Minimally invasive parathyroid carcinoma-A missing entity between parathyroid adenoma and carcinoma: Scintigraphic and histological features.

PURPOSE: Minimally invasive parathyroid carcinoma (MIPC) is clinically and biochemically comparable with parathyroid adenoma (PA) though histopathologically differ from PA. MIPC is an intermediate of PA and parathyroid carcinoma (PC). In literature, there is no definite criterion to diagnose MIPC. Our aim was to evaluate and characterize the imaging and biochemical parameters with histological characteristics of MIPC. METHODOLOGY: Ten patients with MIPC were recruited from (single centre) Indian PHPT registry (www.indianphptregistry.com) from January 2014 to July 2018. Clinical, biochemical, imaging and histological features of MIPC patients were reviewed. RESULTS: The mean age of MIPC patients (n = 10; 3 males) was 39.9 ± 11.3 years (range: 17-50). All patients had an elevated preoperative parathyroid hormone (iPTH) level ranging from 427 to 2138 pg/mL (median: 1328). MIBI scan showed intensely avid and enlarged parathyroid tumours in all patients; LIPT in 6, RIPT in 3 and ectopic mediastinal in 1 with mean size of the tumours was 2.8 ± 1.1 cm. The mean of maximum standardized uptake value (SUVmax) of MIPC in F-18 fluorocholine PET/CT was 6.7 ± 1.1 (range 6.0-8.3). The mean tumour weight was 12 ± 9.5 g (range: 1.09-28). All MIPC patients had identified capsular invasion in 80% and vascular invasion in 50% only but there was no local invasion, lymph nodal or distant metastasis. The mean Ki-67 labelling index was 3.2 ± 2.7 (range 1.1-10). CONCLUSION: The study concluded that MIPC patients are less aggressive (on the basis of imaging and histopathological findings) and should be differentiated from parathyroid adenoma and carcinoma.

Development of a rapid HPLC method for quantification of the copper tetramibi tetraflourborate in a kit for preparation of Technetium 99 m Sestamibi Injection.

Radiopharmaceuticals are radioactive compounds that can be used for diagnostic and therapeutic purposes. Technetium (99mTc) Sestamibi is the most commercialized radiopharmaceutical in the world. It includes a coordination complex consisting of the radioisotope 99 m technetium bound to six copper tetramibi tetrafluorborate ligands, and is mainly used to image the myocardium via scintigraphy. As radiopharmaceuticals are regarded as drugs, they are subject to the same regulations; therefore, the objective of this study was to develop a quantification method for the active pharmaceutical ingredient before their complexation with the radioisotope by employing high-performance liquid chromatography (HPLC) methodology. A simple and efficient method (retention time = 2.5 min) was developed and validated for copper tetramibi tetrafluorborate in the final product using a buffer and organic solvent mixtures (ACN-methanol-ammonium sulfate buffer) and a C18 column. The analytical protocol was fast, taking around 30 min until evaluation of results. The validation parameters were evaluated with satisfactory results: in terms of linearity r > 0.99 (160-240 µg/mL) and no deviation was observed. The RSD of precision was <5%, and an average recovery of 99% was observed for accuracy. The proposed method was thus considered adequate for routine analysis in the pharmaceutical industries.

Incidental meningioma detected by using 99mTc-MIBI SPECT/CT / Detección incidental de meningioma con 99mTc-MIBI SPECT/TC

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Adenoma quístico paratiroideo: hiperparatiroidismo primario sin captación de 99mTc-MIBI / Cystic parathyroid adenoma: primary hyperparathyroidism without 99mTc-MIBI uptake

