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Imaging of metastatic melanoma utilising a technetium-99m labelled RGD-containing synthetic peptide.

Integrins are cell-surface glycoproteins found in different forms on all cells except erythrocytes. Integrins bind to cell adhesion molecules and to proteins found in the extracellular matrix. A tripeptidic sequence Arg-Gly-Asp (RGD) is often the primary site of recognition by integrins which are expressed on tumour cells and are responsible for tumour invasion and metastasis. A synthetic decapeptide designated alpha P2 containing two RGD sequences radiolabelled with technetium-99m was used to image malignant melanoma in vivo. Fourteen patients previously diagnosed with metastatic melanoma underwent gamma camera imaging 20-180 min following intravenous administration of the radiolabelled synthetic decapeptide alpha P2. Six out of eight (6/8) of the lymph node metastases (75%) and all other neoplastic sites (11 sites) were successfully imaged, with the exception of three sites in the mediastinal area which were not positively imaged. In two cases there was false positive uptake in the rounded pigmented areolar/nipple area. In three cases (seven sites) the peptide scan confirmed the absence of disease in suspected lesions (true-negative). The synthetic peptide was rapidly removed from the circulation by filtration through the kidneys and excretion in the urine. No toxicity or adverse events were recorded. Radiolabelled alpha P2 peptide, which binds specifically to adhesion molecules on tumours, can be used for the in vivo detection of neoplastic metastases.

Adult↗

Imaging of brain tumors in AIDS patients by means of dual-isotope thallium-201 and technetium-99m sestamibi single-photon emission tomography.

Our aim was to evaluate the use of dual-isotope thallium-201 (Tl) and technetium-99m sestamibi (sestamibi) simultaneous acquisition in brain single-photon emission tomography (SPET) for the differentiation between brain lymphoma and benign central nervous system (CNS) lesions in AIDS patients. Thirty-six consecutive patients with enhancing mass lesions on magnetic resonance (MR) imaging were included in the study. SPET of the brain was performed to obtain simultaneous Tl and sestamibi images. Regions-of-interest were drawn around the lesion and on the contralateral side to calculate uptake ratios. The final diagnosis was reached by pathologic findings in 17 patients and clinical and/or MR follow-up in 19 patients. Of the 36 patients, 11 had brain lymphoma, 1 glioblastoma multiforme, 15 toxoplasmosis and 9 other benign CNS lesions. Correlation between SPET and the final diagnosis revealed in 10 true-positive, 23 true-negative, 1 false-positive and 2 false-negative studies. All patients with toxoplasmosis had negative scans. A patient with a purulent infection had positive scans. Tl and sestamibi scans were concordant in every lesion. The same lesions that took up Tl were also visualized with sestamibi. However, sestamibi scans showed higher lesion-to-normal tissue uptake ratios (3.7 +/- 1.8) compared with those of Tl (2.3 +/- 0.8, P < 0.002). Simultaneous acquisition of Tl and sestamibi can help differentiate CNS lymphoma from benign brain lesions in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Biological consequences of the heterogeneous irradiation of lymphocytes during technetium-99m hexamethylpropylene amine oxime white blood cell labelling.

Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelling of white blood cells, routinely used for the detection of infection, results in the incorporation of radioactivity by polymorphonuclear leucocytes and also lymphocytes and can induce cell lesions in the latter case. The aim of this study was therefore to acquire data on the morphological and functional status of labelled lymphocytes present in the 99mTc-HMPAO leucocyte mixture and to determine the cellular consequences of labelling. The mean radioactivity associated with lymphocytes was 325 +/- 10.8 kBq/10(6) lymphocytes under standard labelling conditions. Microautoradiographic studies showed that labelling was heterogeneous (4% intensely labelled cells), which prevented calculation of the mean absorbed dose. The frequency of chromosomal aberrations (dicentrics and rings) in the labelled lymphocytes for 380 kBq/10(6) cells was 1.08 +/- 0.09 but no abnormality was observed in the unlabelled control lymphocytes. The plating efficiency of labelled lymphocytes was reduced, as compared with that for control cells, but some lymphocytes were still able to form clones and were still "alive" by radiobiological definition. It is therefore suggested that lymphocytes should be removed from 99mTc-HMPAO cell preparations before administration to patients.

