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Biomedical subjects

C J Palestro

Publications and source records attributed to C J Palestro.

At least 19 recordsLinked to original sources

Recombinant human thyroid-stimulating hormone-aided scintigraphy: comparison of imaging at multiple times after I-131 administration.

PURPOSE: Recombinant human thyroid-stimulating hormone (rhTSH) may be used in lieu of thyroid hormone withdrawal for the evaluation of thyroid cancer. Scintigraphy using the existing rhTSH protocol is performed 48 hours after I-131 administration. The authors investigated the feasibility of whole-body imaging at 72 hours and evaluated thyroid tissue uptake at 48 to 144 hours. METHODS: Thirty-two patients who previously had thyroidectomy for thyroid cancer were examined. Whole-body imaging was performed routinely at 48 and 72 hours after I-131 administration. Thyroid tissue was visualized in 12 patients, and large foci were imaged for as long as 144 hours. Activity ratios for thyroid tissue to background were determined for 10 patients. RESULTS: Whole-body images at 48 and 72 hours were comparable, generally with lower background activity at 72 hours, and thyroid tissue was well visualized at all times after 48 hours. Thyroid tissue-to-background activity ratios at 72 to 144 hours were equal to or greater than those at 48 hours in 9 of 10 patients. CONCLUSIONS: Recombinant human TSH-aided whole-body scintigraphy is possible 72 hours after I-131 administration, adding flexibility and convenience to the existing protocol and permitting confirmation of findings at 48 hours. Tracer uptake in thyroid tissue persists at later times. Therefore, rapid clearance of background activity appears to be the primary cause of the previously reported decrease in radioiodine retention in euthyroid persons receiving rhTSH.

Humans↗

Localizing infection with a technetium-99m-labeled peptide: initial results.

In vitro-labeled leukocyte imaging is useful for the detection of infection, but an in vivo labeling method is preferable. This study sought to evaluate the safety and efficacy of a leukocyte-avid peptide for the detection of infection, to determine the effects of peptide dose on performance and to compare the peptide with in vitro-labeled leukocytes. A 23-amino acid peptide, P483, containing the platelet factor-4 heparin-binding sequence, was labeled with 99mTc and complexed with heparin (P483H). Thirty patients were injected with 29 microg (n = 11), 145 microg (n = 10) or 290 microg (n = 9) of labeled peptide, and imaged 15 min and 90-120 min later. Early and late images were interpreted individually and jointly. Twenty patients underwent (111)In-labeled leukocyte scintigraphy. Fourteen patients had infection: osteomyelitis (n = 7), vascular graft (n = 2), abscess (n = 2), joint replacement (n = 1), surgical wound (n = 1) and pneumonia (n = 1). There were 10 adverse events in six patients; all were mild and resolved spontaneously, and without any intervention. The sensitivity, specificity and accuracy were the same for both early and late imaging: 0.86, 0.81 and 0.83, respectively. Interpreting early and late images together did not improve the results. No relationship between peptide dose and study accuracy was found. In patients undergoing both examinations, the accuracies of the peptide and in vitro-labeled leukocyte imaging were identical: 0.80. In summary, 99mTc-P483H safely, rapidly and accurately detected focal infection, was comparable with in vitro-labeled leukocyte imaging and therefore merits further investigation.

Adult↗

Integration and proliferation of transplanted cells in hepatic parenchyma following D-galactosamine-induced acute injury in F344 rats.

