Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Dobutamine-atropine stress echocardiography and dipyridamole sestamibi scintigraphy for the detection of coronary artery disease: limitations and concordance.

OBJECTIVES: We sought to compare dobutamine-atropine stress echocardiography (DASE) and dipyridamole Technetium 99-m (Tc-99m) sestamibi single photon emission computed tomography (SPECT) scintigraphy (DMIBI) for detecting coronary artery disease (CAD). BACKGROUND: Both DASE and DMIBI are effective for evaluating patients for CAD, but their concordance and limitations have not been directly compared. METHODS: To investigate these aims, patients underwent multistage DASE, DMIBI and coronary angiography within three months. Dobutamine-atropine stress echocardiography and stress-rest DMIBI were performed according to standard techniques and analyzed for their accuracy in predicting the extent of CAD. Segments were assigned to vascular territories according to standard models. Angiography was performed using the Judkin's technique. RESULTS: The 183 patients (mean age: 60 +/- 11 years, including 50 women) consisted of 64 patients with no coronary disease and 61 with single-, 40 with two- and 18 with three-vessel coronary disease. Dobutamine-atropine stress echocardiography and DMIBI were similarly sensitive (87%, 104/119 and 80%, 95/119, respectively) for the detection of CAD, but DASE was more specific (91%, 58/64 vs. 73%, 47/64, p < 0.01). Sensitivity was similar for the detection of CAD in patients with single-vessel disease (84%, 51/61 vs. 74%, 45/61, respectively) and multivessel disease (91%, 53/58 vs. 86%, 50/58, respectively). Multiple wall motion abnormalities and perfusion defects were similarly sensitive for multivessel disease (72%, 42/58 vs. 66%, 38/53, respectively), but, again, DASE was more specific than DMIBI (95%, 119/125 vs. 76%, 95/125, respectively, p < 0.01). Dobutamine-atropine stress echocardiography and DMIBI were moderately concordant for the detection and extent of CAD (Kappa 0.47, p < 0.0001) but were only fairly (Kappa 0.35, p < 0.001) concordant for the type of abnormalities (normal, fixed, ischemia or mixed). CONCLUSIONS: Dobutamine-atropine stress echocardiography and DMIBI were comparable tests for the detection of CAD. Both were very sensitive for the detection of CAD and moderately sensitive for the extent of disease. The only advantage of DASE was greater specificity, especially for multivessel disease. Dobutamine-atropine stress echocardiography may be advantageous in patients with lower probabilities of CAD.

Long-term intravenous antibiotic therapy in chronic osteomyelitis.

Because the optimal treatment of chronic osteomyelitis is not well established, we studied the efficacy of prolonged (three months or more) outpatient intravenous antibiotic therapy via a Hickman catheter. Seventeen patients were entered into our protocol (13 with chronic osteomyelitis, three with chronic septic arthritis, and one with subacute osteomyelitis). Pseudomonas aeruginosa was the most common bone isolate, followed by Staphylococcus aureus. Most patients had polymicrobial isolates. Patients were followed up with clinical examinations, serial measurements of erythrocyte sedimentation rate, and scans using technetium Tc 99m medronate and gallium citrate Ga 67. Of the ten patients with chronic osteomyelitis who completed therapy, eight were considered cured. After further follow-up, three of the cured patients had recurrences requiring additional therapy.

Comparison of single-photon emission computed tomography with [123I]iodoamphetamine and xenon-enhanced computed tomography for assessing regional cerebral blood flow.

Regional CBF (rCBF) images obtained from xenon-enhanced computed tomography (XeCT) and single-photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (IMP) done with a rotating gamma-camera were compared in nine patients. Both XeCT and SPECT/IMP demonstrated flow abnormalities at all sites of infarction identified by CT, while detecting reduced rCBF in areas normal by CT in eight of the nine patients. All areas that were abnormal on XeCT were abnormal on the comparable SPECT/IMP images. The major advantages of XeCT are its greater resolution and potential for noninvasive quantitation of rCBF, while the major advantage of SPECT/IMP is its visualization of the entire brain on transverse, coronal, and sagittal sections.

Current imaging strategies for colorectal cancer.

