The importance of delayed imaging in the study of hepatoma with a new hepatobiliary agent

Concentration of Tc-99m(Sn)-N-pyridoxyl-5-methyltryptophan (Tc-99m PMT), a biliary agent, in hepatic tumors was studied with delayed hepatobiliary imaging in 23 patients with histologically verified hepatocellular carcinomas. All 23 showed filling defects on liver images obtained with Tc-99m tin colloid. In the images taken 5 hr after Tc-99m PMT injection, ten cases showed increased uptake in the carcinoma, six nearly normal uptake, and seven decreased uptake. In those showing the increased uptake of Tc-99m PMT in the tumor, the ratio of the radioactivity in the lesion to that in the adjacent liver parenchyma (T/L ratio) increased progressively with time for 5 hr after injection. These results indicate that delayed Tc-99m PMT images, obtained 5 hr after injection, are useful in assessment of uptake of the radioactivity by hepatocellular carcinoma.     

In vitro properties andin vivo behavior of technetium-99m labeled fibrinogens

Fibrinogen was labeled with Tc-99m by two methods and thein vitro stability andin vivo behavior in mice were studied. The Tc-99m labeling was performed by mixing an unreduced fibrinogen (UnFib) or a reduced fibrinogen (ReFib) with Tc-99m pertechnetate in the presence of stannous chloride. In both of them, chelation with Tc-99m resulted in a single radiochemical product. For thein vitro stability studies, Tc-99m labeled fibrinogen (Tc-99m UnFib) was prepared with UnFib, and transchelation with cysteine solution was easy to produce compared to Tc-99m labeled fibrinogen (Tc-99m ReFib) prepared with ReFib. The radioactivity bound to clottable protein for Tc-99m UnFib and Tc-99m ReFib was about 70% and about 69%, respectively. Thein vivo behavior of these labeled fibrinogens was studied, and their efficiencies for imaging an abscess and Ehrlich tumor in mice were determined with a gamma camera. Technetium-99m UnFib underwent a rapid partial exchange of the Tc-99m with compounds of the blood buffer systemin vivo, resulting in early urinary excretion. On the other hand, the fraction of Tc-99m ReFib that remained intactin vivo was biologically active and would be incorporated into the abscess and tumor. The uptake in the abscess increased slightly over time with Tc-99m ReFib, but the abscess to blood and abscess to muscle ratios were 0.09 and 2.6 at 5 hr, respectively. Clearly delineated images of the abscess were obtained beginning at about 5 hr after injection. The tumor to blood and tumor to muscle ratios were 0.05 and 1.4 at 5 hr, respectively. The Ehrlich tumor image in mice was slightly visible at 10 hr. The short half-life of Tc-99m was inappropriate for fibrinogen with a low pharmacokinetic value, because it was necessary for imaging of the abscess and tumor to take a long time.     

Correlation between P-glycoprotein (P-gp) expression in parathyroid and Tc-99m MIBI parathyroid image findings

The major factor to influence localization of parathyroid adenomas is tumor size. P-glycoprotein (P-gp) expression in parathyroid adenomas has been considered to be an another possible factor to influence localization of parathyroid adenomas because false-negative studies have been reported with large tumors and true-positives reported with very small tumors in previous studies. The aim of this study was to characterize Tc-99m MIBI uptake and retention by parathyroid adenomas and to correlate this with cell surface expression of P-gp. Sixteen patients with parathyroid adenoma (larger than 1.5 gm) underwent dual-phase (10min and 2hr) Tc-99m MIBI parathyroid image immediately before parathyroid exploration. Tissues were obtained from normal and abnormal parathyroid glands and from the thyroid gland. Immunohistochemistry (IHC) was obtained with monoclonal antibodies to identify P-gp expression in all tissues. All of the 16 parathyroid adenomas and 32 normal control specimens (16 normal parathyroid and 16 normal thyroid specimens) were submitted for P-gp detection by IHC. The dual-phase Tc-99m MIBI parathyroid image accurately localized 14 parathyroid adenomas, but not the remaining 2 adenomas. The 14 parathyroid adenomas with significant Tc-99m MIBI uptake in delayed 2hr images revealed negative P-gp expression, but the 2 adenomas without significant Tc-99m MIBI uptake, as well as normal parathyroid and normal thyroid specimens, revealed positive P-gp expression when evaluated by IHC. Not only the size of parathyroid adenomas, but also significant P-gp expression limited the sensitivity of dual-phase Tc-99m MIBI parathyroid image to localize parathyroid adenomas before operation.     