To determine whether liver repopulation with cell transplantation could be of therapeutic value in acute hepatic failure, it is necessary to establish the fate of transplanted hepatocytes. This study used dipeptidyl peptidase IV-deficient F344 rats as recipients to analyse the engraftment and proliferation of transplanted hepatocytes. Syngeneic hepatocytes were transplanted intrasplenically 24-30 h after induction of liver injury by D-galactosamine (GalN). Portosystemic shunting was analysed with 99m-Tc-labelled albumin microspheres. GalN-treated rats showed characteristic hepatic necrosis, inflammation, gamma-glutamyl transpeptidase activation, and regenerative activity, without increased portosystemic shunting (>99% 99m-Tc activity was in the liver in normal and GalN-treated rats). Transplanted cells entered hepatic sinusoids promptly and were observed in liver plates at 48 h. The number of transplanted cells increased in GalN-treated rats by approximately seven-fold (range two- to 12-fold), along with evidence for DNA synthesis between 3 and 14 days after cell transplantation and greater prevalence of larger transplanted cell clusters. These findings indicate that the liver can be safely repopulated in animals with acute liver failure, although the time required for regenesis of plasma membrane structures and proliferation in transplanted hepatocytes will need to be considered in developing therapeutic strategies.

Animals↗

Transplanted hepatocytes engraft, survive, and proliferate in the liver of rats with carbon tetrachloride-induced cirrhosis.

Repopulation of the cirrhotic liver with disease-resistant hepatocytes could offer novel therapies, as well as systems for biological studies. Establishing whether transplanted hepatocytes can engraft, survive, and proliferate in the cirrhotic liver is a critical demonstration. Dipeptidyl peptidase IV-deficient F344 rats were used to localize transplanted hepatocytes isolated from the liver of syngeneic normal F344 rats. Cirrhosis was induced by administration of carbon tetrachloride with phenobarbitone and these drugs were withdrawn prior to cell transplantation. Cirrhotic rats showed characteristic hepatic histology, as well as significant portosystemic shunting. When hepatocytes were transplanted via the spleen, cells were distributed immediately in periportal areas, fibrous septa, and regenerative nodules of the cirrhotic liver. Although some transplanted cells translocated into pulmonary capillaries, this was not deleterious. At 1 week, transplanted cells were fully integrated in the liver parenchyma, along with expression of glucose-6-phosphatase and glycogen as reporters of hepatic function. Transplanted cells proliferated in the liver of cirrhotic animals and survived indefinitely. At 1 year, transplanted hepatocytes formed large clusters containing several-fold more cells than normal control animals, which was in agreement with increased cell turnover in the cirrhotic rat liver. The findings indicate that the cirrhotic liver can be repopulated with functionally intact hepatocytes that are capable of proliferating. Liver repopulation using disease-resistant hepatocytes will be applicable in chronic conditions, such as viral hepatitis or Wilson's disease.

Animals↗

Diagnosing spinal osteomyelitis: a comparison of bone and Ga-67 scintigraphy and magnetic resonance imaging.

PURPOSE: The objective of this investigation was to compare the accuracies of bone and Ga-67 scintigraphy and magnetic resonance imaging (MRI) for diagnosing spinal osteomyelitis and to determine the optimal radionuclide approach to this disorder. METHODS: Twenty-two patients, with 24 sites of possible spinal osteomyelitis, who underwent three-phase bone scintigraphy with SPECT, Ga-67 scintigraphy with SPECT, and MRI with and without contrast were included in this retrospective review. Bone scans were interpreted as three-phase studies, delayed planar images alone, delayed planar plus SPECT, and SPECT alone (to identify uptake patterns). Sequential bone/ Ga-67 images were interpreted as planar and as SPECT studies. Planar and SPECT Ga-67 images were also interpreted alone. Precontrast MRI studies were used to identify osteomyelitis, whereas postcontrast images were used to identify soft tissue infection. RESULTS: Eleven sites of spinal osteomyelitis were identified. Tracer uptake in two contiguous vertebrae, as noted on SPECT, was the most accurate bone scan criterion for detecting spinal osteomyelitis (71 %). SPECT bone/Ga-67 was significantly more accurate (92%) than both planar bone/Ga-67 (75%) and bone SPECT (P = 0.15 and P = 0.2, respectively). SPECT Ga-67 was as accurate as SPECT bone/Ga-67 and as sensitive as MRI (91 %); the radionuclide study was slightly but not significantly more specific (92% vs. 77%) than MRI. Of 11 sites of extraosseous infection, 10 were identified on MRI, 9 on SPECT Ga-67, 7 on planar Ga-67, and none on bone scintigraphy. CONCLUSIONS: Spinal osteomyelitis and accompanying soft tissue infection can be diagnosed accurately with a single radionuclide procedure: SPECT Ga-67. This procedure can be used as a reliable alternative when MRI cannot be performed and as an adjunct in patients in whom the diagnosis is uncertain.