Endoscopy and barium enema examinations are used to identify the primary site of disease in patients with clinical suspicion of colorectal cancer. Once colorectal cancer has been confirmed by imaging studies and biopsy, preoperative evaluation is directed toward accurate disease staging. Most currently available imaging techniques are inaccurate for detecting transmural extension, perienteric spread of tumors and distant lymph node involvement. Although both computed tomography (CT) and magnetic resonance imaging (MRI) have an unacceptably low sensitivity for accurate staging, CT is clearly superior to MRI for detecting extrahepatic metastases. Transrectal ultrasonography, however, is a promising new method for detecting perirectal spread of disease. The diagnostic efficacy of MRI and intravenous dynamic hepatic CT for detecting liver metastases is approximately equal. CT during arterial portography is recommended before resection of solitary liver metastases. Chest radiography is also part of the routine preoperative evaluation. Bone scans are rarely performed in patients without the skeletal pain suggestive of bone metastases. During the years following surgery for colorectal cancer, many patients undergo special imaging studies to identify local tumor recurrence, secondary tumor growth elsewhere within the large bowel and both regional and distant spread of disease. Thus, for the patient with a sharply increasing carcinoembryonic antigen level, CT of the abdomen and liver is the current recommendation. Immunoscintigraphy is a new imaging modality that addresses some of the limitations of current diagnostic procedures for colorectal cancer. This procedure gives whole body information on disease extent, especially in the extrahepatic abdomen and pelvis, and can therefore contribute to patient management decisions.

Bone scintigraphy: Part 2. Orthopedic bone scanning.

Bone scanning provides a functional assessment of skeletal pathology not available with conventional radiography or special radiographic techniques such as CT and MRI. Bone scanning detects osteoblastic activity associated with many forms of orthopedic skeletal disease. Several of the more common orthopedic applications of bone scanning have been described above, while equally important topics such as prothesis loosening, avascular necrosis, and the reflex sympathetic dystrophy syndrome were not considered. Thus, for a great range of benign skeletal pathology, bone scanning can provide the orthopedic surgeon with practical information concerning the cause of the patient's pain, the true significance of otherwise questionable radiographic findings, the extent of disease and the results of orthopedic surgical treatment.

Effect of Sn(II) ion concentration and heparin on technetium-99m red blood cell labeling.

While convenience and economy favor the use of in vivo methods for labeling red blood cells (RBCs) with [99mTc]pertechnetate, previous reports suggested that patient medication such as heparin might interfere and thus result in inferior quality images. In this study, using a canine model, the role of stannous Sn(II) ion in in vivo and in vitro labeling of RBCs both in the presence and absence of a therapeutic dose of heparin was investigated. Our results showed that Sn(II) ion concentration of 20 micrograms/kg body weight levels provided better than 80% in vivo labeling efficiency enabling high quality blood-pool images even in the presence of therapeutic doses of heparin.

Evaluation of regional cerebral blood flow in massive intracerebral calcifications.

Fahr's disease is histopathologically characterized by massive bilateral calcifications of the cerebral basal ganglia, the dentate nuclei of the cerebellum and both the cerebral and cerebellar cortices. We report a case of Fahr's disease in which a 99mTc-hexamethyl-propylenamine oxime (99mTc-HMPAO) brain SPECT study was used to evaluate regional cerebral blood flow to the calcified regions. There was markedly decreased perfusion to the basal ganglia bilaterally as well as decreased perfusion to the cerebral cortices that correlated well with the patient's clinical condition.

Isolated muscular sarcoidosis causing fever of unknown origin: the value of gallium-67 imaging.

An unusual case of a patient with a long-standing fever of unknown origin (FUO) is presented whose gallium-67 (67Ga) images revealed increased activity only in the calf muscles bilaterally. Other imaging modalities also failed to show chest or other abnormal findings. Subsequent biopsy of the right gastrocnemius muscle revealed noncaseating granulomas consistent with the diagnosis of sarcoidosis. When using 67Ga to evaluate a patient with a FUO, imaging of the extremities should always be included. Also, when abnormal Ga-67 uptake is present in the extremities, sarcoidosis should be included in the differential diagnosis.

Intraosseous meningioma: appearance on bone scintigraphy over five years.

While meningiomas are common intradural tumors, such lesions only rarely arise outside of the meninges. All meningiomas, however, may slowly enlarge causing concern for malignancy. We report the appearance of an intraosseous meningioma in the patient with a history of breast carcinoma where the lesion progressively enlarged over a period of 5 yr to reach approximately three times the original size.

Iodine-131 contamination from thyroid cancer patients.