El adenoma quístico paratiroideo es una entidad poco frecuente (<0,01% de las masas cervicales) que cursa con hiperparatiroidismo primario en un 9% de los casos. La gammagrafía de paratiroides es fundamental para su diagnóstico y no es frecuente un resultado falso negativo. El uso de equipos híbridos SPECT/TC permite establecer un diagnóstico de localización más preciso. El tratamiento en casos funcionales es finalmente quirúrgico. Se presenta el caso de una mujer de 64 años diagnosticada de hiperparatiroidismo con adenoma quístico paratiroideo y gammagrafía negativa (AU)

Cystic parathyroid adenoma is a rare disease (<0.01% of all cervical masses) that associates primary hyperparathyroidism in 9% of cases. Parathyroid scintigraphy is essential for its diagnosis with uncommon false negative results. Hybrid SPECT/CT equipments allow a more accurate diagnosis. Functional cystic parathyroid adenomas are surgically treated. A case of a 64-year-old woman with diagnoses of hyperparathyroidism and a cystic parathyroid adenoma without uptake in scintigraphy is described (AU)

Primary hyperparathyroidism regression associated to cinacalcet therapy proved by 99mTc-MIBI scintigraphy / Seguimiento mediante gammagrafía con 99mTc-MIBI en un caso de hiperparatiroidismo primario tratado con cinacalcet

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Un caso infrecuente de doble adenoma paratiroideo evidenciado con 99mTc-sestaMIBI SPECT/TC / A rare case of double parathyroid adenoma evidenced by 99mTc-sestaMIBI SPECT/CT

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Contribution of early SPECT/CT to 99mTc-MIBI double phase scintigraphy in primary hyperparathyroidism: Diagnostic value and correlation between uptake and biological parameters / Aportación del SPECT/TC precoz a la gammagrafía de doble fase con 99mTc-MIBI en pacientes con hiperparatiroidismo primario: valor diagnóstico y correlación de la captación con parámetros biológicos

Aim. To evaluate the value of 99mTc-MIBI double-phase scintigraphy (DPS) and early SPECT/CT in the pre-surgical assessment of patients with primary hyperparathyroidism (PHPT). Also, to calculate the correlation between uptake and some biological parameters. Material and methods. Forty patients with PHPT were included: 37 solitary adenomas, 1 hyperplasia, and 2 double adenomas. Fifteen patients had ectopic glands. DPS and early SPECT/CT were acquired in all patients. Ultrasound was performed in 31/40. All patients underwent surgery, intra-operative iPTH measurements, and histopathological examinations. Qualitative DPS uptake was assessed and correlated to pre-surgical calcium, iPTH levels, gland weight, and maximum diameter. Results. In the planar study, there were 23 positive cases, 8 doubtful, and 9 negatives. With the SPECT/CT, 8/9 negatives cases were located. All doubtful cases were confirmed as positives. Gland location improved in 16 cases (12 ectopic). DPS+SPECT/CT failed to detect a solitary adenoma and at least one gland in three cases of multiglandular disease (MGD). The sensitivity by patient was: DPS 72.5%, DPS+SPECT/CT 90%, and ultrasound 42%. Ultrasound and scintigraphy (DPS+SPECT/CT) were concordant in 16/31 patients. For the rest of them, scintigraphy proved correct in 14/15, and both techniques failed in one case. There was a significant correlation between level of uptake and iPTH level, gland weight, and maximum diameter. Conclusion. Early SPECT/CT improves sensitivity and the locating of parathyroid pathological glands and increases diagnostic confidence. iPTH level, glandular size, and weight are related to the qualitative assessment of 99mTc-MIBI uptake in early DPS (AU)

