Copper (II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62Cu or 64Cu is currently under investigation as a radiotracer for imaging the distribution of blood flow with positron emission tomography (PET). The application of a simple trapped tracer model in conjunction with tissue uptake and continuous arterial sampling to estimate blood flow has been compared with the 57Co-microsphere method in the rat. After intraventricular injection the cumulative arterial function for 64Cu increased progressively due to the presence of circulating non lipophilic complexes. The cumulative function for lipophilic 64Cu-PTSM extracted in n-octanol plateaued at levels corresponding to those reached by 57Co-microspheres. No consistent disagreement was found between cardiac output and blood flow estimated by 64Cu-PTSM and 57Co-microspheres in low to moderate flow tissues: muscle (0.08, 0.07 mL/min/g; 64Cu mean, 57Co mean), brain (0.52, 0.43 mL/min/g) and kidney (2.29, 2.45 mL/min/g). However, 64Cu-PTSM underestimated blood flow measured by 57Co-microspheres in myocardium (4.09, 6.55 mL/min/g). A simple tissue trapping model may therefore be suitable for the derivation of blood flow estimates in low to moderate flow tissues using 62,64Cu-PTSM, PET imaging and continuous arterial sampling with n-octanol extraction.
Dynamic cardiomyoplasty improves ventricular function by increasing pump function and by limiting cardiac dilatation. The aim of this study was to assess long-term myocardial performance by radionuclide ventriculography on dilated cardiomyopathy patients subjected to cardiomyoplasty. Thirteen survivors were included. Radionuclide ventriculography was performed one week before surgery and one year later. Five patients were also studied two years following surgery. The left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and ventricular amplitude ratio (VAR) to assess mitral regurgitation were measured. Every case after one year showed a non-significant increase in LVEF. However, the decrease in EDV and in VAR was significant (p < 0.01). No significant difference in these values was found after two years. We conclude that the effects of cardiomyoplasty--reduction of cardiac dilatation, wall stress and mitral regurgitation--are more evident during the first year after surgery. Thereafter, a certain stabilization is observed.
The recent introduction of new tracers and stressors has increased the number of combinations of techniques that can be used for the diagnostic and prognostic stratification of patients with coronary artery disease. However, these new techniques still need to be standardized for clinical use. Thallium-201 scintigraphy is at present the most common method to assess transient ischemia and viability in patients. Dynamic exercise and dipyridamole show similar incidence of major cardiac complications and their use can be considered sufficiently safe. Further experimental and multicenter clinical studies are needed for 99mTc-Sestamibi and 99mTc-Teboroxime and for new stressors such as adenosine and dobutamine.
A case of a patient with small cell lung cancer and right submandibular node enlargement due to granulomatous lymphadenitis is presented. Diagnostic procedures included: biopsy of the cervical node, transmission computed tomography of the chest, bronchoscopic examination and biopsy of the pulmonary lesion. The patient underwent 111In-octreotide scintigraphy (whole body and single photon emission tomography) which revealed both lesions. We conclude that granulomatous lesions are to be considered as a possible cause of false positive results, when octreotide scintigraphy is used to evaluate distant metastases in patients with known cancer.
The effects produced on nuclear perfusion images by exercise-induced changes in the heart and respiration rate and possible transient myocardial stunning are not well understood. In this study we attempted to indirectly evaluate the potential artifacts created by exercise-induced changes in cardiac physiology. Twenty patients with prior myocardial infarction and suspected peri-infarct ischemia were studied by 99mTc-MIBI imaging. Two SPECT perfusion studies were performed after 99mTc-MIBI administration at rest. The first acquisition was carried out 90 minutes after injection of the tracer. Immediately afterwards, the patients underwent a stress test followed by a second acquisition (exercise stress superimposed on rest tracer distribution). A standard stress perfusion scan was also performed 48 hours later. Superimposed exercise stress produced artifactual defects in the resting distribution of the tracer in 15 out of 20 patients (68 of 360 segments). Standard stress images demonstrated concordant defects in 48 of these segments, indicating the concomitant presence of ischemia and stunning. This study indicates that exercise-induced changes in cardiac physiology may result in artifactual perfusion defects in scintigraphic images acquired shortly after the stress.
