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PubMed1993

Technetium-99m mercaptoalbumin as a potential substitute or technetium-99m labelled red blood cells.

Technetium-99m labelled red blood cells (99mTc-RBCs) are far superior to 99mTc-labelled human serum albumin (99mTc-HSA) for radionuclide ventriculography, but their labelling is more complex, time consuming and risk bearing (in vitro labelling) or suffers from interference by some medications (in vivo labelling). We have now modified HSA by the introduction of mercapto groups with the purpose of preparing stable and practical 99mTc-mercaptoalbumin with long retention in the vascular system, that could replace 99mTc-RBCs. HSA was incubated with N-succinimidyl S-acetylthioacetate (SATA) or N-succinimidyl 2,3-di(S-acetylthio) propionate (SATP) to introduce a chain containing one or two protected sulfhydryl groups on some of the lysine amino groups. After purification by size-exclusion chromatography (SEC), the mercapto groups were deprotected by incubation at alkaline pH or by treatment with hydroxylamine. The reaction products were used with or without SEC purification for direct or exchange labelling experiments with 99mTc at neutral pH. SEC-HPLC was used to determine labelling yields and to isolate pure 99mTc-mercaptoalbumin. Stable 99mTc-mercaptoalbumin complexes could be formed in 90%-95% yield after coupling albumin with SATA or SATP in all molar ratios used followed by deacetylation in one of the mentioned conditions. The most favourable results were obtained after reaction of SATA or SATP with HSA in a 25:1 ratio and deprotection with NH2OH. The stability of the resulting 99mTc-mercaptoacetyl-albumin (99mTc-MA-HSA) and 99mTc-dimercaptopropionyl-albumin (99mTc-DMP-HSA) and their retention in vivo in plasma of mice and rabbits are clearly higher than that of conventional 99mTc-HSA preparations. 99mTc-DMP-HSA approaches the behaviour of 125I-HSA quite well in both animal species. A preliminary study with 99mTc-DMP-HSA in a volunteer showed a retention in the vascular compartment almost identical to that of 99mTc-RBCs and clearly higher than that of a common 99mTc-HSA preparation. The results indicate that these 99mTc-mercaptoalbumins and especially 99mTc-DMP-HSA are very promising as a practical alternative to 99mTc-RBCs.

Animals↗
PubMed1990

[Ealuation of thrombolytic treatment of acute myocardial infarct using myocardial scintigraphy with Tc-99-MIBI. Immediate results and follow-up after one year].

The aim of the study was to investigate Single Photon Emission Computed Tomography (SPECT) with technetium-99m esakis-2-methoxy isobutyl isonitrile (Tc-99m-MIBI) as a means of evaluating the results of intravenous thrombolytic treatment in patients with acute myocardial infarction. In addition, the evolution of myocardial perfusion pattern was studied. The study group included 15 patients (12 males and 3 females, mean age 57 +/- 8 years) with acute myocardial infarction admitted to the coronary care unit within 4 hours of the onset of symptoms. All patients were injected with 740 MBq of Tc-99m-MIBI before starting the thrombolytic therapy (rt-PA 100 mg i.v. in 3 hours); SPECT was performed 3 to 6 hours later. The tomographic study was repeated 5 days later. Ten patients were re-examined using Tc-99m-MIBI SPECT one year after the acute event. Taking into account the clinical, electrocardiographic and enzymatic data and the findings of two-dimensional echocardiography performed both on the fifth day and after one month, patients were divided into two groups: group A (8 patients) with probably effective reperfusion, group B (7 patients) probably unaffected by therapy. The infarct related vessel was patent in all group A patients and in 2 of the 7 patients of group B. The percent decrease in the perfusion defect size between the first and second scintigraphic studies showed a significant difference between the two groups: group A 61.2 +/- 6.8, group B 4.7 +/- 2.4% (p less than 0.002). A significant difference was also found when the results of the admission scintigraphy were compared with those of the control 1 year after: group A 80.8 +/- 8.7%, group B 20.8 +/- 13.8% (p less than 0.02). The percent decrease in the perfusion defect size between the 5-day and 1-year images was also significantly different in the two groups: group A 52.9 +/- 20.9%; group B 17.8 +/- 12% (p less than 0.02). The late perfusion improvement involved mainly the sub-epicardial layers. In conclusion, Single Photon Emission Computed Tomography with Tc-99m-MIBI clearly identified patients with effective reperfusion after thrombolytic treatment and distinguished them from subjects unaffected by therapy. Both, successfully and unsuccessfully treated patients showed a late perfusion improvement which was more evident in the successfully treated patients.