Adult↗

The diabetic foot.

Foot complications in diabetics often lead to amputation. Ulceration is the most common complication in the diabetic forefoot and underlies more than 90% of cases of pedal osteomyelitis. The diagnosis of osteomyelitis is, nevertheless, difficult, and imaging is an important part of the work-up. Plain radiographs, although useful for anatomical information, are neither sensitive nor specific. Three-phase bone scintigraphy is sensitive but not specific. Labelled leucocyte scintigraphy and MRI are both useful and are complementary to one another. Labelled leucocyte scintigraphy is valuable for diagnosis as well as follow-up of pedal osteomyelitis. MRI offers exquisite anatomical detail, which is invaluable for guiding surgical management. The principal complication in the mid and hind foot is the neuropathic or Charcot joint. Although infection of the neuropathic joint is infrequent, its diagnosis is difficult. The extensive bony changes that accompany this disorder severely diminish the value of radiography and bone scintigraphy. It is not always possible to distinguish the marrow oedema of neuropathy from that of osteomyelitis and the role of MRI in the evaluation of this entity is still uncertain. Uptake of labelled leucocytes in the absence of infection may occur and is owing, at least in part, to haematopoietically active marrow. Combined leucocyte/marrow scintigraphy holds considerable promise for identifying the infected Charcot joint.

Arthropathy, Neurogenic↗

Radionuclide analysis of drug-induced blood-pool changes in liver and other organs.

UNLABELLED: Although it is possible to repopulate the animal liver with transplanted hepatocytes, the success of such transplants depends, in part, on the number of transplanted cells that enter the hepatic sinusoids. Pharmacologic alteration of hepatic vascular tone, and hence blood volume, can increase the number of cells that are successfully transplanted. Although analysis of changes in vascular beds is helpful for developing strategies for cell transplantation, convenient methods to analyze such changes are lacking. The objective of this study was to determine whether 99mTc-labeled red blood cells could be used to reveal pharmacologically induced blood pool changes in various organs. METHODS: F344 rats were injected with syngeneic labeled red blood cells and subjected to blood pool analysis with gamma camera imaging. Animals were treated with phenylephrine, phentolamine, labetalol, and nitroglycerine. To correlate hepatic blood pool changes with structural alterations at the vascular level, microspheres were injected into the portal circulation of these animals. RESULTS: Phenylephrine significantly increased cardiac and pulmonary blood pools, findings in agreement with its alpha-adrenergic effects. Phentolamine increased the hepatic, splenic, and pulmonary blood pools, whereas labetalol increased only the pulmonary blood pool. Nitroglycerine increased both hepatic and splenic blood pools. Prior administration of phentolamine, labetalol, and nitroglycerine prevented the phenylephrine-induced changes. When microspheres were injected into the portal circulation after nitroglycerine administration, they penetrated more distal locations in the liver lobule. CONCLUSION: These data indicate that it is possible, using radionuclide methods, to noninvasively show pharmacologically induced hemodynamic changes. This finding is potentially useful for studying hepatic physiology and may also have applications for cell therapy.

Animals↗

Synthesis of aminobenzyltriethylenetetraaminohexaacetic acid: conjugation of the chelator to protein by an alkylamine linkage.