Objetivo. Evaluar la gammagrafía de doble fase con 99mTc-MIBI (GDF) y el SPECT/TC precoz, en la valoración prequirúrgica del hiperparatiroidismo primario (HPTP), calculando la correlación entre grado de captación y algunos parámetros biológicos. Material y métodos. Se incluyeron 40 pacientes: 37 adenomas solitarios, dos adenomas dobles, una hiperplasia. Quince tenían glándulas ectópicas. En 40 pacientes se realizaron GDF y SPECT/TC; en 31/40, ecografía. Todos los pacientes fueron intervenidos, realizando determinación de PTHi intraoperatoria y examen histopatológico. Se evaluó cualitativamente la captación en la GDF, correlacionándose con calcio y PTHi prequirúrgicos, peso y diámetro máximo glandulares. Resultados. En el estudio planar se obtuvieron 23 casos positivos, 8 dudosos, y 9 negativos. Con SPECT/TC se localizaron 8/9 de los negativos. Todos los dudosos se confirmaron como positivos. La localización glandular mejoró en 16 casos (12 ectópicos). La GDF+SPECT/TC fallaron en la detección de un adenoma solitario y en la visualización de alguna de las glándulas en tres casos de enfermedad multiglandular (EMG). La sensibilidad por pacientes fue: GDF 72,5%, GDF+SPECT/TC 90%, ecografía 42%. Ecografía y gammagrafía (GDF+SPECT/TC) concordaron en 16/31 pacientes. De los no concordantes, la gammagrafía acertó en 14/15 y ambas técnicas fallaron en uno. Hubo correlación significativa entre captación y PTHi, peso y diámetro máximo glandulares. Conclusion. El SPECT/TC precoz mejora la sensibilidad y la localización de las paratiroides patológicas y aumenta la confianza diagnóstica. PTHi, tamaño y peso glandulares se correlacionan con la valoración cualitativa de la captación precoz de 99mTc-MIBI en la GDF (AU)

An unusual presentation of primary hyperparathyroidism: multiple brown tumors and coexisting thyroid carcinoma / Presentación inusual de hiperparatiroidismo primario: múltiples tumores pardos y coexistencia de carcinoma tiroideo

We present a patient with a complex clinical picture of primary hyperparathyroidism with multiple destructive skeletal lesions suspicious of bone metastases and concomitant multifocal papillary thyroid carcinoma with a metastatic central lymph node. He presented with progressively worsening right hip pain and restricted motion. Magnetic resonance imaging revealed multiple lytic lesions involving predominantly the right trochanter minor and the left inferior and posterior pubic rami. Biochemical tests were consistent with primary hyperparathyroidism. Neck ultrasound and parathyroid scintigraphy revealed a single parathyroid adenoma and a thyroid nodule, preoperative cytology of which confirmed papillary thyroid carcinoma, as did the final surgical specimen. Biochemical results, regarding hyperparathyroidism, declined to normal levels and his complaints gradually decreased after surgery. Postoperative whole body bone scintigraphy showed increased tracer uptakes at multiple sites, but they were proved to be metabolically inactive by fluorodeoxyglucose positron emission tomography/computed tomography (AU)

Presentamos el caso de un paciente con un cuadro clínico de hiperparatiroidismo primario, con muchas lesiones óseas destructivas sospechosas de metástasis óseas y carcinoma tiroideo multifocal concomitante con un ganglio linfático metastásico central. Se presentó con agravamiento progresivo de dolor y restricción de movimiento en la cadera derecha. La resonancia magnética reveló múltiples lesiones líticas que implicaban principalmente al trocánter menor derecho y a las ramas púbicas izquierdas inferior y posterior. Las pruebas bioquímicas fueron consistentes con un hiperparatiroidismo primario. La ecografía cervical y la gammagrafía paratiroidea revelaron un único adenoma paratiroideo y un nódulo tiroideo, cuya citología preoperatoria confirmó un carcinoma papilar de tiroides, que fue confirmado también por la muestra final obtenida quirúrgicamente. Los resultados bioquímicos, en relación con el hiperparatiroidismo, descendieron a niveles normales tras la cirugía, y los dolores fueron remitiendo gradualmente. La gammagrafía ósea postoperatoria de cuerpo entero reflejó un incremento de captación del radiotrazador en múltiples localizaciones, que resultaron ser metabólicamente inactivas en la tomografía por emisión de positrones con fluorodesoxiglucosa/tomografía computarizada (AU)

Pronounced alterations in T-wave morphology during dipyridamole-induced ischaemia.