Autoradiography↗

Simultaneous acquisition of iodine-123 emission and technetium-99m transmission data for quantitative brain single-photon emission tomographic imaging.

The aim of this study was to obtain quantitative iodine-123 brain single-photon emission tomographic (SPET) images with scatter and attenuation correction. We used a triple-headed SPET gamma camera system equipped with fan-beam collimators with a technetium-99m line transmission source placed at one of the focal lines of the fan-beam collimators. Four energy windows were employed for data acquisition: (a) 126-132 keV, (b) 132-143 keV, (c) 143-175 keV and (d) 175-186 keV. A simultaneous transmission-emission computed tomography scan (TCT-ECT) was carried out for a brain phantom containing 123I solution. The triple energy window scatter correction was applied to the 123I ECT data measured by means of the windows (b), (c) and (d) acquired by two detectors. Attenuation maps were reconstructed from 99mTc TCT data measured by means of the windows (a), (b) and (c) acquired by one detector. Chang's iterative attenuation correction method using the attenuation maps was applied to the 123I ECT images. In the phantom study cross-calibrated SPET values obtained with the simultaneous mode were almost equal to those obtained with the sequential mode, and they were close to the true value, within an error range of 5.5%. In the human study corrected images showed a higher grey-to-white matter count ratio and relatively higher uptake in the cerebellum, basal ganglia and thalamus than uncorrected images. We conclude that this correction method provides improved quantification and quality of SPET images and that the method is clinically practical because it requires only a single scan with a 99mTc external source.

Algorithms↗

Technetium-99m sestamibi brain single-photon emission tomography for detection of recurrent gliomas after radiation therapy.

Technetium-99m sestamibi (MIBI), an alternative radiopharmaceutical for myocardial perfusion imaging, has also been proposed for use as an imaging agent for various tumours, including breast cancer, lung cancer, lymphomas, melanomas and brain tumours. After routine radiation therapy, deteriorating clinical status or treatment failure may be due to either radiation-induced changes or recurrent tumour. Computed tomography and magnetic resonance imaging offer imperfect discrimination of tumour viability and radionecrosis. Against this background we undertook a retrospective study of 35 malignant glioma patients in whom clinical deterioration had occurred, in order to clarify the value of 99mTc-MIBI SPET in identifying tumour recurrence. SPET was performed 15 min after intravenous injection of 1110 MBq with a dual-headed gamma camera using a fan-beam collimator. Transverse, coronal and sagittal views were reconstructed. Intense MIBI uptake was found in 31 patients. This uptake was correlated with tumour recurrence as proved by histology and/or rapid, fatal evolution of these cases. The statistical analysis performed on this population of patients with MIBI uptake revealed a group of patients with a long mean survival and a group with a short mean survival. Two subgroups were found within each of these groups, according to the functional index ratio (tumour uptake/pituitary gland uptake ratio). No MIBI uptake was found in four patients who are still alive and can be considered to be disease-free. In those cases showing MIBI uptake, death occurred an average of 6.69 months following brain SPET. According to our results, the specificity and sensitivity of 99mTc-MIBI brain SPET seem to be high. Moreover, this technique is more accurate than computed tomography or magnetic resonance imaging for discriminating between tumour recurrence and radionecrosis.

Adult↗

Influence of technetium-99m-hexamethylpropylene amine oxime injection time on single-photon emission tomography perfusion changes in epilepsy.