The conjugation of a chelating agent to an antibody as an anchoring site for a radionuclide is the first step in the successful preparation of a radiolabeled antibody for a diagnostic and therapeutic application. The high affinity of the protein bound chelator towards radionuclide ensures a higher selectivity in the delivery of the radionuclide to the targeted tissue. 4-Aminobenzylderivativetriethlenetetraaminohexaacetic acid (TTHA), a hexadentate chelating agent has been now prepared for conjugation with proteins in view of the higher affinity of TTHA metal ions as compared to DTPA. The latent crosslinking potential of alpha-hydroxy aldehydes has been used to conjugate the new chelating agent to proteins through an alkylamine linkage. On incubation of amino benzyl TTHA with glycoladehyde at neutral pH and room temperature, the reagent is converted to oxo ethyl amino benzyl TTHA. On addition of albumin to this reaction mixture, the oxo ethylamino benzyl TTHA generates reversible schiff base adducts with the amino groups of albumin. The reduction of the Schiff base adducts of the chelator with the protein by sodium cyanoborohydride stabilizes the schiff base adducts as stable alkylamine linkages. 4-Thiocyanatobenzyl TTHA has also been prepared and conjugated to albumin through a thiocarbamoyl linkage. Both preparations of TTHA conjugated albumin complexed with 99mTc and 111In, with high affinity and no decomposition of the complex was noticed for at least up to 6 hrs after the preparation. The radiolabels complexed with these TTHA -albumin conjugates could not be 'chased' out by free DTPA. A comparison of the biodistribution of 111In, bound to the TTHA conjugated through an alkylamine and a thiocarbamoyl linkage showed that 111In complexed with alkylamine linked TTHA was retained in blood to a level nearly 17% higher compared to that seen with thicarbamoyl linked TTHA, one hr after the injection into mice. Thus, the alkylamine linkage appears to be more stable under the in vivo conditions. The glycolaldehyde mediated alkylation procedure offers a mild, simple and rapid method for preparation of drug-protein (antibody) conjugates.

Acetates↗

Radionuclide imaging of nonosseous infection.

Nuclear medicine is an important tool in the diagnostic evaluation of patients with a variety of nonosseous infections. In the immunocompetent population labeled leukocyte imaging is the radionuclide procedure of choice, with Gallium imaging reserved for those situations in which the leukocyte study is nondiagnostic or cannot be performed. Fever of unknown origin is caused by infection in less than one-third of cases, and therefore the number of positive leukocyte studies will be relatively low. The negative leukocyte study is also useful, however, as it has been demonstrated that a negative study excludes, with a high degree of certainty, focal infection as the cause of an FUO. In the cardiovascular system, labeled leukocyte scintigraphy is very useful for diagnosing mycotic aneurysms and infected prosthetic vascular grafts, with a sensitivity of about 90%. The specificity of the study is somewhat more variable--false positive results have been described in perigraft hematomas, graft thrombosis, bleeding, and pseudoaneurysms. In the central nervous system, labeled leukocyte imaging can provide important information about the etiology of contrast enhancing brain lesions identified on computed tomography, i.e., distinguishing between neoplasm and infection. In the immunocompromised population, typified by the AIDS patient, Gallium scintigraphy is the radionuclide procedure of choice for diagnosing opportunistic diseases. In the thorax, a normal Gallium scan, in the setting of a negative chest X-ray, virtually excludes pulmonary disease. A negative Gallium scan in a patient with an abnormal chest X-ray and Kaposi's sarcoma study suggests that the patient's respiratory problems are related to Kaposi's sarcoma. Focal pulmonary parenchymal uptake is most often associated with bacterial pneumonia, although Pneumocystis carinii pneumonia can occasionally present in this fashion. Diffuse pulmonary parenchymal uptake of Gallium can be due to numerous causes, but in general, the more intense the uptake, the greater the likelihood that the patient has P. carinii pneumonia. Lymph node uptake is most often due to lymphoma or mycobacterial disease. In the abdomen, Gallium is also useful for detecting nodal disease. but is not reliable for detecting large bowel disease. Labeled leukocyte imaging should be performed when colitis is a concern. Both 18FDG PET and 201Tl SPECT imaging of the brain are useful for distinguishing between central nervous system lymphoma and toxoplasmosis in the HIV (+) patient. On both studies, lymphoma manifests as a focus of increased tracer uptake, whereas toxoplasmosis shows little or no uptake of either tracer.