Tc-99m antifibrin Fab' fragments for imaging venous thrombi: evaluation in a canine model

An antifibrin antibody (T2G1s) Fab' fragment labeled with technetium-99m was tested for its ability to produce images of fresh thrombi in dogs. In gamma camera images, all thrombi were evident by 2-4 hours after injection. Mean thrombus-to-blood and thrombus-to-muscle ratios averaged 4.0 and 69 at four hours after injection and increased to 24 and 270, respectively, by 24 hours after injection. When compared with I-125 fibrinogen injected into the same dogs, Tc-99m-antifibrin Fab' had lower absolute uptake in thrombus but higher thrombus-to-blood ratios due to a faster rate of disappearance from the blood. The primary route of excretion was through the kidneys. Tc-99m-antifibrin Fab' was highly stable in vivo, with an average of 82% of the circulating radioactivity able to bind to fibrin at 4 hours after injection. When compared with an In-111-labeled Fab fragment of antifibrin antibody 59D8, thrombus-to-blood and thrombus-to-muscle ratios were slightly higher for the Tc-99m-labeled antibody, and the blood disappearance rate was slightly faster. The absolute uptake in thrombus, however, was not significantly different, and the thrombus was visualized at about the same time after injection. These studies suggest that Tc-99m T2G1s Fab' is a potential agent for detecting thrombi in a clinical setting.     

Simple procedure for red blood cell labeling with Tc-99m HMPAO. Preliminary clinical results.

Clinical applications for Tc-99m HMPAO labeled red blood cells have not been previously reported. The authors describe a simple, aseptic, closed, one-step centrifugal procedure for red blood cell labeling with Tc-99m HMPAO and isolation from whole blood, and they report the preliminary results of using these labeled red blood cells to detect acute gastrointestinal bleeding in 11 patients. Whole blood was radiolabeled with Tc-99m HMPAO preparation and blood cells were separated by centrifugation (30 min, 200 g, 20 degrees C) using Polyprep density gradient medium. Red blood cells contained about 50% of the radioactivity. Four out of the 11 patients imaged with a gamma camera after reinjection of labeled autologous red blood cells showed abnormal accumulation, suggesting gastrointestinal bleeding that was verified at surgery and was at the site of abnormal activity in all cases. Image quality with Tc-99m HMPAO was comparable to that of Tc-99m pertechnetate labeled pretinned red blood cells. Tc-99m HMPAO can be used as a red blood cell labeler; however, its elution rate from red blood cells limits its applicability in some investigations.     

In vivo distribution of Tc-99m labeled recombinant tissue-type plasminogen activator in control and thrombus-bearing rats

In vivo distribution of Tc-99m labeled recombinant tissue-type plasminogen activator (Tc-99m-rt-PA) was studied in control rats and thrombus-bearing rats. To compare fibrin binding in vivo with that in vitro, Tc-99m-rt-PA binding to fibrin gel in vitro was also imaged. Rapid blood clearance and accumulation into the liver and kidneys were observed in both control and thrombus-bearing rats. Accumulation in the stomach, which indicates instability of labeled rt-PA in vivo, was very low until two hours after injection. Tc-99m-rt-PA accumulation in the clots was higher than that in skeletal and heart muscles, although it was lower than in blood, liver, and kidneys. Administration of aprotinin, an antifibrinolytic agent, significantly prolonged clot accumulation of Tc-99m-rt-PA at 30 minutes after injection. These results suggest that fibrinolysis is responsible for the low rt-PA concentration in the clots. A scintigram of a thrombus-bearing rat demonstrated increased radioactivity at the clot forming site. On the other hand, Tc-99m-labeled human albumin, which was used as a control, was not accumulated in the clot. Tc-99m-rt-PA binding to fibrin gel in vitro was clearly imaged. By comparison, in vivo fibrin binding of Tc-99m-rt-PA was much lower than in vitro. The reasons for low thrombus uptake in vivo may be: 1. biochemical inactivation of extrinsically administered rt-PA by t-PA inhibitor. 2. fibrinolysis by rt-PA activated plasminogen. Overcoming these limitations will enable Tc-99m-rt-PA to reach the stage of clinical trials.     