By digitally computing perfusion changes from ictal or postictal (peri-ictal) injections referenced to those acquired interictally, an enhanced method for localizing the epileptogenic area is reported. Computer-based image processing methods for quantifying regional percent change in the brain are applied to a group of 19 epilepsy patients after the injection of technetium-99m hexamethylpropylene amine oxime (HMPAO) and after acquiring single-photon emission tomography (SPET) data. Each patient's region of epileptogenesis was independently localized through pathology and/or successful surgery. The positive and negative quantitative perfusion changes were plotted as a function of the time of the 99mTc-HMPAO ictal injection. This time scale was normalized relative to the seizure duration and is referenced to the time of seizure termination. Eight patients, injected ictally, demonstrated perfusion increases of 25%-100% in the area of known epileptogenesis. Five patients, injected immediately after seizure cessation, demonstrated excessive perfusion decreases of 30%-92% associated with the region of seizure onset. Six patients, injected well after seizure termination, demonstrated hypoperfusion changes less than 30% at the epileptogenic area. Observations on perfusion changes calculated from 99mTc-HMPAO SPET scans, as a function of normalized time, support a progression from ictal hyper- to excessive hypo-, then finally to persistent interictal hypoperfusion. By applying this perfusion pattern model and by noting the time of injection for peri-ictal images, an improved method for localizing the epileptogenic area is demonstrated.

Adult↗

Evaluation of dysthymic disorder with technetium-99 m hexamethylpropylene amine oxime brain single-photon emission tomography.

Dysthymic disorder is a chronic disorder characterised by the presence of a depressed mood and is classified as a distinct category in DSM-IV, separately from major depression. Although brain imaging studies have been performed in major depressive disease, there have to date been no reports of such studies in dysthymic disorder. In this study 36 patients with dysthymic disorder were compared with 16 normal subjects using technetium-99m hexamethylpropylene amine oxime brain single-photon emission tomography. A relative blood flow ratio was calculated for each region of interest using the average tissue activity in the region divided by activity in the cerebellum. There were significant differences in the bilateral inferior frontal, bilateral parietal, right superior frontal and left posterior temporal regions in the patients with dysthymic disorder compared with the healthy controls. These findings support the hypothesis that the biological bases for dysthymic disorder and major depression are similar. Recognition of these regional abnormalities may have clinical utility in both the diagnosis and the treatment of dysthymic disorder. Further studies are needed to confirm our results and to assess the influence of treatment in patients with dysthymic disorder.

Adult↗

Deposition of aqueous aerosol of technetium-99m diethylene triamine penta-acetic acid generated and delivered by a novel system (AERx) in healthy subjects.

Deposition of technetium-99m diethylene triamine penta-acetic acid aqueous radioaerosols generated by a novel aerosol delivery system (AERx) was studied in six healthy subjects using both planar and single-photon emission tomography (SPET) imaging. AERx is a microprocessor-controlled, bolus inhalation device that is actuated at pre-programmed values of inspiratory flow rate and volume. The aims of the study were to determine the effects of posture and inhaled volume upon deposition of the aerosol in the lungs. Each subject inhaled the radioaerosol in two positions (supine vs sitting) and with two inspiratory manoeuvres [vital capacity (VC) vs "fixed volume" of 1 l above functional residual capacity]. Simultaneous transmission-emission planar and tomographic images were acquired. The results showed diffuse deposition of the aerosol in the lung. Neither the breathing manoeuvre nor the posture was found to affect the distribution of the aerosol as measured by the ratio of the activity (counts per pixel) in the peripheral:central (penetration index, PI) or in the apex:base regions of the planar lung images (P>0.1). A small, albeit statistically significant, difference in PI (P<0.03) was found between VC and fixed volume sitting manoeuvres with SPET only. The PI values themselves indicate that the radioaerosol was well distributed in the lung, with the periphery having 45%-64% of the activity of the central region. Superposition of transmission SPET lung outline on emission SPET visually confirmed the excellent peripheral deposition of the aerosol. The AERx system showed high efficiency of delivery, with approximately 50% of the extruded dose in the device depositing in the lung. The uniformity of radioactivity distributed throughout the lung is attributed to the fine particle size (mass median aerodynamic diameter of 2 microm) of the aerosol and the electronic control of aerosol inhalation by the device. In conclusion, the AERx system can be ideal for diffuse aerosol deposition of therapeutic or diagnostic agents and is largely unaffected by inhaled volume and posture. The efficiency of the device device can limit the total radiation exposure of patients and staff administering the radioaerosols, and can make it suitable for delivery of expensive drugs.