The case describes a 77-year-old woman with multivessel coronary disease exhibiting marked changes of T-wave morphology induced by dipyridamole, an unusual finding in which the diagnostic accuracy in this clinical context is uncertain. Gated-SPECT imaging demonstrated severe ischaemia extending through inferior and posterolateral regions of the left ventricle with normal motility and contractile function in response to vasodilator stress. Possible underlying mechanisms and clinical implications of observed electrocardiographic changes are discussed. T-loop modifications during vasodilator stress SPECT and correlation of these changes with the amount of ischaemic injury need further evaluation.

Unusual ¹8F-FDG PET/CT finding of an oxyphil parathyroid adenoma in a patient with Hodgkin's Lymphoma.

Malignancy-associated hypercalcemia is a complication of advanced tumours that is associated to a poor prognosis. Thorough evaluation to establish its cause is essential because some patients may actually have undiagnosed primary hyperparathyroidism. We report a case of a patient affected by Hodgkin's Lymphoma and persistent hypercalcemia with an incidental (18)F-FDG PET/CT finding in the anterior neck region, not ascribable to malignancy, confirmed with (99m)Tc-sestamibi scintigraphy. It was removed by minimally invasive surgery. It was shown to be an oxyphil parathyroid adenoma localized in an unusual site.

Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera.

PURPOSE: Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. METHODS: Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with (201)Tl (84 patients) or (99m)Tc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for (201)Tl (78 patients) or (99m)Tc-sestamibi (80 patients) exercise CZT SPECT. RESULTS: The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for (201)Tl than for (99m)Tc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26% error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for (99m)Tc-sestamibi and 30.5 and 13.1ppm for (201)Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for (99m)Tc-sestamibi and 39 and 91 MBq for (201)Tl, respectively. CONCLUSION: Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for (99m)Tc-sestamibi and in non-obese subjects.

Myocardial 99mTc-sestamibi extraction and washout in hypertensive heart failure using an isolated rat heart.

PURPOSE: Myocardial mitochondria are the primary part of energy production for healthy cardiac contraction. And mitochondrial dysfunction would play an important role in progressive heart failure. In the recent years, myocardial washout of (99m)Tc-sestamibi [((99m)Tc-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI)] has been introduced to be a potential marker in patients with heart failure. The objective of this study was to clarify MIBI extraction and washout kinetics using isolated perfusion system in hypertension induced model of myocardial dysfunction. METHODS: Six-week-old Dahl-salt sensitive rats, allotted to 4 groups; a 5-week high-salt group (5 wk-HS), 12-week high-salt group (12 wk-HS) and two age-matched, low-salt diet control groups (5 wk-LS and 12 wk-LS). The rats in 5 wk-HS and 12 wk-HS groups were fed a high-salt diet (containing 8% NaCl). Cardiac function was examined by echocardiography before removing heart. Hearts were perfused according to the Langendorff method at a constant flow rate, in which 20-min MIBI washin was conducted followed by 25-min MIBI washout. Whole heart radioactivity was collected every sec by an external gamma detector. The myocardial extraction, K(1) (ml/min) and washout rate, k(2) (min(-1)) were generated. RESULTS: High-salt diet groups showed significant high-blood pressure. Echocardiography revealed thickened LV walls in 5 wk-HS, and reduced cardiac function in 12 wk-HS, compared to each age-matched control group. K(1) showed no significant difference among all groups (5 wk-HS: 2.36 ± 1.07, 5 wk-control: 2.59 ± 0.28, 12 wk-HS: 1.91 ± 0.90, and 12 wk-control: 2.84 ± 0.57). k(2) in 5 wk-HS was comparable to that in the age matched control group (0.00030 ± 0.00039 vs -0.000010 ± 0.00044), but it was increased remarkably in 18 wk-HS compared to the age matched control group (0.0025 ± 0.0011 vs 0.000025 ± 0.000041, P<.01), and 5 wk-HS (P<.01). CONCLUSION: In the course of hypertensive heart disease, MIBI washout was increased in the transitional state from hypertrophied to dilated and failing heart, while MIBI extraction remained intact.