Female↗
PubMed2001

Dicarbonyl-nitrosyl-complexes of rhenium (Re) and technetium (Tc), a potentially new class of compounds for the direct radiolabeling of biomolecules.

Re- and Tc-complexes of the oxidation state (+I) offer a useful synthetic pool for the labeling of biomolecules due to their co-ordination properties and stability, which are superior to compounds of the oxidation state (+V). Based on the results for Tc-tricarbonyl complexes it was the topic of this work to develop an access to similar but higher charged compounds, which could be performed by replacing a neutral [CO]-group by a [NO](+)-group. The resulting Re(I)- and Tc(I)-dicarbonyl-nitrosyl complexes, such as [N(CH2CH3)4][ReX3(CO)2(NO)], show a tendency for co-ordination at carboxylic and amine groups of biomolecules (X = Br, Cl). This was shown with picolinic acid (H-pic), a suitable model for amino acids, forming the neutral complex [ReX(pic)(CO)2(NO)]. In a similar fashion conjugation of [188Re(CO)2(NO)](2+)- or [99mTc(CO)2(NO)](2+)-compounds to proteins or antibodies is feasible. This approach opens a way to a potentially new class of radiopharmaceuticals.

Isotope Labeling↗
PubMed1987

Technetium Tc 99m diphosphonate bone scan. False-normal findings in elderly patients with hematogenous vertebral osteomyelitis.

Hematogenous osteomyelitis is usually diagnosed by an abnormal technetium Tc 99m diphosphonate bone scan in symptomatic patients who have positive blood cultures. False-normal 99mTc bone scans have been described recently in neonates with biopsy-proved osteomyelitis. This phenomenon seems to be extremely rare in adults. Two elderly patients with hematogenous vertebral osteomyelitis had normal technetium Tc 99m diphosphonate bone scans when first evaluated. In both cases the bone scans became abnormal four to six weeks after onset of symptoms and two to four weeks after the initial normal results of the study. When suggested by the clinical picture, hematogenous osteomyelitis cannot be ruled out by a normal 99mTc bone scan at any age. Gallium scan, computed tomographic scan, or bone biopsy can be helpful in such cases.

Aged↗
PubMed2000

Cinematic nuclear scintigraphy reliably directs surgical intervention for patients with gastrointestinal bleeding.

HYPOTHESIS: Cinematic technetium Tc 99m red blood cell ((99m)Tc-RBC) scans, in which real-time scanning is performed and analyzed, can accurately localize gastrointestinal bleeding and thus direct selective surgical intervention. DESIGN: Retrospective medical record review with historical controls. SETTING: Large, university-affiliated public hospital in urban setting. PATIENTS: Twenty-six patients presenting with upper and lower gastrointestinal hemorrhage who underwent cinematic (99m)Tc-RBC scan examinations between 1990 and 1997 and required surgical intervention to control the bleeding. INTERVENTIONS: All patients with gastrointestinal bleeding underwent open surgical procedures to provide cessation of bleeding and resection of appropriate abnormalities. MAIN OUTCOME MEASURES: Patient outcome was based on correlation between preoperative RBC scans and intraoperative findings, surgical pathology, and postoperative clinical course. RESULTS: Twenty-five (96%) of 26 scans were interpreted as positive for gastrointestinal bleeding. In 22 of these 25 scans, the site of bleeding was correctly identified for a sensitivity of 88%. One or more additional diagnostic tests were performed on 19 (73%) of 26 patients, and included angiography and flexible endoscopy. The most common operation performed to control bleeding was a hemicolectomy (14/26). Diverticulosis was the most prevalent diagnosis (46%). Two patients (8%) experienced rebleeding after operation. The overall mortality rate was 19% (5/26). CONCLUSIONS: Cinematic (99m)Tc-RBC scintigraphy is a sensitive, noninvasive alternative to mesenteric angiography for accurately localizing the site of gastrointestinal hemorrhages. As such, this technique can be reliably used to direct selective surgical intervention.

