(18)F-fluorodeoxyglucose positron-emission tomography-computed tomography to diagnose recurrent cancer.

BACKGROUND: Sometimes the diagnosis of recurrent cancer in patients with a previous malignancy can be challenging. This prospective cohort study assessed the clinical utility of (18)F-fluorodeoxyglucose positron-emission tomography-computed tomography ((18)F-FDG PET-CT) in the diagnosis of clinically suspected recurrence of cancer. METHODS: Patients were eligible if cancer recurrence (non-small-cell lung (NSCL), breast, head and neck, ovarian, oesophageal, Hodgkin's or non-Hodgkin's lymphoma) was suspected clinically, and if conventional imaging was non-diagnostic. Clinicians were asked to indicate their management plan before and after (18)F-FDG PET-CT scanning. The primary outcome was change in planned management after (18)F-FDG PET-CT. RESULTS: Between April 2009 and June 2011, 101 patients (age, median 65 years; 55% female) were enroled from four cancer centres in Ontario, Canada. Distribution by primary tumour type was: NSCL (55%), breast (19%), ovarian (10%), oesophageal (6%), lymphoma (6%), and head and neck (4%). Of the 99 subjects who underwent (18)F-FDG PET-CT, planned management changed after (18)F-FDG PET-CT in 52 subjects (53%, 95% confidence interval (CI), 42-63%); a major change in plan from no treatment to treatment was observed in 38 subjects (38%, 95% CI, 29-49%), and was typically associated with (18)F-FDG PET-CT findings that were positive for recurrent cancer (37 subjects). After 3 months, the stated post-(18)F-FDG PET-CT management plan was actually completed in 88 subjects (89%, 95% CI, 81-94%). CONCLUSION: In patients with suspected cancer recurrence and conventional imaging that is non-diagnostic, (18)F-FDG PET-CT often provides new information that leads to important changes in patient management.

Vertebral fracture prevalence in a referral population of 750 Canadian men and women.

AIM: To establish the prevalence of vertebral fracture (VF) in a representative sample of 750 Canadians and to examine the relationships between VF prevalence and bone mineral density (BMD) at the spine and proximal femur. MATERIALS AND METHODS: X-ray-based dual-photon absorptiometry (DXA) was used to perform measurements of lumbar spine BMD, proximal femur BMD, and VF assessment (VFA). RESULTS: Two hundred and fifty-nine VFs were identified in 156 patients and the prevalence of unknown or unsuspected VF was 18.7%. For premenopausal women and for men, there was no difference in BMD at either the spine or the hip whether or not there was at least one VF. For postmenopausal women, BMD of the total region of the proximal femur was statistically lower (p < 0.001) in women with at least one VF whereas spine BMD only tended to be less (0.10 > p > 0.05). Proximal femur BMD was lower for postmenopausal women with more VF, while spine BMD was virtually unchanged as the number of VF increased. Neither spine nor hip BMD was lower for men with more VF. A strong association was observed in postmenopausal women between an age-dependent increase in VF prevalence and a reduction in femoral BMD. Such an association was not present in men. CONCLUSION: VFs are common, are often independent of either spine or hip BMD, and frequently go unnoticed. Therefore, VFA should be part of a routine assessment of fracture risk.

Radionuclide therapy in neuroendocrine tumours: a systematic review.

The purpose of this systematic review was to investigate the effects of therapeutic radiopharmaceuticals in patients with different types of advanced neuroendocrine tumour (NETs). A literature search was carried out in MEDLINE and EMBASE from January 1998 to November 2010. The Cochrane Library (to Issue 10, 2010) and the Standards and Guidelines Evidence Inventory of Cancer Guidelines, including over 1100 English-language cancer guidelines from January 2003 to June 2010, were also checked. No existing systematic reviews or clinical practice guidelines based on a systematic review or randomised controlled trials focusing on this topic were found. Twenty-four fully published articles were abstracted and summarised: 16 articles focused on five peptide receptor radionuclide therapy ((111)In-DTPAOC, (90)Y-DOTALAN, (90)Y-DOTATOC, (90)Y-DOTATATE, and (177)Lu-DOTATATE) and eight focused on (131)I-MIBG treatment. Limited evidence from a historical comparison of studies in one centre supported that (177)Lu-DOTATATE might be associated with greater clinical outcomes compared with (90)Y-DOTATOC or (111)In-DTPAOC. The severe toxicities for (177)Lu-DOTATATE included hepatic insufficiency in 0.6%, myelodysplastic syndrome in 0.8% and renal insufficiency in 0.4% of patients in this study. Insufficient evidence suggested efficacy of (131)I-MIBG in adult NET patients, but the overall tumour response rate from (131)I-MIBG was 27-75% for malignant neuroblastoma, paraganglioma or pheochromocytoma. Haematological toxicities were the main severe side-effects after (131)I-MIBG and 4% of patients developed secondary malignancies in one study. To date, peptide receptor radionuclide therapy seems to be an acceptable option and is relatively safe in adult advanced NET patients with receptor uptake positive on scintigraphy, but patients' renal function must be monitored. (131)I-MIBG may be effective for malignant neuroblastoma, paraganglioma or pheochromocytoma, but its side-effects need to be considered. No strong evidence exists to support that one therapeutic radiopharmaceutical is more effective than others. Well-designed and good-quality randomised controlled trials are required on this research topic.