Adult↗

Evaluation of flow characteristics of soft-tissue vascular malformations using technetium-99m labelled red blood cells.

The estimation of intralesional haemodynamics is crucial in determining appropriate treatment for soft-tissue vascular malformations. The aim of this study was to develop a method to evaluate the flow characteristics of soft-tissue vascular malformations using technetium-99m labelled red blood cells (99mTc-RBCs). Seventy-nine soft-tissue vascular malformations, including 20 arteriovenous malformations and 59 venous malformations, in 57 patients were examined. Following the intravenous injection of 99mTc-RBCs, dynamic imaging was performed for 30 min with the lesion in the field of view (99mTc-RBC flow study). A time-activity curve was generated for the lesion, and the lesion was categorized as a high-flow or low-flow lesion by visual inspection of the curve. In low-flow lesions, mean vascular transit time (MTT) was calculated by curve fitting based on a two-compartment model. Twenty-nine lesions in 19 patients were examined twice, and reproducibility was assessed. In 23 venous malformations in 16 patients, 99mTc-Sn colloid was percutaneously injected into the intravascular space of the lesion, and dynamic data of 5-min duration were acquired (direct puncture scintigraphy). MTT was estimated from the washout curve and compared with MTT estimated by 99mTc-RBC flow study. 99mTc-RBC flow study classified all 20 arteriovenous malformations as high-flow lesions and all 59 venous malformations as low-flow lesions. In the low-flow lesions, MTT estimated by 99mTc-RBC flow study ranged from 61.2 to 2174.9 s. In the reproducibility study, complete concordance in classification and high correlation in MTT were shown between the first and second examinations. MTT estimated by 99mTc-RBC flow study was significantly correlated with that estimated by direct puncture scintigraphy. In summary, 99mTc-RBC flow study provides a quantitative indicator of intralesional haemodynamics in low-flow lesions in addition to accurate distinction between high-flow and low-flow lesions. The results of this study suggest the feasibility of detailed evaluation of flow characteristics in soft-tissue vascular malformations using 99mTc-RBCs.

Adolescent↗

Technetium-99m sestamibi imaging in paediatric neuroblastoma and ganglioneuroma and its relation to P-glycoprotein.

Imaging with technetium-99m sestamibi offers a non-invasive approach to detect the presence of functional P-glycoprotein (Pgp), one of the major causes of multidrug resistance, in human malignancies. A clinical role for Pgp has been suggested in the subpopulation of primary neuroblastoma without amplification of the proto-oncogene MYCN. We wanted to evaluate the usefulness of 99mTc-sestamibi scintigraphy in the screening of neural crest tumours for the presence of Pgp. In ten children suffering from MYCN-negative neuroblastoma, ganglioneuroblastoma or ganglioneuroma, 99mTc-sestamibi imaging was performed at initial diagnosis. All patients underwent planar imaging 20-30 min and 3.5-4 h after intravenous injection of 740 MBq/1.73 m2 99mTc-sestamibi. Tumour to normal tissue ratios, as well as washout rates, were determined and compared with in vitro flow cytometric analysis of Pgp expression and function. Pgp expression was analysed flow cytometrically with the monoclonal antibodies 4E3 and MRK16, and Pgp function was evaluated by means of rhodamine 123 uptake and efflux either in the absence or in the presence of the Pgp inhibitor verapamil. In nine of ten patients, we found that the intratumoral 99mTc-sestamibi activity was comparable to the background activity, which might be suggestive of Pgp presence. This was confirmed flow cytometrically in all but one patient. 99mTc-sestamibi enhancement was seen in the primary tumour and the bone marrow metastases of one of the ten patients, and this result was concordant with a negative Pgp status. The findings presented suggest that 99mTc-sestamibi imaging results might correlate with the presence of functional Pgp in neural crest tumours without MYCN amplification.