The distribution of 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI), assessed by single photon emission computed tomography (SPECT) was compared to the distribution of 2-[18F]-2-deoxy-D-glucose ([18F]FDG) assessed with positron emission tomography (PET) under fasting conditions, in 21 patients with coronary artery disease (CAD) and severe left ventricular dysfunction in order to evaluate the potential usefulness of SPECT/99mTc-MIBI for the identification of viable myocardium. Stress and rest SPECT/99mTc-MIBI studies were scored based on the percent of 99mTc-MIBI uptake defined by semi-quantitative circumferential-profile analyses. PET metabolic studies with [18F]FDG under fasting conditions, were adopted as a standard of viability. The results of the comparison of 99mTc-MIBI and [18F]FDG distribution showed that among the segments with stress hypoperfusion, [18F]FDG uptake was present in 95% of the segments that had > 40% of the peak tracer uptake at the rest SPECT/99mTc-MIBI study. [18F]FDG uptake was also present, however, in 25% of the segments that had < 40% uptake at the rest SPECT/99mTc-MIBI scintigraphy. We conclude that in patients with CAD the pattern of 99mTc-MIBI distribution appears to underestimate the extent of viable myocardium but only in those regions that are very severely hypoperfused.
This pharmacokinetic study was performed in order to assess the potential usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin-like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows in fact favourable in vivo localizing properties in the experimental animal model of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area were recorded with a computerized gamma-camera, and specific regions of interest drawn over the liver and spleen helped to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 hours post-injection and daily urine collections over the same interval served to define the kinetics of plama distribution and removal of activity from the body. Different multicompartmental models were tested to fit the experimental data, assuming as the starting hypothesis that there was to be significant nonspecific tracer accumulation in the liver, spleen and bone marrow, as already observed for the majority of radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer in one each); in all these 3 patients immunostaining with the MoAb AR-3 demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and endoluminal/secretory pattern of distribution). Nonspecific radioactivity accumulation in the liver, spleen and bone marrow was extremely low, linked essentially to the blood pool effect of circulating activity in these organs.(ABSTRACT TRUNCATED AT 250 WORDS)
Thirty-five patients with painful bone metastases arising from a variety of tumor types underwent a clinical trial in which 153Sm-EDTMP was injected as a single intravenous dose. The injection ranged in amount from 330 MBq to 1110 MBq of 153Sm-EDTMP. Pain relief usually occurred within one week after administration. The duration of pain relief lasted from 2 to 17 weeks. A detectable degree of pain palliation was experienced by 80% of the treated patients; 54% reported substantial or complete pain relief. Due to the small number of patients, no clear-cut dose-related response was detectable. Moderate myelosuppression was observed in one patient (WHO grade III). The metastatic lesion-to-normal bone ratios remained constant (varying from 1.5 to 4.8) for at least 5 days post-injection. 153Sm cleared very rapidly from the blood. Less than 1% of the injected dose remained in circulation at 4 hours post-injection. No local accumulation of the tracer could be detected outside the skeleton. Urinary excretion was quite complete at 6 hours post-injection. The biodistributions of 153Sm-EDTMP and 99mTc-DPD are very similar in metastatic and normal bone; thus, bone scanning can be used for patient selection and followup. According to our results, it seems that higher doses of 153Sm-EDTMP can be given safely and without any irreversible myelosuppression.
Diethylenetriaminepentaacetic acid (DTPA)-conjugated purified rabbit anti-human serum albumin antibody was subjected to free-flow, semipreparative isoelectrophoresis using an apparatus that fractionates protein molecules based on isoelectric point (pI). The results indicate that (1) the apparatus was capable of developing linear pH gradients and separating proteins, (2) > or = 86% of the protein was recovered following fractionation, and (3) the protein concentration of the individual fractions varied. Focusing the fractions on an isoelectric slab gel revealed that the pIs of the isoforms were modified. The isoforms were radiolabeled with indium-111, their DTPA to antibody molar ratios determined, and their immunoreactivities evaluated by a solid-phase radioimmunoassay. The results demonstrate that (1) the molar ratio of DTPA to antibody varied among the fractions, and (2) the immunoreactivity of the majority of fractions was higher than that of unfractionated DTPA-antibody conjugate. Semipreparative isoelectric focusing may therefore improve the potential of radioimmunoconjugates in the radio-diagnosis and therapy of disease.