AIDS-Related Opportunistic Infections↗

Improved tumor targeting of rhenium-186-labeled anti-human high-m.w. melanoma-associated antigen monoclonal antibody 763.74 following purification with anti-idiotypic monoclonal antibody MK2-23.

Because of its high-energy beta emissions and imageable gamma emissions, 186Re represents an attractive isotope to radiolabel monoclonal antibodies (MAbs) recognizing human tumor-associated antigens (TAAs) for radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) of patients with malignant diseases. Application of 186Re, however, is hindered by the frequent denaturation of MAbs following exposure to the strong reducing conditions employed in the labeling procedures. To overcome this problem, we have utilized a direct labeling procedure and combined it with affinity chromatography over columns of immobilized anti-idiotypic (anti-id) MAbs which recognize idiotopes in the antigen-combining site of the radiolabeled MAb. The validity of the procedure was demonstrated with the anti-high-m.w. melanoma-associated antigen (HMW-MAA) MAb 763.74 and its corresponding anti-id MAb MK2-23. Utilizing this approach, MAb 763.74 was labeled to specific activities of 2.8 +/- 0.6 mCi/mg with 186Re. Furthermore, its immunoreactivity, which was reduced to about 30% following labeling with 186Re, was improved to about 50% by affinity chromatography over columns of anti-id MAb MK2-23. The improvement in immunoreactivity of 186Re MAb 763.74 resulted in a significant (p < 0.05) increase in targeting to human melanoma tumors grown in nude mice and an increase in sensitivity of RIS. Our results suggest that direct labeling of anti-TAA MAb with 186Re coupled with purification over affinity columns of anti-id MAb may facilitate the application of 186Re to RIS and RIT.

Animals↗

111Indium pentetreotide scan detection of familial paragangliomas.

Approximately 10% of head and neck paragangliomas are familial. Magnetic resonance imaging (MRI) is reported to be the best method for screening these families. 111Indium pentetreotide (Octreoscan) scintigraphy has been shown to be a sensitive indicator of neural crest tumors such as paragangliomas. Early diagnosis and treatment of familial paragangliomas (FP) would decrease the morbidity of tumor excision. Patients from two kindred with FP were scanned 24 hours after intravenous injection with approximately 6 millicuries of 111Indium pentetreotide. The entire body was imaged. Areas of increased uptake were further imaged with MRI. Altogether, five patients had positive 111Indium pentetreotide scans. Two unsuspected glomus tympanicums and bilateral carotid body tumors were identified. Three people tested had no abnormal uptake. There were no untoward reactions to the nuclide. 111Indium pentetreotide scanning is a safe, noninvasive method for early diagnosis of FP and is useful in detecting multicentric lesions. Patients suspect for FP are undergoing 111Indium pentetreotide imaging and followed up with MRI of the involved site if positive.

Adult↗

Marrow versus infection in the Charcot joint: indium-111 leukocyte and technetium-99m sulfur colloid scintigraphy.