3-Iodobenzylguanidine↗

Normal appearances of technetium-99m dimercaptosuccinic acid in children on planar imaging.

Thirty-two children who underwent renal arteriography with normal results also underwent technetium-99m dimercaptosuccinic acid (DMSA) imaging. Variations in the normal appearance of 99mTc-DMSA images are described in these children. Criteria for high-quality 99mTc DMSA images are defined in terms of kidney outline and contrast between the inner and the outer part of the kidney. Most of the images in this study were of high quality. The two most common features of normal 99mTc-DMSA images were a round-shaped (50%) or flat (either lateral or medial aspect) (24.8%) contour. A small number of unusual appearances were observed and these have been illustrated. The mean differential function of the left kidney was 51% with a range of 45%-57%.

Child↗

Technetium-99m sestamibi single-photon emission tomography detects subclinical myocardial perfusion abnormalities in patients with systemic lupus erythematosus.

In patients with systemic lupus erythematosus, involvement of the cardiovascular system is the third leading cause of death. However, although autopsy studies have demonstrated a high incidence of abnormalities in both the myocardium and coronary vessels, clinical manifestations have been reported in only a small percentage of cases. The aim of this study was to evaluate myocardial perfusion in asymptomatic lupus patients using technetium-99m sestamibi single-photon emission tomography (SPET). Twenty-eight patients without overt cardiac involvement and risk factors were studied with 99mTc-sestamibi SPET at rest and after dipyridamole infusion. Perfusion abnormalities were detected in 18 cases: six had persistent defects, three had reversible defects, seven had both persistent and reversible defects, and two showed rest defects which normalized on dipyridamole images ("reverse redistribution pattern"). Coronary angiography was performed in eight patients with positive 99mTc-sestamibi SPET, and showed normal epicardial vessels in all the cases. These results indicate that 99mTc-sestamibi SPET reveals a high prevalence (18 out of 28 patients in this study, i.e. 64%) of myocardial perfusion abnormalities in asymptomatic lupus patients, probably due to the primary immunological damage of this autoimmune disease. In conclusion, rest/dipyridamole 99mTc-sestamibi SPET can be a useful non-invasive method to identify subclinical myocardial involvement in systemic lupus erythematosus, and patients potentially at risk of later cardiac events.

Adult↗

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the differential diagnosis of cold thyroid nodules.

Various diagnostic techniques have been successfully used in the clinical management of cold nodules; however, the decision on whether to employ surgery or a conservative treatment is not always easy. This study was designed to appraise the diagnostic value of technetium-99m methoxyisobutylisonitrile (MIBI) scintigraphy in the assessment of cold nodules detected using (99m)Tc-pertechnetate. Fifty-two patients were included in the study. All had already been selected for surgery, based on their clinical and laboratory findings, including fine-needle aspiration biopsy. The total number of cold nodules on (99m)Tc-pertechnetate scans was 59. The thyroid scan was performed 20-40 min after i.v. injection of 400 MBq of (99m)Tc-MIBI. Uptake of MIBI in thyroid nodules was compared with that in the surrounding normal thyroid tissue, and a score of between 0 and 3 was assigned to each nodule as follows: 0, cold; 1, decreased; 2, equal; 3, hot. Definitive histology revealed nodular goitre in 24 cases, adenoma in 19, thyroiditis in 1, differentiated cancer in 12, medullary cancer in 2, and anaplastic cancer in 1. None of the degenerative nodules were hot on MIBI scan, while the adenomas showed a variety of MIBI imaging patterns, most frequently the score 3 pattern. In the diagnosis of differentiated thyroid cancer the sensitivities of score 3 and score 2+3 MIBI uptake patterns were 83% (10/12) and 100%, respectively. The score 3 MIBI uptake pattern had a specificity of 100% and a positive predictive value of 100% with respect to thyroid (benign and malignant) neoplastic diseases, whereas a specificity of 72% and a positive predictive value of 43% were observed in the detection of differentiated cancer. After a cold nodule had been detected using (99m)Tc-pertechnetate, a second scan with high MIBI uptake increased by 7.8 times the probability that this nodule would be a differentiated cancer. In conclusion, (99m)Tc-MIBI scintigraphy is a useful method in the differential diagnosis of cold thyroid nodules if the primary aim is to differentiate degenerative from neoplastic diseases rather than to differentiate benign from malignant nodules. High MIBI uptake considerably increases the probability of a differentiated thyroid cancer and facilitates immediate surgical removal, while decreased uptake actually excludes it. We suggest a combination of fine-needle aspiration biopsy and MIBI scan as a routine diagnostic approach to cold thyroid nodules.

