Tc-99m hexamethylpropylene amine oxime scintigraphy in the diagnosis of brain death and its implications for the harvesting of organs used for transplantation.

PURPOSE: Diagnosing brain death is important in managing the comatose patient for whom the continuation of life support is being questioned and when organ harvesting is being considered. The virtual immediate localization of Tc-99m HMPAO to cerebral and cerebellar tissue provides an index of blood perfusion, and its absence denotes brain death. Other methods for assessing brain death include cerebral angiography, MRI, CT imaging after inhalation of stable xenon, electroencephalography, and clinical examination. The contrast material used for angiography may damage harvested organs, and the other studies have significant errors. MRI, CT imaging, and angiography are unsuitable for bedside use. METHODS: Twenty-three patients, who presented with head trauma, prolonged anoxia or intrinsic brain disease (e.g., glioblastoma multiforme) and who were brain-dead by clinical examination criteria, were referred to the nuclear medicine division for verification of brain death. For adults, approximately 25 mCi Tc-99m hexamethylpropylene amineoxime (HMPAO) was administered intravenously. All patients but one were imaged using a mobile scintillation camera at the bedside. RESULTS: We demonstrated (1) both cerebral and cerebellar perfusion, (2) neither cerebral nor cerebellar perfusion, (3) cerebral without cerebellar perfusion, and (4) cerebellar without cerebral perfusion. Patients without cerebral perfusion were diagnosed as brain-dead. The significance of a viable cerebellum in the absence of cerebral viability was not fully appreciated, although organs were harvested from such patients. We determined how well the clinical examination criteria held up in the diagnosis of brain death against the new gold standard of Tc-99m HMPAO scintigraphy: Clinical examination criteria correctly predicted brain death only 83% of the time compared with HMPAO scintigraphy. CONCLUSIONS: Brain death assessment by Tc-99m HM-PAO scintigraphy has proved to be a reliable, safe, and cost-effective bedside method and may have practical application in the assessment of brain death in potential cadaveric donors.

I-131 orthoiodohippurate assessment of renal function after heart transplantation.

PURPOSE: The authors studied the relation between cardiac output (CO) and effective renal plasma flow (ERPF) and compared values from control patients with various cardiac problems with those in a group of study patients who had undergone heart transplantation. METHODS: The experimental group was divided into three subgroups according to the interval between the time of surgery and the time of the CO-ERPF studies. Group 1 consisted of patients studied fewer than 10 days after surgery; group 2 consisted of patients studied 10 to 20 days after operation; and group 3 consisted of patients studied more than 20 days after operation. Effective renal plasma flow was determined by the single-injection, single plasma sample method, where 50 microCi I-131 orthoiodohippurate was injected intravenously in a single dose and plasma concentrations of radioactivity were determined. The quotient of injected dose radioactivity divided by plasma radioactivity is highly predictive of global ERPF. Cardiac output was measured by thermodilution. RESULTS: In the control group, a positive linear correlation was found between CO and ERPF; however, the CO:ERPF ratio was elevated, and after heart transplantation, a lag time was observed for as long as 3 weeks in some patients before CO:ERPF ratios returned to control group levels. The regression equation and standard error for the control group was CO = 1.85 + 0.0065 ERPF (+/-0.62) l/min versus 1.433 + 0.0068 ERPF (+/-0.64) l/min for group 3. The correlation coefficients comparing CO with ERPF were r = 0.88, 0.23, 0.51, and 0.85, for the control group and groups 1, 2, and 3, respectively. CONCLUSION: A localized release of catecholamines from the adrenal gland is proposed to cause ERPF damping after abrupt increases in CO.

In-111 monoclonal antibody versus Ga-67 citrate and Tc-99m SC subtraction in a patient with malignant melanoma.

