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Mutual contribution by "track" microradioautography method (MRA) and secondary ion mass spectrometry (SIMS) microscopy: prospects in technetium dosimetry at-the cellular level.

The determination of cellular uptake sites of radioligands used for cell labelling for diagnostic purposes is an essential prerequisite for evaluating the radiation dose to the cell nucleus and cytoplasm. The distribution of 99mTc-HMPAO in labelled leukocytes was studied by two microscopic imaging techniques on the same biological material: the "track" microradioautographic method (MRA) and Secondary Ion Mass Spectrometry (SIMS) microscopy. The "track" method used internal conversion electrons of 99mTc, leading to the formation of silver grains in a thick layer nuclear emulsion deposited onto cellular smear. In order to improve the specificity of the "track" detection, a minimum of 5 consecutive silver grains was required. In SIMS Microscopy, mapping with 99Tc "daughter" nuclide of 99mTc (half-life: 2.13.10(5) years) was obtained after sputtering of superficial molecular layers on embedded specimen sections. A mass resolution of about 5,000 was needed to circumvent polyatomic ion interferences. Both methods were able to demonstrate a very heterogeneous distribution of technetium from one cell to another. The sensitivity and signal/noise ratios were excellent for both methods. The lateral resolution of SIMS microscopy (0.5 microns) was far better than that of MRA. Therefore, only SIMS is able to distinguish between nuclear and cytoplasmic localization. On the other hand, quantification was not achieved for SIMS, although semi-quantification is possible with MRA. The field of view of MRA is far larger, allowing a better statistical approach for quantification. Both methods appear to be complementary to determine the distribution of technetium at the cell level. MRA is simpler and better fitted to the study of a cell population or a tissue. The unique spatial resolution of SIMS allows to focus the study on subcellular structures.

Autoradiography↗

Technetium-99m-DTPA-galactosyl human serum albumin liver scintigraphy evaluation of regional CT/MRI attenuation/signal intensity differences.

UNLABELLED: Regional attenuation/signal intensity differences seen on CT/magnetic resonance imaging can be a clue in detecting regional hepatic blood flow abnormality. Sometimes, however, they can be misinterpreted as a hepatic neoplasm or, in the case of a true neoplasm, they can lead to an overestimation of its size because these regions often have similar attenuation or signal intensity to hepatic neoplasms. We evaluated 99mTc-diethylenetriaminepentaacetic acid-galactosyl human serum albumin (99mTc-DTPA-GSA) liver scintigrams in patients manifesting regional attenuation/signal intensity differences to further analyze the findings. METHODS: Technetium-99m-DTPA-GSA scintigrams of 23 patients with regional attenuation/signal intensity differences in the liver at dynamic contrast-enhanced CT/magnetic resonance imaging were evaluated. The causes of the differences were arterioportal (AP) shunts in seven patients, decreases in the portal venous flow in seven patients, occlusion of right hepatic vein in one patient, confluent hepatic fibrosis in one patient and unknown in seven patients. The accumulation of 99mTc-DTPA-GSA was compared with each known cause of attenuation/signal intensity difference. Count ratios of the regions to normal hepatic parenchyma also were calculated in all cases. RESULTS: In AP shunts, none of seven patients showed any decreased accumulation in the region. Accumulation of 99mTc-DTPA-GSA decreased in six of seven patients who had decreases in portal venous flow; this incidence was significantly higher than that in patients who had AP shunts (p < 0.005). In cases of unknown cause, two of seven patients showed a decrease in accumulation, but the other five showed no such decrease. The one patient with occlusion of the right hepatic vein showed no decrease, but the confluent hepatic fibrosis showed a significant decrease. The count ratio in AP shunts was significantly larger than that of the decrease in the portal venous flow (p < 0.005). CONCLUSION: Technetium-99m-DTPA-GSA accumulation in AP shunts has a different pattern from that found in patients with a decrease in portal venous flow. Therefore, differentiation between AP shunts, which showed no decrease in 99mTc-DTPA-GSA accumulation, and hepatic neoplasms can be made more easily.

Carcinoma, Hepatocellular↗

Occult osseous metastasis of a colonic adenocarcinoma visualized with technetium tc 99m hydroxymethylene diphosphate scintigraphy in a horse.