Biopsy, Needle↗

Technetium-99m somatostatin analogues: effect of labelling methods and peptide sequence.

In this paper the preclinical evaluation of the somatostatin analogue RC160 labelled with technetium-99m using bifunctional chelators (BFCs) based on the hydrazinonicotinamide (HYNIC) and N(3)S system is described and a comparison made with [Tyr(3)]-octreotide (TOC). Conjugates of both peptides with HYNIC, and of RC160 with benzoyl-MAG(3) and an N(3)S-adipate derivative were prepared and radiolabelling performed at high specific activities using tricine, tricine/nicotinic acid and ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligands for HYNIC conjugates. All conjugates and (99m)Tc-labelled peptides showed preserved binding affinity for the somatostatin receptor (IC50, Kd<5 nM). The biodistribution was markedly dependent on the BFC and co-ligand used, with the amidothiol ligands showing a greater degree of hepatobiliary clearance, the HYNIC/tricine complex higher blood levels and the HYNIC/EDDA complex the highest level of renal excretion and lowest blood levels. All peptide conjugates showed receptor-mediated uptake in tumour xenografts, but tumour uptake was significantly lower for the (99m)Tc-RC160 derivatives compared with (99m)Tc-EDDA/HYNIC-[Tyr(3)]-octreotide (0.2%-3.5%ID/g vs 9.7%ID/g) and correlated well with the reduced internalisation rate for RC160 derivatives. Our results show that the selection of the labelling approach as well as the right choice of the peptide structure are crucial for labelling peptides with (99m)Tc to achieve complexes with favourable biodistribution. Despite the relatively low tumour uptake compared with (99m)Tc-EDDA/HYNIC-[Tyr(3)]-octreotide, (99m)Tc-RC160 could play a role in imaging tumours that do not bind octreotide derivatives.

Animals↗

Scintigraphic detection of acute experimental endocarditis with the technetium-99m labelled glycoprotein IIb/IIIa receptor antagonist DMP444.

Bacterial endocarditis is an important clinical problem that may result in persistent bacteraemia and irreversible cardiac damage. Since endocarditis is characterized by aggregation of activated platelets, fibrin and bacteria, we studied DMP444, a technetium-99m labelled high-affinity antagonist of the GP IIb/IIIa receptor that is expressed on activated platelets. In seven Beagle dogs (11-15 kg), the left ventricle was catheterized via the right carotid artery. One hour later, 5x10(7) colony forming units of Staphylococcus aureus were injected intracardially. Half an hour later, the catheter was removed. Two extra dogs underwent a complete sham procedure. One day after the intervention, five infected and the two non-infected dogs were injected with 37 MBq/kg 99mTc-DMP444 and two infected dogs with 37 MBq/kg 99mTc-IgG (used as a non-specific control agent) and imaged up to 4 h after injection. Samples were obtained for tissue counting, microbiology and histology. From 1 to 2 h post injection onward, there was clear focal accumulation of DMP444 in the aortic valve region when endocarditis was present, and this accumulation increased with time. The non-infected and the 99mTc-IgG injected dogs showed only persisting blood pool activity without any focal abnormality. At 4 h post injection, the in vivo valve-to-blood pool ratios were 1.87+/-0.18 in endocarditis, 1.01+/-0.05 in non-infected controls and 1.09+/-0.02 in 99mTc-IgG injected dogs (P<0.05). It is concluded that targeting activated platelets with the 99mTc-labelled GP IIb/IIIa antagonist DMP444 allows a final diagnosis of experimental bacterial endocarditis within 4 h owing to high, specific and fast in vivo uptake.