In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6-biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues.
Development of a perfusion defect on the 201Tl image from exercise to redistribution is referred to as reverse redistribution, a finding which has been previously associated with several conditions. We describe here two cases in which the reverse-redistribution phenomenon, observed in a routine stress-redistribution thallium-201 scan performed because of chest pain, was considered to be artifactual. Both patients subsequently developed a myocardial infarction in the areas showing the delayed perfusion defect. The potential clinical significance of the reverse-redistribution phenomenon in these two cases is discussed. When observed in patients with typical anginal pain, the reverse redistribution pattern should be considered a potential marker of tissue at risk in a region with previous, otherwise undetected, subendocardial infarction. In such patients the need for coronary angiography should be carefully considered.
Gentamicin is an aminoglycoside antibiotic used to treat a wide variety of infections caused by gram-negative organisms, but it is potentially toxic to the kidneys. Due to its nephrotoxicity, gentamicin may cause abnormal renal uptake to be seen on 99mTc-MDP bone scintigraphy. The presence of the radiopharmaceutical in the kidneys, along with an increase in renal retention, tend to produce scintigraphic results that falsely identify characteristics related to diseases such as renal vascular, or urinary tract obstruction, and even renal cancer. An altered biodistribution may provide misleading information that can either mask or mimic certain disease symptoms. A method to maximize the therapeutic benefit of gentamicin while minimizing the risk of nephrotoxicity and the appearance of a hot kidney on scintigraphy is desirable. Serial pharmacokinetic dosing has been proposed as a method to accomplish this goal. Therapeutic drug monitoring (TDM) of gentamicin therapy, and bone scintigraphy employing 99mTc-MDP as the radiopharmaceutical was carried out in 22 patients. The data presented here demonstrate that with serial pharmacokinetic dosing of gentamicin, the iatrogenic alteration caused by gentamicin therapy can be avoided.
The present study describes extraction fraction and uptake measurements of the [11C]methyl triphenyl phosphonium (11C-MTP), a promising positron emission tomography (PET) agent for cardiac imaging. PET imaging was performed in mongrel dogs. Under physiological flow conditions 11C-MTP uptake reached a maximum within the first 10 minutes after injection and remained constant during the entire observation period of 80 minutes. Over the same time period, the heart/blood ratio was 46-106:1, and the heart/lung ratio 14:1. Following permanent occlusion of the left anterior descending coronary artery, 11C-MTP uptake in the normally perfused myocardium also reached a maximum at 10 minutes after injection, whereas in the infarcted area there was no significant accumulation of 11C-MTP. For a time period of 80 minutes the noninfarcted/infarcted myocardium ratio was 12:1. Extraction was measured in anesthetized dogs with a double isotope method using 99mTc-HSA as the reference tracer. The extraction fraction was 91% at a flow of 69 mL/min/100g. As flow increased to five-fold (342 mL/min/100g) following administration of adenosine, extraction fell to 61%. Following coronary artery occlusion, the 11C-MTP content in the myocardium was highly correlated (r = 0.93, p < 0.01; y = 10.46 + 0.92x) with the microsphere determined regional myocardial blood flow.
In the post-surgical follow-up of a patient with follicular thyroid carcinoma, a palpable mass in the left supraclavicular region was highly indicative of metastatic disease. Technetium-99m methoxy isobutyl isonitrile (99mTc-MIBI) showed an increased but heterogeneous uptake within the lesion. Surprisingly, a different neoplastic disease was histologically demonstrated. Lymph node abnormalities due to non-Hodgkin's lymphoma rather than metastatic thyroid disease were demonstrated. In conclusion, non-Hodgkin's lymphoma may occur in patients with follicular thyroid carcinoma. This new lesion significantly concentrated 99mTc-MIBI. Thus, the results of 99mTc-MIBI imaging have to be carefully evaluated during the follow-up of patients with thyroid cancer.