Adult↗
PubMed2000

Splenic function in sickle cell anemia patients in Qatif, Saudi Arabia.

A prospective study was conducted to study the splenic function among sickle cell anemia (SCA) patients in Qatif (Eastern Province of Saudi Arabia). Seventy-seven patients (30 children and 47 adults aged 2-57 years) were included. (99m)Tc stannous colloid liver-spleen scan was done for each patient during steady state. The splenic function was graded from 0 to 4 in relation to liver uptake. Seventy percent of our patients showed evidence of splenic hypofunction, and most of them (83%) had severe hyposplenism. Up to the age of 4 years, only 17% of the children showed evidence of functional hyposplenism, but by the age of 10 years >50% were hyposplenic. Most of the hyposplenic children had functional hyposplenism, whereas only one-third of hyposplenic adults had autosplenectomy. There was no effect of level of HbF on the frequency of hyposplenism, but on the other hand low MCV seems to be protective against hyposplenism. A significant number of adult SCA patients have clinically enlarged spleens, and almost a third have normally functioning spleens. Because of the low prevalence of hyposplenism in children younger than 4 years of age, routine penicillin prophylaxis is probably not indicated in this population, an issue which needs further evaluation.

Adolescent↗
PubMed2001

OPEC/OJEC for stage 4 neuroblastoma in children over 1 year of age.

BACKGROUND: This paper reports the toxicity of OPEC/OJEC chemotherapy in stage 4 neuroblastoma patients over 1 year of age. PROCEDURE: Ninety-five patients with stage 4 neuroblastoma received alternating courses of OPEC/OJEC--vincristine 1.5 mg/m2 (O), cisplatin 80 mg/m2 (P), etoposide 200 mg/m2 (E), cyclophosphamide 600 mg/m2 (C), and carboplatin 500 mg/m2 (J), every 21 days if there was haematological recovery. RESULTS: Seventy out of ninety-five (74%) patients completed seven or more courses and were evaluable for toxicity. Of these 70 patients, 33% had more than three episodes of fever and sepsis, 35% required more than five blood or platelet transfusions, 36% had grade 2 or more gastrointestinal toxicity and 9% had neurotoxicity. There was a median reduction in GFR of 32 ml/min/1.73 m2 (-46 to 134) and there was one toxic death. CONCLUSIONS: OPEC/OJEC is a well-tolerated therapy for stage 4 neuroblastoma over 1 year of age.

3-Iodobenzylguanidine↗
PubMed1981

The diagnosis and detection of urogenital cancers.

Previously, histologic precision in the diagnosis of urologic cancers had, for some time, remained stable. More recently, variations in classifications of testis tumors, prostate cancer, and to some degree, bladder tumors, have been introduced. Most systems have in concurrence a desire or an attempt to infer better prognostic assessment in the overall results to treatment. With the advent of additional biological markers or direct enzymatic measurements, e.g., in prostate cancer, further improvements in identifying at risk populations, responses to treatment, and possible indications for variations in treatment, have ensued. These developments alone unquestionably mark the greatest area of change in the recent decade. The extent of disease assessment prior to definitive therapy, whether by arteriography, ultrasound, CAT scanning, or an occasional lymphangiography, has also influenced or modified treatment decisions. For continuing care and follow-up, several of these noninvasive techniques are now becoming included in the more standard approaches. Noninvasive techniques have been introduced for the therapy of renal tumors such as inducing infarction of the primary tumor. Endoscopic ultrasonic techniques have been particularly useful in assessing the size of pelvic tumors and response to treatment, even in detection of unexpected multiple primaries or metastatic extensions. Overall, the precision in urologic cancer, both for diagnostic and detection purposes, has been increased with these introductions.

Angiography↗
PubMed1985

Radionuclide lymphoscintigraphy with technetium 99m antimony sulfide colloid to identify lymphatic drainage of cutaneous melanoma at ambiguous sites in the head and neck and trunk.