Acute Disease↗

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

The aim of this study was to investigate the possible role of technetium-99m methoxyisobutylisonitrile (MIBI) scan in planning post-surgical therapy and follow-up in patients with differentiated thyroid carcinoma (DTC). Four groups of DTC patients were considered: Group 1 comprised 122 patients with high serum thyroglobulin (s-Tg) levels and negative high-dose iodine-131 scan during follow-up who had previously undergone total thyroidectomy and 131I treatment. Group 2 consisted of 27 patients who had previously undergone total thyroidectomy and 131I treatment but were now considered disease-free; this group was considered as controls. Group 3 comprised 49 patients studied after total thyroidectomy but prior to 131I scan. Finally, group 4 consisted of 21 patients who had previously undergone partial thyroidectomy alone. MIBI scan, neck ultrasonography (US), and s-Tg measurements during suppressive hormonal therapy (SHT) were obtained in all patients. Neck and chest computed tomography (CT) or magnetic resonance imaging (MRI) was also performed in group 1 patients. In group 1, MIBI scan and US were very sensitive in detecting cervical lymph node metastases (93.54% and 89.24%, respectively). Furthermore, MIBI scan and US played a complementary role in several patients, yielding a global sensitivity of 97.84%. In contrast, CT/MRI sensitivity for cervical lymph node metastases was very low (43.01%). MIBI scan also showed a higher sensitivity than CT/MRI in detecting mediastinal lymph node metastases (100% vs 57.89%). Regarding distant metastases, MIBI scan provided results similar to those of conventional imaging (CT, MRI, 99mTc-methylene diphosphonate bone scan). In group 2, no false-positive cases were observed with MIBI scan (100% specificity). In group 3, MIBI scan correctly identified all the 131I-positive metastatic foci, except in two patients with micronodular pulmonary metastases that were visualised with 131I scan. In contrast, both MIBI scan and US showed low sensitivity (46.15% and 61.53%, respectively) compared with 131I scan in detecting thyroid remnants. s-Tg was increased in all patients with distant metastases but only in 56% of those with lymph node metastases. Furthermore, s-Tg was increased in 21.42% of patients with thyroid remnants alone (false-positive results). In group 4, MIBI scan was the only examination capable of detecting at an early stage a mediastinal lymph node metastasis in one patient. We conclude that the integrated MIBI scan/neck US protocol: (a) can be proposed as a first-line diagnostic procedure in the follow-up of DTC patients with high s-Tg levels and negative high-dose 131I scan, and (b) may be helpful in the follow-up of DTC patients who undergo partial thyroidectomy alone. Moreover, the combined MIBI scan/neck US/s-Tg protocol appears to be highly sensitive in identifying patients with metastatic disease after total thyroidectomy and prior to 1311 scan; consequently, it may play a prognostic role in distinguishing high-risk from low-risk DTC patients. However, due to the low sensitivity of MIBI scan and neck US in detecting thyroid remnants, this diagnostic approach cannot be used as a predictor of 131I scan results. Lastly, because of the high sensitivity of MIBI scan and neck US in revealing both functioning and non-functioning metastases, this integrated protocol might be helpful in the follow-up of high-risk DTC patients, particularly for the early detection of lymph node metastases in patients with undetectable s-Tg during SHT.

Aged↗

Iterative reconstruction: an improvement of technetium-99m MIBI SPET for the detection of parathyroid adenomas?