High-dose radioactive iodine therapy using 131I is the treatment of choice for patients with thyroid cancer following thyroidectomy. Because of the large amount of activity which is excreted during hospitalization, contamination hazard from 131I excretion via perspiration, saliva, breath and urine may arise. In eight patients treated with doses of 131I ranging from 3.7 to 14.8 GBq (100-400 mCi), activity levels were measured in room air, from room surfaces, the toilet, the patients' exhaled breath, skin, saliva and toothbrushes, and the gloves used by medical staff. Thyroid bioassays were also performed on medical staff personnel caring for these patients both before and two days after administration of the treatment dose. Removable activity from the skin was positively correlated with treatment dose and reached a maximum at 24 hr post-therapy. Removable activity from room surfaces exceeded the level of contamination which requires clean-up in a restricted area during the patient's hospitalization. Thyroid bioassays on medical staff showed no significant uptake 2 days after treatment. The relatively high activities present in the saliva, urine and on the skin of these patients emphasizes the need for all individuals coming in contact with these patients to be made aware of the contamination hazard present.

The use of radionuclide cisternography in the diagnosis of pleural cerebrospinal fluid fistulae.

Radionuclide cisternography (RNC) is an excellent method of studying cerebrospinal fluid (CSF) dynamics and fistulous communications. Two patients are described in which pleural cerebrospinal fluid fistulae were found by this technique. In addition, marking the area presurgically reduced operating room time in one patient. Such communications are important to locate since they can cause significant loss of CSF as well as provide a pathway for pathogens to enter the central nervous system.

Photon deficient bone metastasis of hepatocellular carcinoma with avid gallium-67 uptake.

While bone metastases producing photon deficient defects on bone scintigraphy have previously been reported, this finding has not been emphasized for hepatocellular carcinoma (HCC). Furthermore, "filling-in" of such photon deficient defects with 67Ga at skeletal sites of metastatic HCC has not been described. In this case report, the combination of a photon deficient defect on bone scintigraphy and avid accumulation of 67Ga in this same area was of value in confirming the diagnosis of metastatic HCC.

Phosphorus-32-chromic phosphate for ovarian cancer: I. Fractionated low-dose intraperitoneal treatments in conjunction with platinum analog chemotherapy.

UNLABELLED: For many years, 32P-chromic phosphate (32P-CP) intraperitoneal instillations and platinum analogue chemotherapy have been used to treat disseminated ovarian cancer. To investigate possible enhancement of 32P-CP irradiation due to the concomitant administration of chemotherapy, in vitro studies were undertaken. Based on those laboratory investigations, a clinical regimen of combined 32P-CP and platinum analogue chemotherapy was developed. METHODS: In vitro enhancement of 32P-CP cytotoxicity by cisplatin was studied in cultured human ovarian adenocarcinoma (CHOA) cell lines and in a fibroblast cell strain. In addition, ovarian cancer cells obtained from the malignant abdominal ascites and pleural effusions of 10 individual patients were also studied ex vivo. As part of routine clinical care, 30 patients with disseminated ovarian adenocarcinoma underwent up to eight monthly cycles of platinum analogue chemotherapy with concomitant intraperitoneal instillation of 5 mCi of 32P-CP at each monthly chemotherapy cycle. RESULTS: There was an enhanced and possibly supra-additive effect of cisplatin on the cytotoxicity from 32P-CP irradiation. For the 30 patients, the survival rate at 3 yr was 63%. CONCLUSION: Phosphorus-32 CP low-dose intraperitoneal treatments in conjunction with platinum analogue chemotherapy is a promising approach for the treatment of disseminated intraperitoneal ovarian cancer.

Concentration of In-111-oxine-labeled autologous leukocytes in noninfected and nonrejecting renal allografts: concise communication.

Autologous leukocytes labeled with In-111 oxine (ILL) concentrated in the renal allografts of eight patients for whom transplant rejection, infection, or acute tubular necrosis (ATN) could be excluded. All patients had good-to-adequate renal function at the time of ILL scintigraphy, and none developed rejection or renal transplant failure during a 1-mo follow-up period. It is concluded that normally functioning renal allografts without evidence of rejection, infection, or ATN often will concentrate ILL. When a baseline study is not available for comparison, this phenomenon limits the value of ILL scintigraphy as a diagnostic test for transplant rejection or infection.

Enterogastric bile reflux during technetium-99m-sestamibi cardiac imaging.