Gallium-67 is routinely used for follow-up of patients with malignant melanoma. However, its nonspecificity for melanoma and its high rate of false-positive results have always been a matter of concern. The authors describe a patient who encountered serious problems with the use of gallium. Because gallium is taken up well by the liver and by melanoma, results of gallium scintigraphy of the liver may appear normal even if there is metastatic disease. In this patient, results of gallium scintigraphy of the liver were negative for metastasis but revealed extrahepatic foci detected by the monoclonal antibody. Computed tomography showed areas of attenuation, revealing only a few intrahepatic tumors and no extrahepatic disease. Tc-99m SC revealed intrahepatic metastases, but no extra-hepatic metastases were seen. A monoclonal antibody (ZME-018) scintigram did reveal hepatic metastases along with probable small, extrahepatic, metastatic foci. Overall hepatic uptake of the monoclonal antibody was relatively low. An image subtraction algorithm was devised whereby the sulfur colloid image was subtracted from the gallium scintigram. The resultant image revealed both the intrahepatic and extrahepatic metastases seen on the ZME-018 images. It is likely that in the past many hepatic metastases have been missed because Tc-99m SC images have not been routinely used as part of melanoma management protocols. The uptake of the ZME-018 by the tumor was significantly higher than that of the normal liver, suggesting that ZME-018 labeled with the appropriate emitter may be an effective specific therapeutic tool in selected patients.

Thallium-201/technetium-99m-phytate (colloid) subtraction imaging of hepatocellular carcinoma.

UNLABELLED: This paper evaluates the clinical usefulness of 201Tl to image hepatocellular carcinoma (HCC), using 201Tl, 99mTc-phytate (colloid) and a three-headed SPECT camera. METHODS: The tumor-to-nontumor ratios (T/N) of 201Tl for different categories of HCC were generated. Tumors were emphasized by image subtraction (201Tl-99mTc-colloid). Thirty-three lesions in 16 patients (18 studies) with HCC were evaluated. There were 19 untreated nodular, five untreated diffuse, five local recurrent and four necrotic lesions after interventional therapy. RESULTS: The mean T/N were as follows: untreated nodular 1.54 +/- 0.31 (mean +/- s.d.), untreated diffuse 1.28 +/- 0.26, local recurrence 1.50 +/- 0.29 and necrosis 0.22 +/- 0.06. All the tumors (except necrotic areas) were enhanced by the image subtraction. CONCLUSION: Thallium-201 is useful for liver tumor imaging but 99mTc-phytate (colloid) is essential to discriminate 201Tl tumor uptake from normal liver accumulation. Image subtraction (201Tl/99mTc-colloid) is helpful in detecting HCC.

Colorectal carcinoma metastases: detection with In-111-labeled monoclonal antibody CCR 086.

A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

Radioimmunoimaging of metastatic medullary carcinoma of the thyroid gland using an indium-111-labeled monoclonal antibody to CEA.

Elevated levels of carcinoembryonic antigen (CEA) or calcitonin after surgical therapy for medullary carcinoma of the thyroid gland (MCT) indicate the presence of residual or metastatic disease. CEA elevations appear to be prognostically more reliable in patients with metastatic disease and suggest a more virulent tumor. Attempts to stage the disease with use of conventional imaging techniques are usually inadequate, as is the therapy for disseminated or recurrent MCT. An indium-111-labeled anti-CEA monoclonal antibody (ZCE-025) was used to image metastases in a patient with MCT. Potential applications of monoclonal antibody technology in the management of MCT would include (1) preoperative differentiation of unicentric from multicentric thyroid gland involvement, (2) detection of regional or distant metastases or both, (3) measurement of response to systemic therapy, and (4) the facilitation of radionuclide immunoconjugate therapy.

Distinguishing avascular necrosis from segmental impaction of the femoral head following an acetabular fracture: preliminary report.