The effect on radiochemical purity of modifications to the method of preparation and dilution of 99mTc-sestamibi.

BACKGROUND: 99mTc-sestamibi is a useful radiopharmaceutical for myocardial perfusion imaging, parathyroid imaging and breast tumour imaging. However, the preparation is time consuming and the limit of 3 ml on the volume of liquid that can be added to the Cardiolite kit vial means that it is often difficult to draw up small doses for patient studies. AIM: To modify the method of preparation of 99mTc-sestamibi in order to reduce the preparation time and to give a preparation which is more convenient for withdrawing patient doses. METHOD: A modified kit was prepared by reconstituting a Cardiolite kit vial with 3 ml Sodium Chloride Injection (0.9%) BP, sub-dividing it into two separate nitrogen-filled vials before adding sodium pertechnetate and boiling for radiolabelling. 99mTc-sestamibi was also prepared according to the manufacturer's recommended method and diluted with sodium chloride injection after preparation. Radiochemical purity was assessed by thin-layer chromatography and high-performance liquid chromatography. RESULTS: 99mTc-sestamibi prepared according to the manufacturer's recommended method had high radiochemical purity (96.9%+/-1.1%) and retained >90% radiochemical purity over 8 h following dilution. However, 99mTc-sestamibi prepared by the modified method gave variable and inconsistent results. CONCLUSION: The modified method of preparation was not robust enough to give reproducibly high radiochemical purity. However, dilution of 99mTc-sestamibi prepared according to the manufacturer's recommended method was satisfactory. This study highlights problems with the analysis of 99mTc-sestamibi and the limitations of modifying the method of preparation.

Increasing the radiochemical purity of 99mTc sestamibi commercial preparations results in improved sensitivity of dual-phase planar parathyroid scintigraphy.

BACKGROUND: Poor results for dual-phase parathyroid scintigraphy have recently prompted increased use of dual-tracer imaging. We noticed that seminal studies used higher radiochemical purity than provided by current commercial preparations meeting US Pharmacopea (USP) specifications (90% of technetium bound to sestamibi). We surmised that the presence of unbound Tc (non-MIBI tracer) might hamper dual-phase detection that is dependent on rapid wash-out of technetium from thyroid tissue. PURPOSE: To test the hypothesis that reducing non-MIBI tracer will enhance thyroid wash-out and improve sensitivity of dual-phase imaging. METHODS: Starting in April 2003 we decreased the technetium to sestamibi ratio. This resulted in a significant decrease of non-MIBI tracer from 8.1+/-2.2% (SD) (group 1, n = 42) to 3.5+/-1.1% (group 2, n = 47) (P < 0.05 t-test). We performed a retrospective review of 89 patients with primary hyperparathyroidism who underwent imaging and subsequent surgery. The pathological findings served as the 'gold standard'. RESULTS: Scanning detected 21/39 diseased glands (sensitivity=54%) in group 1 patients. In group 2 imaging detected 38/45 diseased glands (sensitivity = 84%). An improvement in sensitivity (P < 0.01) was achieved by modifying the radiopharmaceutical preparation. CONCLUSIONS: Elevated levels of non-MIBI tracer in Tc-MIBI commercial preparations result in persistent thyroid background activity that may interfere with detection of parathyroid pathology. Achieving a higher degree of radiochemical purity (at least 95% bound, 5% impurities) than required by USP may be needed for optimal results. The large variation in sensitivity reported in the literature may be related in part to non-uniform radiopharmaceutical preparation.