UNLABELLED: Enterogastric bile reflux (EGBR), a risk factor for both gastritis and esophagitis, is a potentially treatable noncoronary cause for chest pain. METHODS: To investigate the frequency of EGBR during different 99mTc-sestamibi cardiac imaging, 1405 consecutive 99mTc-sestamibi SPECT myocardial perfusion studies were reviewed. RESULTS: One hundred sixteen of the 1405 patient studies (8.3%) showed EGBR with roughly equal numbers of patients having marked (43 patients), moderate (38 patients) or minimal (35 patients) intensity of abnormal gastric activity. Two examinations showed gastroesophageal reflux of activity. EGBR was less frequent with treadmill stress testing (5.5% patients) than with pharmacologic stress testing using either dipyridamole (11% of patients) or dobutamine (9.2% of patients) (p > 0.005). EGBR also was more frequent in patients over 40 yr of age. Finally, the prevalence of upper gastrointestinal symptoms and the frequency of established upper gastrointestinal diagnoses correlated strongly with the presence and intensity of EGBR. CONCLUSION: Clarification of the full clinical significance of EGBR during 99mTc-sestamibi cardiac imaging is a topic for future research. Nonetheless, the imaging finding of EGBR may, in fact, identify a potentially treatable noncoronary cause for chest pain.

Right aortic arch: demonstration by first-pass and multigated radionuclide ventriculography.

Right aortic arch is a rare congenital anomaly associated with abnormal development of the paired embryological aortic arches. While various abnormalities of the great vessels have been described using both first-pass and multigated radionuclide ventriculographic studies, diagnosis of a right-sided aortic arch has typically required a radiographic contrast technique. We present a case of a patient with a suspected right-sided aortic arch diagnosed by radionuclide methods.

Comparison of technetium-99m pyrophosphate and technetium-99m DTPA aerosols for SPECT ventilation lung imaging.

Although [99mTc] diethylenetriaminepentaacetic acid (DTPA) is currently the most widely used radioaerosol, rapid alveolar clearance limits its usefulness for single photon emission computed tomography (SPECT) ventilation lung imaging. Previous research has shown that [99mTc]phosphate compounds have high alveolar deposition and slow clearance and thus provide suitable aerosols for pulmonary ventilation studies. We have compared the pulmonary retention and blood levels of [99mTc]pyrophosphate (PYP) and [99mTc]DTPA in eight normal nonsmoking male volunteers. These two radioaerosols have comparable pulmonary deposition. Technetium-99m PYP, however, has a much slower pulmonary clearance which allows sufficient time (20 or more minutes) for SPECT data acquisition using a single-headed rotating gamma camera. While the radiation absorbed dose to the lungs for [99mTc]PYP (0.31 rad/mCi) is greater than for [99mTc]DTPA (0.11 rad/mCi), it is at a clinically acceptable and safe level.

Early diagnosis of acute postoperative renal transplant rejection by indium-111-labeled platelet scintigraphy.

A prospective evaluation of 111In-labeled platelet scintigraphy (IPS) for the early diagnosis of acute postoperative renal transplant rejection (TR) was undertaken. The results of IPS were compared with in vitro biochemical tests, the clinical finding of graft tenderness, and combined [99mTc]DTPA and [131I]orthoiodohippurate scintigraphy. With a sensitivity of 0.93 and a specificity of 0.95, IPS provided otherwise unavailable diagnostic information. Furthermore, postoperative IPS was a good predictor of long-term allograft survival.

Comparison of high-resolution MRI and SPECT bone scintigraphy for noninvasive imaging of the temporomandibular joint.

Prospective evaluation by magnetic resonance imaging (MRI) and both single photon emission computed tomography (SPECT) and planar bone scintigraphy was undertaken in 31 temporomandibular joints (TMJs) of 21 symptomatic patients. When compared with the results of subsequent arthrography, MRI (0.88) was more sensitive than SPECT (0.76) or planar (0.56) scintigraphy for detection of internal derangement of the TMJ. A diagnostic sensitivity of 0.96 was achieved when the results of either MRI or SPECT was considered evidence of internal joint derangement. Five symptomatic TMJs, clinically thought to be abnormal, were positive on SPECT but showed no evidence of anterior disk displacement at the time of arthrography. In such instances, SPECT may be detecting functionally significant altered joint mechanics that are not evident on anatomic imaging of the TMJ.