Technetium-99m serum albumin measurement of gastrointestinal protein loss in a subtotal gastrectomy patient with giant hypertrophic gastritis

Gastrointestinal protein loss was measured using Tc-99m labeled human serum albumin in a patient with giant hypertrophic gastritis. Gastric secretion was aspirated via a nasogastric tube and measured for radioactivity after intravenous injection of Tc-99m albumin. Assessment of radioactivity of the collected gastric secretion yielded a total radiocount of 98.7 kilocounts per minute within 6 hours, which is equivalent to 1.1% of the total dose. Therefore, at least 1.1% of the circulating albumin was excreted into the gastric cavity within 6 hours, and, since simultaneous abdominal imaging did not demonstrate obvious accumulation of tracer in the gastrointestinal tract, protein loss was thought to be due to giant gastric rugae of the resected stomach. It was concluded that Tc-99m albumin is a valuable means for detection of the site of protein loss in patients with protein-losing gastroenteropathy. This method has several advantages in the clinical setting; it is less time consuming, easy to perform, and provides quantitative and qualitative assessment of protein loss.     

Tc-99m HMPAO labeled donor leukocyte scan in liver transplant

Tc-99m HMPAO labeled donor leukocytes were used to image the focus of an hepatic infection in a 32-year-old liver transplant patient. Six hours after the administration of labeled leukocytes, radioactivity accumulation was detected in the liver suggesting an intrahepatic infection focus. Diagnosis of infection was confirmed at surgery.     

Assessment of intra-arterial injected autologous bone marrow mononuclear cell distribution by radioactive labeling in acute ischemic stroke

OBJECTIVE: To evaluate the feasibility of monitoring the autologous mononuclear bone marrow (ABMMN) cells implanted into the brain after acute ischemic stroke by the technique of labeling with Tc-99m-HMPAO. CASE REPORT: A 37-year-old man presented with aphasia, right-side hypoesthesia, and right homonymous hemianopsia after an acute ischemic stroke of the left middle cerebral artery. He was included in an autologous bone marrow mononuclear cell-based therapy research protocol about the safety of intra-arterial autologous bone marrow mononuclear cell transplantation for acute ischemic stroke. Nine days after the stroke he received 3.0 x 10(7) ABMMN cells delivered into the left cerebral middle artery via a balloon catheter. Approximately 1% of these cells were labeled with 150 MBq (4 mCi) Tc-99m by incubation with hexamethylpropylene amine oxime (HMPAO). RESULTS: Brain perfusion images with Tc-99m ECD demonstrated hypoperfusion in the left temporal and parietal regions. The perfusion brain images were compared with tomographic views of the brain obtained 8 hours after ABMMN-labeled cell delivery, revealing intense accumulation of the ABMMN-labeled cells in the ipsilateral hemisphere. A whole-body scan was done and showed left brain, liver, and spleen uptake. CONCLUSIONS: Our results showed that Tc-99m HMPAO can be used to label ABMMN cells for in vivo cell visualization, and that brain SPECT imaging with labeled ABMMN cells is a feasible noninvasive method for studying the fate of transplanted cells in vivo. Additionally, our findings demonstrate the localization of these intra-arterially injected cells.     

Preliminary findings in the evaluation of hepatic malignancies by radioimmunodetection, X-ray computed tomography, and magnetic resonance imaging

In 12 consecutive patients with suspected metastatic carcinoma of the liver, we evaluated the sensitivity of radiolabeled antibodies to tumor antigens, magnetic resonance imaging, and X-ray computed tomography imaging in the detection of hepatic malignancies. Studies were performed with 131I labeled antibodies to CEA and/or CSAp; polyclonal, monoclonal and F(ab')2 antibodies were used. Nontarget radioactivity was diminished by administration of 99mTc reagents simulating nontumor distribution and use of a computer subtraction method. In nine patients with confirmed liver neoplasms, radioimmunodetection disclosed the foci of hepatic malignancies. In three patients with suspected liver neoplasms, the antibody studies were positive, but at this time have not been confirmed. X-ray computed tomography each disclosed mass lesions in five patients and magnetic resonance in three. These findings suggest that radioimmunodetection provides greater accuracy in the detection and localization of cancer than other diagnostic modalities currently used.     