A 5-year-old Arabian horse was admitted with a 5-day history of undulant pyrexia of unknown origin, inappetence, obtundation, and acute collapse. Physical examination results were unremarkable except for a grade II/VI left-sided systolic cardiac murmur and abdominal splinting. Mild chronic inflammatory changes were evident on clinicopathologic evaluation. Echocardiography revealed moderate aortic insufficiency. A solitary soft tissue opacity was found on thoracic radiography but not on ultrasonography. Palliative treatment was ineffective. Nuclear scintigraphy with WBC labeled with technetium Tc 99m hexamethylpropyleneamine oxime did not identify abnormalities, but a second nuclear scan with technetium Tc 99m hydroxymethylene diphosphate identified polyostotic disease. Examination of a biopsy specimen from an affected rib revealed disseminated adenocarcinoma. The horse was euthanatized. Necropsy and histologic examination revealed a colonic adenocarcinoma with osseous metaplasia that had disseminated to multiple parenchymal organs, muscle, and bone.

Adenocarcinoma↗

Thallium-technetium parathyroid scan. A useful noninvasive technique for localization of abnormal parathyroid tissue.

We studied the usefulness of the thallium-technetium scan in 60 patients with suspected parathyroid disorders. The scan correctly localized abnormal parathyroid tissue in 82% of patients with surgically proved primary hyperparathyroidism due to a single adenoma and in 60% of patients operated on for primary hyperplasia. The scan was particularly useful in patients who had undergone previous neck explorations, since it successfully identified residual adenomatous or hyperplastic tissue in six of seven patients. False-positive images were consistently produced in all patients with coexisting thyroid disease. We conclude that the thallium-technetium scan is useful for localizing abnormal parathyroid tissue. We recommend its routine use in patients with persistent or recurrent hypercalcemia following neck exploration for primary hyperparathyroidism who have no evidence of thyroid disorders.

Adenoma↗

Clinicopathological correlation of technetium bone scan in vascularization of hydroxyapatite implants. A primate model.

OBJECTIVES: To report the histopathological and bone scan characteristics of the stages of hydroxyapatite fibrovascular integration and to consider the implications for the timing of peg drilling in a primate model. DESIGN: Three monkeys received hydroxyapatite implants covered only anteriorly with a fascia lata button to which the rectus muscles were sutured. Weekly bone scans were evaluated quantitatively and qualitatively. The orbits were harvested at 2, 4, and 8 weeks and examined histopathologically. RESULTS: Quantitatively, the implant's technetium uptake increased, then reached a plateau by 4 weeks. Peripheral uptake was present on the images and histologically at 2 weeks. When bone scan images suggested complete vascularization by the fourth week, the implant was 99% vascularized histologically. Completion of vascularization was ascertained at 8 weeks, without further discernible changes in the bone scans. CONCLUSIONS: The technetium bone scan is sensitive to the vascularization of the hydroxyapatite implant and discerns when complete vascularization is approached. This primate study models closely the clinical findings we have recently reported. We advocate at least a 4-week interval between the time the bone scan suggests full vascularization and peg drilling.

Animals↗

'Normal' technetium bone scans in patients with acute osteomyelitis.

Several investigators have stressed the usefulness of the technetium bone scan in the early diagnosis of acute osteomyelitis. Seven patients with acute osteomyelitis had initial bone scans that were reportedly normal. The diagnosis was made as a result of either an abnormal gallium scan, positive cultures, or changes in follow-up roentgenograms. The explanation for the normal technetium scans is conjectural but may be related to compromised vascularity. A normal scan does not rule out acute osteomyelitis. If this diagnosis is strongly suspected, other diagnostic tests should be used.

Acute Disease↗

Appearance of ectopic undescended inferior parathyroid adenomas on technetium Tc 99m sestamibi scintigraphy: a lesson from reoperative parathyroidectomy.