CCS/CAR/CANM/CNCS/CanSCMR joint position statement on advanced noninvasive cardiac imaging using positron emission tomography, magnetic resonance imaging and multidetector computed tomographic angiography in the diagnosis and evaluation of ischemic heart disease--executive summary.

BACKGROUND: Over the past few decades, advanced imaging modalities with excellent diagnostic capabilities have emerged. The aim of the present position statement was to systematically review existing literature to define Canadian recommendations for their clinical use. METHODS: A systematic literature review to 2005 was conducted for positron emission tomography (PET), multidetector computed tomographic angiography and magnetic resonance imaging (MRI) in ischemic heart disease. Papers that met the criteria were reviewed for accuracy, prognosis data and study quality. Recommendations were presented to primary and secondary panels of experts, and consensus was achieved. RESULTS: Indications for PET include detection of coronary artery disease (CAD) with perfusion imaging, and defining viability using fluorodeoxyglucose to determine left ventricular function recovery and/or prognosis after revascularization (class I). Detection of CAD in patients, vessel segments and grafts using computed tomographic angiography was considered class IIa at the time of the literature review. Dobutamine MRI is class I for CAD detection and, along with late gadolinium enhancement MRI, class I for viability detection to predict left ventricular function recovery. Imaging must be performed at institutions and interpreted by physicians with adequate experience and training. CONCLUSIONS: Cardiac imaging using advanced modalities (PET, multidetector computed tomographic angiography and MRI) is useful for CAD detection, viability definition and, in some cases, prognosis. These modalities complement the more widespread single photon emission computed tomography and echocardiography. Given the rapid evolution of technology, initial guidelines for clinical use will require regular updates. Evaluation of their integration in clinical practice should be ongoing; optimal use will require proper training. A joint effort among specialties is recommended to achieve these goals.

Treating the right patient at the right time: access to cardiovascular nuclear imaging.

Cardiovascular nuclear medicine uses agents labelled with radioisotopes that can be imaged with cameras (single-photon emission tomography [SPECT] or positron emission tomography [PET]) capable of detecting gamma photons to show physiological parameters such as myocardial perfusion, myocardial viability or ventricular function. There is a growing body of literature providing guidelines for the appropriate use of these techniques, but there are little data regarding the appropriate timeframe during which the procedures should be accessed. An expert working group composed of cardiologists and nuclear medicine specialists conducted an Internet search to identify current wait times and recommendations for wait times for a number of cardiac diagnostic tools and procedures, including cardiac catheterization and angioplasty, bypass grafting and vascular surgery. These data were used to estimate appropriate wait times for cardiovascular nuclear medicine procedures. The estimated times were compared with current wait times in each province. Wait time benchmarks were developed for the following: myocardial perfusion with either exercise or pharmacological stress and SPECT or PET imaging; myocardial viability assessment with either fluorodeoxyglucose SPECT or PET imaging, or thallium-201 SPECT imaging; and radionuclide angiography. Emergent, urgent and nonurgent indications were defined for each clinical examination. In each case, appropriate wait time benchmarks were defined as within 24 h for emergent indications, within three days for urgent indications and within 14 days for nonurgent indications. Substantial variability was noted from province to province with respect to access for these procedures. For myocardial perfusion imaging, mean emergent/urgent wait times varied from four to 24 days, and mean nonurgent wait times varied from 15 to 158 days. Only Ontario provided limited access to viability assessment, with fluorodeoxyglucose available in one centre. Mean emergent/urgent wait times for access to viability assessment with thallium-201 SPECT imaging varied from three to eight days, with the exception of Newfoundland, where an emergent/urgent assessment was not available; mean nonurgent wait times varied from seven to 85 days. Finally, for radionuclide angiography, mean emergent/urgent wait times varied from two to 20 days, and nonurgent wait times varied from eight to 36 days. Again, Newfoundland centres were unable to provide emergent/urgent access. The publication of these data and proposed wait times as national targets is a step toward the validation of these recommendations through consultation with clinicians caring for cardiac patients across Canada.