To distinguish segmental impaction from avascular necrosis of the femoral head, 26 consecutive patients who sustained an acute displaced acetabular fracture were assessed preoperatively with routine radiographs, computed tomography, and radionuclide imaging using pinhole collimation and single photon emission computed tomography (SPECT). The diagnostic criterion for avascular necrosis was a photopenic defect of the femoral head, whereas, the criterion for segmental impaction was an area of impaction of at least 1 cm2 noted at the time of surgery. Of this series, 3 incurred a segmental impaction while 1 showed evidence consistent with avascular necrosis on SPECT imaging. None of the patients possessed diagnostic features of both complications. The distinction between these two complications of an acetabular fracture should contribute to the application of appropriate surgical techniques to correct segmental impaction and avascular necrosis.

Results of radionuclide assessment of cardiac function following transplantation of the heart.

Radionuclide assessment of ejection fraction was determined early and late postoperatively following cardiac transplantation in 16 patients. In 11 patients, ejection fraction was determined within 48 hours of an endocardial biopsy. There was no relationship between the severity of histologically evident rejection and the ejection fraction (Pearson correlation coefficient [r] = -0.11; p = 0.47). In 2 patients, severe graft fibrosis developed with consequent diminution in ejection fraction. There was no relationship between severity and duration of rejection or the amount of immunosuppression required to treat acute rejection and the development of graft fibrosis. The mean resting ejection fraction in 7 patients in follow-up ranging from 6 to 21 months after transplantation was 0.59 +/- 0.06 (standard deviation), and the mean exercise ejection fraction in 6 of these patients was 0.72 +/- 0.08. Radionuclide-determined ejection fraction is not predictive of rejection early after operation. During short-term late follow-up, systolic left ventricular function at rest and exercise has been retained at normal levels.

Diagnosis of impaired renal function after kidney transplantation using renal scintigraphy, renal plasma flow and urinary excretion of hippurate.

The use of 131I-orthiodohippurate (OIH) scintigraphy combined with the estimated renal plasma flow (ERPF) and excretion index (EI) has been beneficial in separating impaired renal function due to graft rejection from acute tubular necrosis, ureteral obstruction, urinary extravasation and in some instances renal artery occlusion. The radionuclide data accurately identified acute and chronic rejection, confirmed by the clinical course, increase in BUN and serum creatinine and on occasion renal biopsy. Reversible and irreversible acute tubular necrosis (ATN) were clearly differentiated from acute rejection. When the ERPF and EI were plotted on a graph, multiple sequential radionuclide studies accurately predicted graft survival when chronic rejection existed. The limitation of this technique was the inability to discriminate between renal artery stenosis, ureteral obstruction and inflammatory disease. Scintigraphic studies did not distinguish between renal artery stenosis and chronic rejection. In these circumstances arteriography was the diagnostic procedure of choice. Although ureteral obstruction often can be correctly diagnosed by scintigrams, the ERPF, EI and intravenous pyelogram remained the most accurate diagnostic procedures. Recurrent glomerulonephritis, gram negative septicemia and generalized viral illness (herpes zoster or cytomegalovirus) simulated acute rejection and had to be separated by renal biopsy or the clinical course. The most valuable features of the radionuclide technique included: 1) the noninvasive method, 2) the simplicity, 3) the rapidity and 4) the reproducibility.

Renal autotransplantation using hypothermic storage and pulsatile perfusion.

Three patients with severe hypertension secondary to renal artery stenosis were treated by renal autotransplantation. Of these 3 patients 2 had solitary kidneys and 1 had 2 renal arteries to each kidney, all of which were stenosed. Renal autotransplantation with hypothermia of the kidney was performed in all 3 patients rather than the more conventional arterial bypass or endarterectomy because 1) hypothermic preservation permitted a prolonged ischemia time and 2) there was improved exposure for the vascular anastomosis. Postoperatively 2 patients remained normotensive without drugs for 9 and 12 months and 1 patient died of septicemia not directly related to the autotransplant. All 3 patients required expansion of the intravascular volume postoperatively to overcome the loss of vasoconstrictor substances following restoration of renal blood flow.