HYPOTHESIS: Critical postoperative review of technetium Tc 99m sestamibi scintigraphy can identify an undescended parathyroid adenoma on scans initially interpreted as nondiagnostic or negative. DESIGN: Case series. SETTING: A single, tertiary care academic medical center. PATIENTS: Three patients with persistent hyperparathyroidism. INTERVENTION: Technetium Tc 99m sestamibi scanning. OUTCOME MEASURE: Medical records, operative reports, selective venous sampling results, and sestamibi scans were reviewed to identify scintigraphic findings diagnostic of an undescended parathyroid adenoma. RESULTS: All patients were cured of their persistent or recurrent hyperparathyroidism during reoperation by resection of an undescended inferior parathyroid adenoma. Subsequent review of the preoperative sestamibi scans demonstrated scintigraphic evidence of the undescended adenoma. In each case there was asymmetry in the physiologic activity attributed to the ipsilateral submandibular gland that, in fact, corresponded to an ectopic parathyroid adenoma at the level of the carotid bifurcation. CONCLUSIONS: Careful attention to the contour of radioactivity in the region of the submandibular salivary gland may alert surgeons to the presence of an undescended inferior adenoma. After corroboration, this finding may facilitate a targeted operation.

Adenoma↗

Technetium-99m sestamibi parathyroid localization is accurate enough for scan-directed unilateral neck exploration.

A retrospective study was conducted into technetium-99m sestamibi imaging of primary hyperparathyroidism to determine the accuracy of identification and localization of parathyroid pathology. Of 56 patients studied, 48 had full preoperative scan data, operative data and pathological results analysed. Overall scan accuracy was 96 per cent. For single gland pathology (adenoma) imaging had a sensitivity of 97 per cent, a specificity of 100 per cent and a positive predictive value of 100 per cent. For single gland disease the side was correctly identified in 100 per cent of cases and the site in 94 per cent, but the respective values were only 82 and 79 per cent for multiple gland pathology. Technetium-99m sestamibi imaging is highly sensitive and accurate for primary hyperparathyroidism, with sufficient positive predictive value and accuracy in single gland disease to allow scan-directed unilateral neck exploration.

Follow-Up Studies↗

Detection of occult left ventricular dysfunction in patients without prior clinical history of myocardial infarction by technetium-99m sestamibi myocardial perfusion gated single-photon emission computed tomography.

BACKGROUND: In the absence of a prior history of myocardial infarction (MI), left ventricular (LV) dysfunction is commonly due to hypertension, valvular heart disease, or hibernating myocardium. HYPOTHESIS: Since technetium-99m sestamibi gated single-photon emission computed tomography (SPECT) may be used to determine both stress/rest myocardial perfusion and resting LV function, we attempted to evaluate the ability of gated SPECT imaging to detect occult LV dysfunction. METHODS: We evaluated the ability of this technique to detect occult LV dysfunction among 179 patients without history MI and angiographically documented coronary artery disease (CAD). All patients underwent both gated SPECT and cardiac catheterization within a 6-month time period. Left ventricular volume and ejection fraction (EF) values were determined according to a previously validated technique using Simpson's rule. Normal limit values for LV volumes and EF were derived from a control population of 93 patients with normal coronary angiograms. RESULTS: Based on normal limit-derived criteria, 15% of the CAD study cohort had occult LV dysfunction (> 2 standard deviations below gender-specific normal limit means for LVEF). Mean LV end-diastolic volume index (EDVi) was significantly increased (p < 0.05) and LVEF decreased (p < 0.05) in patients with triple-vessel CAD. End-diastolic volume index was also increased in the cohort of patients with both hypertension and LV hypertrophy (LVH) (p < 0.05). However, multivariate logistic regression analysis revealed that only CAD extent, but not hypertension or LVH, was a significant predictor of occult LV dysfunction (p = 0.009). CONCLUSION: Occult LV dysfunction can be detected in patients with CAD by gating technetium-99m sestamibi SPECT studies, and its presence may signify the presence of extensive CAD.

Adult↗

Technetium-aspirin molecule complexes.

Technetium-aspirin and technetium-aspirin-like molecule complexes were prepared. The structure of N-acetyl-anthranilic acid (NAA) has been decided through CNDO calculations. The ionization potential and electron affinity of the NAA molecule as well as the charge densities were calculated. Comparative studies of the electronic absorption spectra of acetylthio-salicylic acid (ATS) and aspirin (Asp) reveal the structure resemblance in which the acetyl carbonyl group is perpendicular to the plane of the corresponding organic acid. The studies of the electronic absorption spectra of NAA and anthranilic acid reveal the planarity of the NAA molecule. The electronic absorption spectra of Tc(V)-Asp and Tc(V)-ATS complexes have two characteristic absorption bands at 450 and 600 nm, but the Tc(V)-NAA spectrum has one characteristic band at 450 nm. As a comparative study, Mo-ATS complex was prepared and its electronic absorption spectrum is comparable with the Tc-ATS complex spectrum.