Dual isotope scanning with gallium-67 citrate and technetium-99m radiopharmaceuticals

The interpretation of Ga-67 scans is limited by the complex anatomic and physiologic distribution of Ga-67 and by the low resolution possible with this isotope. The use of a second isotope Tc-99m, tagged to an appropriate pharmaceutical allows the identification of anatomic landmarks. Computer acquisition of both the Ga-67 and Tc-99m images allows for subtraction of the Tc-99m images from the Ga-67 images and leads to precise localization of abnormal Ga-67 accumulations. Only a small percentage of the counts in the Tc-99m window are due to Ga-67 scatter and do not degrade the Tc-99m images. Cases illustrating the value of the dual-isotope technique are presented.     

Optimal pinhole techniques for preoperative localization with Tc-99m MIBI for primary hyperparathyroidism.

PURPOSE: Technetium-99m-labeled 2-methoxyisobutylisonitrile (Tc-99m MIBI) has been used extensively to localize parathyroid adenomas before operation. Imaging techniques vary widely, and the aim of this study was to determine the optimal time of delayed imaging and the value of routine correlative pertechnetate thyroid imaging. MATERIALS AND METHODS: In this study, preoperative parathyroid localization was performed using pinhole anterior and oblique images (15 minutes and 2 and 4 hours after injection) with correlative pertechnetate thyroid images. Ninety-seven patients underwent dual- or triple-phase Tc-99m MIBI imaging and correlative pertechnetate thyroid imaging before surgery. Two nuclear medicine physicians blinded to the surgical findings interpreted all available images and various Tc-99m MIBI image combinations at 15 minutes alone; 15 minutes and 2 hours, 15 minutes and 4 hours; and 15 minutes and 2 and 4 hours each with and without correlative pertechnetate thyroid imaging. RESULTS: Ninety parathyroid adenomas were detected in 86 patients. The optimal results were achieved with 15-minute and 2- and 4-hour Tc-99m-MIBI images, with correlative thyroid scans resulting in a sensitivity rate of 88%. Fifteen-minute and 2-hour Tc-99m-MIBI images and correlative thyroid scans and 15-minute and 4-hour Tc-99m MIBI images and correlative thyroid scans produced similar results (sensitivity rate, 86% and 83%, respectively; P = not significant). Compared with all Tc-99m MIBI image combinations alone, the addition of the routine correlative thyroid scan significantly improved sensitivity and also improved reporter confidence in 45% of studies. CONCLUSIONS: Of the pinhole techniques compared, 15-minute and 2-hour Tc-99m MIBI images with correlative thyroid scanning may be the preferred imaging protocol, because this yields results similar to imaging for as long as 4 hours after injection in a shorter, more logistically acceptable imaging time.     

Axillary lymphoscintigraphy by radioimmunodetection of carcinoembryonic antigen in breast cancer

In seven women with carcinoma of the breast I-131-labeled antibodies to carcinoembryonic antigen (CEA) were administered subcutaneously in the finger webs. Subsequent scintigraphic immages demonstrated localization of radioactivity in the ipsilateral axillary metastases of all patients and in the contralateral axillae of three. Fifteen patients with either gastrointestinal or genitourinary cancers were studied as controls; in 12 both the hands and feet were injected with antibodies to CEA and in the other three either the hands or feet. Radioactivity was observed in the inquinal nodes of four control patients with tumors below the diaphragm and in the axillary nodes of one patient with a tumor above the diaphragm. The concentration of antibody in lymph node metastases from breast carcinoma was 100% specific. In those lymph nodes that presumably contained no metastatic tumor but demonstrated localization of labeled antibody, retention of CEA in the nodes from tumor drainage is postulated as the receptor site for the antibody.     

Increased activity on immediate phase of bone imaging does not always indicate increased blood volume

The immediate Tc-99m MDP image of a neoplastic right wrist mass in a 10-year-old boy demonstrated intense focal accumulation that suggested a very vascular tumor, but delayed images showed only slightly increased activity in the mass. A Tc-99m labeled RBC study was performed to permit whole-body blood pool imaging for other vascular lesions, and it did not demonstrate an increased blood volume in the mass. Biopsy showed the tumor to be a Ewing's sarcoma, probably of soft tissue origin. The sarcoma was not very vascular. The intense immediate accumulation of Tc-99m MDP in this case may be attributed to increased microvascular permeability.     