Frequently the primary lesion of high-risk cutaneous melanoma (level III, greater than or equal to 1.5mm; greater than or equal to 1.0 mm with ulceration) is in an ambiguous lymphatic drainage site on the trunk, pelvic and shoulder girdles, and head and neck area. Lymphoscintigrams were performed by a circumferential intradermal injection of the biopsy site using technetium 99m (99mTc) antimony sulfide colloid in a total dose of 0.2 to 0.6 mCi in a volume of 0.1 to 0.5 ml. Imaging was done with a large-field gamma camera with high-resolution parallel hole collimator. Technetium 99m antimony sulfide colloid is an ideal agent for lymphoscintigrams because of small particle size (3-30 micron), which permits early migration into the interstitial space and lymphatics and rapid pickup by lymph nodes. Although it is a gamma emmitter with high activity, it has a short half-life and does not induce tissue necrosis. It does not localize the site of lymph node metastases, but indicates only the drainage pattern. Images were obtained at 1, 5, 10, 15, 30, and 60 minutes, respectively, and then three times every hour. Surgery was usually performed 24 hours later. The majority of patients had lesions with ambiguous drainage sites: head and neck (4 of 5 patients) and trunk (9 of 13 patients). The drainage by scan was to unpredictive sites in 72%, and resulted in a change of treatment planning by location and extent of ablation with node dissection in 9 of 18 patients. Ambiguous dissection sites included: (1) question of preauricular dissection with parotidectomy versus posterior auricular and cervical dissection for selected scalp lesions; (2) low-neck with or without axillary dissection for upper chest and shoulder lesions; and (3) axillary versus groin dissections for midflank lesions at zone of ambiguity between axilla and groin. It was concluded that preoperative 99mTc antimony sulfide lymphoscintigraphy is a highly useful planning technique in determining the appropriate lymphatic drainage basin for dissection in selected melanoma patients.

Adult↗
PubMed1986

Radionuclide lymphoscintigraphy performed on the mastectomized chest wall.

Lymphatic flow in the anterior chest wall of 64 patients who underwent surgery for breast carcinoma was studies on images of lymphoscintigraphy using 99mTc-rhenium colloid. Scintigraphic images taken 4 hours after the intradermal injection of radionuclides along both sides of the surgical wound frequently made it possible to visualize the contralateral axillary lymph nodes. In particular, among 20 patients with local chest wall recurrence after the mastectomy, the contralateral axillary nodes were demonstrated in 13. Stimulated lymphatic flow seems to be manifested around the site of local recurrence over the chest wall. On the precise analysis of lymphographic images, faint lymphatic drainages were occasionally identified up to the contralateral axillary lymph nodes at various levels of the anterior chest wall. It is essential that the radiation field be made large towards the area including the downstream of the lymphatic flow. Additionally, accumulation of radionuclides in the lymph nodes appeared to be slowly impaired by the postoperative irradiation after the completion of radiotherapy.

Adult↗
PubMed2000

In vivo measurements of relaxivities in the rat kidney cortex.

The aim of this study was to implement a novel noninvasive method to derive the in vivo T1 relaxivity (R1) and T2 relaxivity (R2) in the rat kidney cortex. A two-compartment gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) distribution model was established to estimate the bolus and infusion dosages of Gd-DTPA necessary for obtaining the required steady-state concentration levels. After a single bolus injection of (99m)Tc-DTPA, several blood samples were collected. Based on considerations from the applied two-compartment model, a steady-state concentration was predicted approximately 5-10 minutes after the bolus injection. The plasma concentration levels of Gd-DTPA were measured by simultaneous injection of (99m)Tc-DTPA. Three regions in the cortex (upper, central, and lower) of both rat kidneys were used. A statistical evaluation resulted in the following in vivo relaxivities found at 7 T: R1 = 1.04 +/- 0.08 mM(-1)s(-1) and R2 = 10.78 +/- 0.83 mM(-1)s(-1). Using a 95% confidence interval, no intracortical differences were detected. The relaxivities R1 and R2 calculated in the intact rat kidney cortex were distinctly different from relaxivities found in human plasma: (22 degrees C) 4.42 +/- 0.07 mM(-1)s(-1) (r2> 0.98) and R2 = 5.75 +/- 0.17 mM(-1)s(-1) (r2> 0.98), respectively. The measurements showed a marked difference between in vitro and in vivo relaxivities. Comparison of the distribution rates in pig, human, and rats shows a distinct proportionality between size and renal function.

