹I-MIBG scans. Both patients with clinical evidence of recurrent disease had negative scans, as did the patient who was considered to have had complete resection of her primary tumour. The two patients with idiopathic flushing syndrome also had negative scans. Among seven patients imaged with¹²³I-MIBG there were four true-negative scans and one falsenegative, the latter in a patient with biochemical and CT evidence of recurrence. In a seventh patient with distant metastases there was variable uptake in some of the lesions. Four patients were studied with indium-111 penetetreodide. Two patients with metastatic carcinoid disease had positive scans, although hepatic metastases were not seen in one. Another two with idiopathic flushing syndrome had normal studies. The literature suggests that up 50% of carcinoid tumour cases are detected with¹³¹I-MIBG, compared to a sensitivity of 87% reported with somatostatin receptor imaging using¹¹¹In-pentetreotide. The experience with¹²³I-MIBG is much less extensive. The mechanisms of carcinoid tumour localization for each of the three classes of radiotracers are discussed and contrasted to their varying sensitivities. The relative success of¹³¹I-MIBG and¹¹¹In-pentetreotide relative to¹³¹I-PIPA may be related to the fact that¹³¹I-MIBG is actively taken up and stored by the enterochromaffin cells of the tumours and¹¹¹In-pentetreotide binds to cell surface receptors, whereas¹³¹I-PIPA binds to tryptophan hydroxylase, which may be present in quantities too small to permit tumours to be imaged.     

Functional imaging as an aid to decision-making in metastatic paraganglioma

Malignant paraganglioma is a rare and slow growing tumour of neuroendocrine origin. At the time of diagnosis, the tumour is usually widespread, with limited therapeutic options. A variety of functional imaging studies are available for staging the disease, guiding therapy and monitoring treatment response. These include 123I-MIBG or 131I-MIBG, 111In-pentetreotide or 111In-lanreotide (somatostatin analogues), and 18F-FDG positron emission tomography. Various radionuclides, including 131I and 90Y, can be targeted to the tumour using MIBG or pentetreotide. Such targeted radionuclide therapy may provide valuable long-term palliation in such patients. We present two cases with metastatic paragangliomas who had widespread soft tissue and bone metastases. One patient was treatment naive and the second had received previous chemotherapy. The functional imaging work-up performed and the targeted radionuclide therapies considered in these patients are described. Both patients were treated with 131I-MIBG. Partial tumour response and complete symptomatic and hormonal response was achieved in one patient; in the second patient there was no change.     

Clinical Usefulness of 18F-fluoride Bone PET

Purpose

¹⁸F-fluoride bone positron emission tomography (PET) has been reported as a useful bone imaging modality. However, no clinical bone PET study had been performed previously in Korea. The authors investigated the usefulness of ¹⁸F-fluoride bone PET in Korean patients with malignant or benign bone disease.

Methods

Eighteen consecutive patients (eight women, ten men; mean age, 55 ± 12 years) who had undergone ¹⁸F-fluoride bone PET for the evaluation of bone metastasis (n = 13) or benign bone lesions (n = 5) were included. The interpretation of bone lesions on ¹⁸F-fluoride bone PET was determined by consensus of two nuclear medicine physicians, and final results were confirmed using combination of all imaging studies and/or clinical follow-up. The analysis was performed on the basis of lesion group.

Results

Thirteen patients with malignant disease had 15 lesion groups, among which seven were confirmed as metastatic bone lesions and eight were confirmed as non-metastatic lesions. ¹⁸F-fluoride bone PET correctly identified six of seven metastatic lesions (sensitivity, 86%), and seven of eight non-metastatic lesions (specificity, 88%). On the other hand, five patients with benign conditions had five bone lesion groups; four were confirmed as benign bone diseases and the other one was confirmed as not a bone lesion. ¹⁸F-fluoride bone PET showed correct results in all the five lesion groups.

Conclusions

¹⁸F-fluoride bone PET showed promising potential for bone imaging in Korean patients with malignant diseases as well as with various benign bone conditions. Therefore, further studies are required on the diagnostic performance and cost-effectiveness of ¹⁸F-fluoride bone PET.     

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

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