The purpose of this study was to assess the value of technetium-99m methoxyisobutylisonitrile (MIBI) single-photon emission tomography (SPET) and an iterative reconstruction algorithm for the preoperative localisation of parathyroid adenomas (PTAs). Seventy-two patients (26 male, 46 female, mean age 58+/-16 years) with known primary hyperparathyroidism were examined preoperatively. First, a thyroid examination was performed to detect possible MIBI-accumulating thyroid lesions. Planar scans were then acquired 15 and 120 min and tomographic images 120 min after intravenous injection of 740 MBq 99mTc-MIBI, using a triple-head gamma camera (Picker Prism 3000). Additionally, 99mTc-MIBI/ 99mTc-pertechnetate subtraction scintigraphy of the early planar images was performed. The SPET data were evaluated using an iterative reconstruction (multiplicative iterative SPET reconstruction: MISR) as well as a standard algorithm (FBP: filtered back-projection with application of a 3-D low-pass postfilter). The weight of the resected PTAs ranged from 110 mg to 5 g. Using planar MIBI scans, correct localisation of the side of the PTA was possible in 81% of cases (58% for PTAs weighing less than 500 mg). Sensitivity increased to 94% using SPET and FBP, while with MISR it rose further, to 97%. Patients with PTAs weighing less than 500 mg showed a sensitivity of 88% with MISR and 81% with FBP. Furthermore, there was a clear improvement in image quality using MISR. None of the normal parathyroid glands were visualised. This study indicates that, in comparison with planar scintigraphy, 99mTc-MIBI SPET is a more sensitive and specific tool for topographical localisation of PTAs, especially those that are small. There is a further improvement in sensitivity and image quality when iterative reconstruction is used instead of FBP.

Adenoma↗

The effect of collateral flow and myocardial viability on the distribution of technetium-99m sestamibi in a closed-chest model of coronary occlusion and reperfusion.

Myocardial uptake of technetium-99m sestamibi at low coronary flow rates overestimates blood flow, but the relative impact of flow and viability on 99mTc-sestamibi kinetics is unclear. The objective of this study was to determine the effect of myocardial viability and the degree of collateral blood flow on the uptake and retention of 99mTc-sestamibi by examining three animal models of coronary occlusion and reperfusion, each reflecting a different state of viability and collateral blood flow. Three closed-chest animal models were studied: canine (high collateral flow, preserved viability), porcine (low collateral flow, absent viability) and porcine with slowly occlusive coronary stents producing infarction and enhanced collateral blood flow (high collateral flow, absent viability). There were seven dogs, seven pigs and six pigs, respectively, in each animal model. Animals from all three models were subjected to a 40-min total left anterior descending artery (LAD) occlusion followed by 2 h of reperfusion. 99mTc-sestamibi and radiolabelled microspheres were injected during LAD occlusion 10 min prior to reperfusion. Animals were sacrificed after 2 h of reperfusion flow. Ex situ heart slice imaging to determine risk area was followed by viability staining to determine infarct size. Slices were subsequently sectioned into equally sized radial segments and placed in a gamma well counter. Risk area as determined by ex situ 99mTc-sestamibi imaging was not significantly different by model. Pathological infarct size differed significantly by model [canine = 1%+/-1% of the left ventricle (LV); porcine = 13%+/-8% LV; porcine with stent = 14%+/-7% LV; P = 0.002)]. Collateral blood flow by microspheres during occlusion tended to differ among models (overall P = 0.08), with the canine and porcine with stent models having relatively high flow rates compared with the acute porcine model. 99mTc-sestamibi activity correlated with microsphere blood flow in all three models, with r values for individual animals (n = 20) ranging from 0.86 to 0.96 (all P<0.0001). There was a significant difference in the regression line intercepts (P<0.0001) and slopes (P<0.01) among the three models comparing 99mTc-sestamibi uptake with myocardial blood flow. 99mTc-sestamibi uptake overestimated blood flow to a greater extent in the canine model (high flow with viability) than in the porcine model (low flow, absent viability). Despite enhanced collateral flow, there was significantly less overestimation of flow in the porcine stent model (high flow, absent viability). In conclusion, at low flow rates 99mTc-sestamibi activity overestimates myocardial blood flow. This effect is most pronounced in myocardium with significant collateral flow and preserved viability, consistent with over-extraction or redistribution of the tracer. The effect is markedly decreased in non-viable myocardium regardless of blood flow.

Animals↗