Animals↗
PubMed2002

Temporal sequence of splenic dysfunction in sickle cell disease.

Sickle cell patients develop splenic dysfunction early in the course of their disease as shown by failure to visualize the organ on technetium-99m colloid scintigraphy. However, preliminary studies from our center have shown that, when the spleen is not demonstrable on colloid uptake, it may be visualized on technetium-99m heat-denatured RBC scintigraphy. With time, however, the spleen can no longer be visualized with both tests in many patients. We have studied 46 patients aged 2 to 16 years, which included 36 SS, 7 Sbeta(0) thal, and 3 SD. Eighteen (39.1%) had normal splenic colloid uptake (Group 1), 15 (32.6%) had partial uptake (Group 2), and 13 (28.3%) had absent uptake (Group 3). When the patients in Group 1 were compared to those in the two other groups, there was no significant difference in the mean age and Hb F values. However, the mean Hb of 10.2 g/dl in Group 1 was significantly higher than the value of 9.0 g/dl in the other two groups. In addition, 60% of the SS patients with normal uptake and 40% of those with partial or absent uptake had co-existing alpha-thal trait; the difference in this proportion is significant (chi(2) = 85, P < 0.0001). Heat-denatured RBC scintigraphy was carried out on five patients in Group 2, and the spleen was visible in all, while of 12 children in Group 3, the spleen was visible only in 4 patients. This study demonstrates that the phagocytic function of the spleen, which is tested by colloid uptake, is the first to be lost while the filtration function, tested by denatured RBC uptake, persists for much longer. This finding may have significant implications for the clinical symptomatology and therapeutic strategies of sickle cell disease.

Adolescent↗
PubMed1991

Insufficiency fractures of the distal tibia misdiagnosed as cellulitis in three patients with rheumatoid arthritis.

We describe 3 patients with rheumatoid arthritis who presented with diffuse pain, swelling, and erythema of the distal aspect of the lower extremity, suggestive of either cellulitis or thrombophlebitis, but were found to have insufficiency fractures of the distal tibia. The value of technetium-99m diphosphonate bone scintigraphy in the early recognition of these fractures and a possible explanation for the associated inflammatory symptoms are discussed.

Aged↗
PubMedDate not supplied

Normal pharmacokinetics of 99mTc-diphosphonate after intravenous administration.

In the past several years bone imaging has become a routine diagnostic tool for the nuclear medicine clinician. However, increased information may be derived by determining the ratio-pharmacokinetic parameters associated with blood, urine, and bone. In an adult male population of normals (N = 5--6) blood clearance, urinary excretion, and skeletal uptake of 99mTc-Diphosphonate were determined as a function of time after intravenous (i.v.) administration. The quantitative imaging studies (lower lumbar region) were performed up to 1 h post administration with a scintillation camera interfaced to a computer. Blood levels exhibited a triexponential clearance pattern and urinary excretion of the radiopharmaceutical was essentially complete by 4 h. The computer-generated images showed an initial early uptake in bone, kidneys, and soft tissue. Thereafter, a parallel fall-off in activity was observed in kidneys and soft tissue, with a concomitant increase in bone.

Adult↗
PubMed1981

High colloidal uptake in axillary nodes with metastatic disease.

Axillary lymphoscintigraphy using 99Tcm antimony sulphide colloid has been carried out in 29 patients with suspected breast cancer and was correlated with histology. Of the 23 with proved tumour, axillary node metastases were found in 19 and, although 10 did have diminished uptake on the side of the lesion, 5 had an equal uptake in both sides and 4 had an increased uptake on the side of the lesion. Further, some of the nodes in which the high uptake had occurred were those heavily infiltrated by tumour. It is concluded that: a, lymphoscintigraphy with antimony sulphide colloid is not a reliable technique for the detection of metastatic disease in the regional nodes; b, any lymphoscintigraphy with this or any other agent requires more meticulous histological correlation than hitherto before it can be assumed to have any proved clinical value.

Antimony↗