A technique for the preparation of Tc-99m red blood cells for evaluation of gastrointestinal hemorrhage

Tc-99m labeled red blood cell (RBC) preparations are gaining wide acceptance in the diagnosis and localization of gastrointestinal bleeding. A major requirement of the radiopharmaceutical is that the percentage of Tc-99m attached to red cells in the injected dose must be extremely high, since free pertechnetate is secreted into the gastrointestinal tract and may obscure a bleeding site. We have developed a combined in vivo/in vitro labeling procedure which is simple and rapid, and which enables the administration of substantial amounts of RBC-bound Tc-99m and minimizes the amount of unbound technetium present. The technique is readily utilizable in any nuclear medicine clinic and requires no investigative pharmaceuticals.     

Analogy between tumor uptake of technetium(V)-99m dimercaptosuccinic acid (DMSA) and technetium-99m-MDP

Sixty patients with a variety of malignant tumors were examined with Tc-99m(V) dimercaptosuccinic acid (DMSA) prepared by modification of a commercially available DMSA kit. Significant uptake of Tc-99m(V)-DMSA was observed in a number of tumors, offering additional clinically useful information. In the majority of cases in this study, however, the benefit of the Tc-99m(V)-DMSA image was limited because of low sensitivity. The most striking observation was the similarity between the tumor concentration of Tc-99m(V)-DMSA and the Tc-99m-MDP uptake in the tumor on the regular bone image. Therefore, patients with Tc-99m-MDP uptake in nonosseous tumor sites on the bone scan may be suitable candidates for tumor imaging with Tc-99m(V)-DMSA.     

Computerized double-tracer subtraction scanning with gallium-67 citrate in inflammatory diseases.

A gallium-67/technetium-99m subtraction technique was used with a variable weighting factor. That is, each image was separately set to 100%. Varying amounts of the Tc-99m images were subtracted from those of Ga-67. A total of 95 patients who had radiogallium scanning for suspected inflammatory disease were studied by the subtraction technique. Thirty of these patients had abnormal Tc-99m pyrophosphate bone scans, while 20 had abnormal radiogallium abdominal foci; 45 had defects in liver, spleen, or kidney images. The subtraction technique with variable weighting was highly successful in enhancing hot-spot visibility, and in providing information as to the anatomic location of the defect.     

Acid-citrate-dextrose compared with heparin in the preparation of in vivo/in vitro technetium-99m red blood cells

Red blood cells labeled in vivo/in vitro with Tc-99m (Tc-99m RBC) were prepared in a series of 21 patients and two normal volunteers. In each subject both heparin and acid-citrate-dextrose (ACD) solutions were used to label tandem blood samples. The immediate preinjection binding efficiency (BE) was then determined. In each of the 23 studies, the ACD preparation yielded superior BE. The average BE was 93.47% (+/- 3.78) with ACD and 87.23% (+/- 4.29) with heparin. With the ACD method the effect of carrier Tc-99 may be as great as a 24% reduction in BE observed when initial eluates from long-ingrowth-time generators were used. Improved image quality with minimal renal and urinary-bladder activity results with ACD labeling. It is concluded that the use of ACD results in superior RBC labeling with less nontarget activity relative to heparin and is preferred over heparin for preparing in vivo/in vitro Tc-99m RBC.     

Brown tumor of the sternum: a potential source of false-positive Tl-201 and Tc-99m subtraction imaging in the mediastinum

Tl-201 and Tc-99m subtraction imaging is a well-established technique for detecting parathyroid adenomas. We report a case of a brown tumor of the upper sternum mimicking an ectopic mediastinal parathyroid adenoma on Tl-201 and Tc-99m subtraction imaging in a patient with hyperparathyroidism. This brown tumor showed Tl-201 uptake but not Tc-99m uptake and thus did not subtract out in this scan.     

Technetium-99m labeled RBC imaging in gastrointestinal bleeding from gastric leiomyoma

Tc-99m labeled RBC imaging is becoming increasingly useful in detecting gastrointestinal (GI) bleeding sites. A patient is presented who had massive GI bleeding from an unsuspected gastric leiomyoma in whom a Tc-99m sulfur colloid GI bleed image was negative. The Tc-99m labeled RBC imaging done on the day after sulfur colloid imaging revealed increased gastric activity due to active bleeding from an intragastric leiomyoma. Tc-99m labeled RBC imaging helped in early detection of the bleeding site resulting in its successful treatment. This experience also reinforces the assertion that Tc-99m labeled RBC imaging may be more helpful than Tc-99m sulfur colloid imaging in patients with upper GI or intermittent bleeding.