Imaging multidrug resistance P-glycoprotein transport function using microPET with technetium-94m-sestamibi.

The best characterized mechanism of multidrug resistance (MDR) in cancer involves the MDR1 efflux transporter P-glycoprotein (Pgp). The positron-emitting radiotracer hexakis(2-methoxyisobutylisonitrile)-(94m)Tc ((94m)Tc-MIBI) was synthesized and validated in cell transport studies as a substrate for MDR1 Pgp. In vivo small-scale PET imaging and biodistribution studies of mdr1a/1b (-/-) gene deleted and wild-type mice demonstrated the use of (94m)Tc-MIBI to detect Pgp function. The reversal effect of a Pgp modulator was shown in tissue distribution studies of KB 3-1 (Pgp-) and KB 8-5 (Pgp+) tumor-bearing nude mice. The current (94m)Tc-MIBI experiments parallel previous studies employing (99m)Tc-MIBI, showing essentially identical performance of the two technetium radiotracers and providing biological validation of (94m)Tc-MIBI for PET imaging of multidrug resistance.

The effect of selected preparation variables on the radiochemical purity of 99mTc-sestamibi.

OBJECTIVE: Measurement of cardiac perfusion via agents such as 99mTc-sestamibi (Cardiolite; DuPont-Merck Pharmaceutical Co., Inc.) is widely used in clinical nuclear medicine for the diagnosis of coronary artery disease. The monograph for 99mTc-sestamibi recommends at least 90% radiochemical purity (RCP) for clinical use. Various factors may influence the RCP of certain reagent kits. Some of these include the amount of activity added to the reagent kit, the generator ingrowth time, the generator manufacturer, the age of the eluate, and the age of the formulated kit. A D-optimal design with a 20-experiment run was devised to study the effects of these variables either alone or in combination on the RCP of 99mTc-sestamibi. METHODS: The RCP was assessed by Baker-Flex thin-layer and high-performance liquid chromatographic methods, immediately and 6 h after reconstitution of the 99mTc-sestamibi. RESULTS: The results showed that 4 of the 5 variables studied were statistically significant predictors of the RCP. The age of the formulated kit did not influence the RCP. CONCLUSION: For any combination of these 4 variables, the mean RCP remained greater than or equal to 90%, that is, within the recommended range of RCP for clinical use at radioactivity levels ranging from 5,550 MBq to 37,000 MBq.

Identity confirmation of 99mTc-MAG3, 99mTc-sestamibi and 99mTc-ECD using radio-LC-MS.

Due to the low concentrations in which 99mTc-radiopharmaceuticals are obtained (4-40 ng/ml), confirmation of the identity of these tracer agents in the European Pharmacopoeia is generally performed only indirectly by assessment of their retention times on RP-HPLC. We have investigated whether it is possible to obtain more direct proof of the identity of technetium-99m labelled radiopharmaceuticals using radio-LC-MS. As representative examples, negatively charged 99mTc-MAG3, positively charged 99mTc-Sestamibi and neutral 99mTc-ECD were used. The three technetium-99m radiopharmaceuticals were prepared in several conditions to obtain variable relative amounts of radiochemical impurities and variable concentrations of the complexes (pico- to nanomolar). The preparations were analyzed on a reversed phase C18 HPLC column using a radio-LC-MS system equipped with a time of flight mass spectrometer with electrospray ionization in positive (99mTc-Sestamibi, 99mTc-ECD) or negative (99mTc-MAG3, 99mTc-ECD) mode. For each of the studied complexes, the main peak in the radiometric channel coincided with the expected molecular ion mass of the corresponding technetium complex in the mass spectrometer channel. The relative error on the measured accurate mass was in the range of 10 ppm. The identity of several radiochemical impurities of the three technetium complexes was also confirmed or established. It is concluded that radio-LC-MS can be a sensitive aid in quality control of 'no carrier added' radiopharmaceuticals.