UNLABELLED: This study evaluated the role of combined leukocyte/marrow scintigraphy in the assessment of the neuropathic or Charcot joint. METHODS: Seventeen patients with (111)In-labeled leukocyte accumulation in 20 radiographically confirmed Charcot joints underwent 99mTc-sulfur colloid marrow scintigraphy. Studies demonstrating labeled leukocyte accumulation without corresponding activity on marrow images were classified as positive for osteomyelitis. Six of the patients also underwent three-phase bone scintigraphy. Bone scans were interpreted as positive for osteomyelitis when focal hyperperfusion, focal hyperemia and focal bony uptake on delayed images were present. Bone images were also interpreted together with labeled leukocyte images using two different criteria for a positive study. One criterion was the presence of labeled leukocyte activity in a region demonstrating abnormal activity on the bone scan, which was more intense than adjacent marrow activity or marrow activity in the corresponding region of the contralateral foot. The second criterion was either a spatially incongruent distribution of the two tracers or hyperintense activity on the leukocyte study, as compared to the bone scan. RESULTS: Leukocyte/marrow studies were positive for osteomyelitis in 4 of the 20 neuropathic joints. Osteomyelitis was present in three of the four joints, whereas in the fourth, infection was confined to overlying soft tissues. None of the 16 neuropathic joints with negative leukocyte/marrow scans were infected. In one patient who underwent below-the-knee amputation, histological analysis confirmed the presence of hematopoietically active marrow corresponding to areas of congruent activity on the leukocyte and marrow images. Three-phase bone scintigraphy was positive in all six neuropathic joints studied; osteomyelitis was present in two of them. Using the first criterion, leukocyte/bone imaging was also positive in all six. Using the second criterion, leukocyte/bone imaging was positive in the two infected neuropathic joints, as well as in three uninfected ones. Leukocyte/marrow scintigraphy was positive in both infected joints and negative in the four without infection. CONCLUSION: Labeled leukocyte accumulation in the uninfected Charcot joint does occur and is related, at least in part, to hematopoietically active marrow. Leukocyte/marrow scintigraphy is a reliable way to differentiate between marrow and infection as the cause of labeled leukocyte accumulation in the neuropathic joint and, in this series, was superior to both three-phase bone scintigraphy and combined leukocyte/bone scintigraphy.

Adult↗

Radionuclide imaging in orthopedic infections.

In otherwise normal bone, Three Phase Bone Scintigraphy is sensitive and specific for osteomyelitis. In patients with underlying osseous abnormalities the specificity of the study is decreased. The four phase bone scan, bone/gallium scintigraphy, leukocyte imaging, leukocyte/bone and leukocyte/marrow studies have all been reported to increase specificity. The techniques, strategies, and limitations are discussed. No single study is equally useful in all situations. Labeled leukocyte imaging is of little value in vertebral osteomyelitis because this entity often presents as a nonspecific photopenic defect. The preferred technique for the spine is bone/gallium imaging. Intense uptake, on bone scintigraphy, in two adjacent vertebrae with loss of the disc space is highly suggestive of spinal osteomyelitis. Gallium not only enhances the specificity of the diagnosis but provides information about surrounding soft tissue infection. In the diabetic foot, labeled leukocyte imaging alone is sufficient to determine the presence of osteomyelitis in the fore--foot. In the midfoot and hindfoot it may be necessary to combine leukocyte scintigraphy with bone scintigraphy to precisely localize the infection. Labeled leukocytes accumulate in the uninfected neuropathic joint and preliminary data suggest that leukocyte/marrow imaging may be useful to determine the significance of such uptake. For the painful joint replacement, if infection is the primary concern, leukocyte/marrow scintigraphy should be performed initially. If any postoperative complication, regardless of type, is the concern, it is reasonable to begin with bone scintigraphy because a normal study rules strongly against any complication. An abnormal bone scan will require additional studies to more precisely determine the cause of that abnormality.

Bone and Bones↗

SPECT and subtraction imaging of an ectopic parathyroid adenoma.

Primary hyperparathyroidism is a disease best managed surgically; resection of the lesion(s) is curative. Although the routine use of localizing procedures is controversial before surgery, it is generally agreed that these techniques are useful in cases of reexploration. The authors have recently studied a patient with long-standing hyperparathyroidism, in whom initial surgery was unsuccessful. Although planar imaging with Tc-99m sestamibi is usually sufficient for identification and localization of the lesion, both SPECT and subtraction imaging provided additional information that contributed to the success of the subsequent surgery. Single-proton emission computed tomography provided critical information about the position of the ectopic parathyroid adenoma in relation to the right submandibular salivary gland, whereas subtraction imaging confirmed that the focus was indeed a parathyroid lesion, and not merely an anatomic variant of a normal salivary gland.

Adenoma↗