Aspirin↗

Pulmonary accumulation of neutral diamine dithiol complexes of technetium-99m.

Twenty-two neutral, lipid-soluble 99mTc complexes have been synthesized from diamine dithiol (DADT) ligands which vary in alkyl substitution pattern on nitrogen and carbon. The logarithm of the partition coefficients (log PC), as well as the capacity factor k', of the purified complexes increased linearly with molecular weight. The biodistribution of these complexes was determined in normal mice, and several of the complexes selectively accumulated in the lungs as compared to the liver or other organs. Pulmonary accumulation varied greatly with subtle changes in structure, and a 30-fold range of lung uptake (1-31% of the injected dose/organ) was observed for isomeric technetium complexes which have identical molecular weights and similar log PC. Further, a parabolic relationship between lung uptake and log PC was observed for a subset of the complexes which are derived from a homologous series of tetramethyl-DADT ligands. Neutral and lipophilic radiopharmaceuticals labeled with technetium can therefore be developed which exhibit structurally specific uptake in the lung.

Animals↗

Sentinel node metastasis in the groin detected by technetium-labeled nannocolloid in a patient with cervical cancer.

OBJECTIVE: The aim of this study was to describe the first sentinel groin node metastasis detected by technetium-labeled nanocolloid in a patient with cervical carcinoma. METHOD: Preoperatively, 60 mBq technetium-labeled nannocolloid was injected at 3 and 9 o'clock in the uterine cervix. Sentinel nodes were detected using a handheld and laparoscopic probe (Navigator) and removed for pathological assessment. RESULTS: A 52-year-old diagnosed with FIGO stage IIA squamous cervical carcinoma was referred to our unit. On physical examination a bulky cervical tumor and a 1.5-cm enlarged left inguinal lymph node were found. No other abnormalities were seen on pelvic MRI scan and CT scan of the abdomen and lower pelvis. Preoperative lymphoscintigraphy showed that a left groin node and three nodes located in the right obturator fossa were the sentinel nodes. They were easily detected using, respectively, a hand-held and a laparoscopic probe and removed. As both the inguinal and the obturator lymph nodes contained metastatic deposits, the patient was treated with the combination of chemotherapy and radiotherapy. CONCLUSION: Inguinal lymph nodes can rarely be the sentinel nodes in patients with cancer of the uterine cervix.

Carcinoma, Squamous Cell↗

Lymphoma imaging with a new technetium-99m labelled antibody, LL2.

The lesion detection capability of a new technetium-99m labelled B-cell lymphoma monoclonal antibody (MoAb) imaging agent, LL2, was evaluated in 8 patients with non-Hodgkin's lymphoma and 1 patient with chronic lymphocytic leukaemia. The MoAb kit consists of a 1-vial, 1-mg Fab' form of LL2 ready for instant labelling with technetium. The patients were injected with approximately 925 MBq (25 mCi) of 99mTc-LL2 Fab' (1 mg), and planar and single photon emission tomography (SPET) studies were performed at 3-4 h post injection and at 24 h. There was no evidence of thyroid or stomach activity up to 24 h. Uniform splenic uptake was seen in all patients. Two non-lymphoma patients were also administered with the same agent and demonstrated a similar splenic distribution; therefore, splenic targeting was not scored as tumour-specific. A total of 29 from 48 tumour sites were detected by scintigraphy, including tumours of various grades and histological types. Excluding 1 patient who had a large tumour burden of over 500 g, 29 of 33 lesions were detected. One patient was free of disease at the time of the study and had a negative scan. Another patient showed excellent targeting of gallium-negative sites in the liver and bone. The bone involvement was not known prior to the antibody study and was subsequently confirmed by a bone scan. Additional sites of MoAb localization could not be followed in this group, since most patients went on to radioimmunotherapy immediately following the 99mTc-LL2 study.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Mediastinal parathyroid localization: possible pitfall in technetium-thallium subtraction scintigraphy.

Two cases of mediastinal localization of parathyroid adenoma are presented, in which technetium-thallium subtraction scintigraphy yielded a positive result. Both patients had already undergone a negative surgical neck exploration. We suggest that, in case of negative subtraction scintigraphy and negative surgical exploration in proven primary hyperparathyroidism, subtraction scintigraphy should be repeated with emphasis on the superior mediastinum, and in all cases, the use of a non-zoom, large field of few procedure is recommended for technetium-thallium subtraction scintigraphy.

Adenoma↗

Technetium-labelled red blood cell scintigraphy: is it useful in acute lower gastrointestinal bleeding?

Radionuclide scintigraphy is commonly utilized as a screening examination before performing more invasive procedures in the work-up of patients with lower gastrointestinal (GI) bleeding. We reviewed our institutional experience with technetium-labelled red blood cell scintigraphy (TRCS) in detecting and localising acute lower GI bleeding. The study group included 72 patients who had 80 red cells scans over a five year period. Thirty-eight scans were positive (47.5%), and 42 were negative (52.5%). Sites of lower GI bleeding were confirmed by endoscopy, arteriography, surgery and/or pathology in 22 of the 38 positive scans. There were four false-negative scans (9.5%). The overall sensitivity and specificity of TRCS in detecting lower GI bleeding was 84.6% (22/26) and 70.4% (38/54), respectively. The accuracy of localization of bleeding sites in the patients with confirmed positive scans was 72.7% (16/22). Thirty mesenteric arteriograms were performed on patients in this series. Eleven arteriograms were performed after negative TRCS; one was positive. Technetium-labelled red blood cell scintigraphy appears to be a useful screening examination for patients with lower GI bleeding who are hemodynamically stable. This may avoid the potential morbidity of arteriography in patients who are not actively bleeding.

Acute Disease↗

Oxygen bubbling can improve the labelling of pentavalent technetium-99m dimercaptosuccinic acid.

It has previously been reported that almost all of the trivalent technetium-99m dimercaptosuccinic acid (99mTc (III) DMSA) present in the labelling product of pentavalent technetium-99m DMSA (99mTc (V) DMSA) can be changed into 99mTc (V) DMSA by bubbling with pure oxygen. We therefore performed studies in animals (mice) and humans to investigate the effect of such oxygen bubbling on the labelling efficiency of and on the renal uptake of 99mTc. The method of labelling of 99mTc (V) DMSA was that of Hirano. It was found that oxygen bubbling oxidized the contaminated 99mTc (III) DMSA into 99mTc (V) DMSA in vitro and decreased the uptake of radioactivity in the kidney in both animals and humans.

Animals↗

Clinical role of technetium-99m sestamibi single-photon emission tomography in evaluating pretreated patients with brain tumours.

One of the main problems regarding the follow-up of patients with brain tumours treated with radiotherapy is the distinction between radiation necrosis and tumour relapse. In many cases computed tomography (CT) scan is unable to distinguish between the two. We assessed the usefulness of brain single-photon emission tomography (SPET) with technetium-99m-sestamibi in cases where CT scan was not conclusive. The absence of tracer uptake in normal brain, the sharp uptake in neoplastic tissue, and the favourable physical properties of technetium make the scintigraphic method particularly accurate. We therefore propose the association of CT scan with 99mTc-sestamibi brain SPET in the follow-up of patients in whom a distinction between radiation necrosis and active disease is needed for an adequate therapeutic decision.

Adolescent↗

Radiolabeling with technetium-99m to study high-capacity and low-capacity biochemical systems.

After a brief review of the history of the development of technetium-99m-labeled radiopharmaceuticals, the use of technetium chelates in high-capacity systems is discussed. The latter are used in the study of five organ systems, the kidneys, liver, bone, brain, and heart. The chemical characterization of 99mTc complexes is also reviewed, followed by discussion of the various approaches to the labeling of proteins with direct labeling, the preformed chelate approach, and the antibody chelator conjugate approach. Thereafter, the labeling of biochemicals with 99mTc for use with easily saturated sites, e.g., receptors and enzymes, is considered. Finally, attention is given to factors that affect the preparation of high specific activity, high affinity 99mTc-labeled biochemicals.

Chelating Agents↗