Cardiac risk stratification using dipyridamole myocardial perfusion imaging and ambulatory ECG monitoring prior to vascular surgery.

Both dipyridamole myocardial perfusion imaging (cardiolite) and ambulatory ECG monitoring (Holter) for silent ischaemia have been found to be useful for stratification of cardiac risk in patients undergoing vascular surgery. The purpose of this study was to compare the diagnostic accuracy of these two non-invasive tests for prediction of perioperative cardiac events. One hundred patients (86 males, 14 females; mean age 67 +/- 8 years) underwent out-patient 48 h Holter monitoring and cardiolite imaging prior to vascular surgery (70 abdominal aortic aneurysm, 21 aortobifemoral, nine femoralpopliteal grafts). Ischaemia on Holter was defined as one or more episodes of ST segment depression 1 mm or greater, lasting 1 min or longer. Myocardial perfusion imaging was carried out with the high dose dipyridamole protocol (0.84 mg/kg), cardiolite and planar imaging. Ischaemia was defined as a segmental perfusion abnormality following dipyridamole with improved perfusion on rest imaging. Holter was positive for ischaemia in 34/100 patients (34%). Cardiolite scans were positive for ischaemia in 30/100 patients (30%). Perioperative myocardial infarction occurred in nine patients (two cardiac deaths). [table: see text] The diagnostic accuracy of the two tests was similar, with a low positive predictive value of 15-20%, and an extremely high negative predictive value of 94-96%. The event rate in patients with both tests negative was 2/48 (4.2%), with only one test positive 3/40 (7.5%) and with both tests positive 4/12 (33%). A reasonable approach to risk stratification would be to obtain either a Holter or cardiolite scan initially.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral perfusion imaging with technetium-99m HMPAO following cerebral trauma. Initial experience.

Thirteen patients with cerebral trauma were studied for cerebral perfusion by the use of Tc-99m HMPAO scanning. CT imaging was performed on nine patients. Because of their clinical condition, four patients were scanned only in the planar mode to help establish the diagnosis of brain death. Other indications for study included gunshot wound and blunt or sharp object trauma with or without skull fracture. In all cases, HMPAO scans showed defects with a quality equivalent to or greater than that demonstrated by CT. Our initial results suggest that HMPAO may predict the degree of permanent damage and which patients may develop post-traumatic headache. A diagnosis of brain death can be established without the withdrawal of medical therapy.

Comparison of left ventricular function and myocardial perfusion for evaluating perioperative cardiac risk of abdominal aortic surgery.

The measurement of left ventricular function by gated blood pool scanning and of myocardial perfusion by dipyridamole thallium imaging were compared in a prospective study of patients who had abdominal aortic aneurysm or aortoiliac occlusive disease to determine which measurement was the better predictor of postoperative cardiac complications. Sixty-six men and 19 women (mean age 67 years) underwent both tests before admission for surgery. Fifty-six had repair of an abdominal aortic aneurysm, and 29 had reconstruction for aortoiliac occlusive disease. In 17 patients the left ventricular ejection fraction was less than 50%. Dipyridamole thallium imaging was positive, showing redistribution, in 45 patients. Postoperative cardiac complications occurred in 33 patients. The sensitivity of dipyridamole thallium imaging (91%) was significantly (p less than 0.01) greater than that observed with gated blood pool scanning (27%). However, the specificity of gated blood pool scanning (85%) was similar to that of dipyridamole thallium imaging (71%). Diagnostic accuracy was greatest with dipyridamole thallium imaging (79% versus 62% [p less than 0.02]). Dipyridamole thallium imaging is superior to gated blood pool scanning for perioperative evaluation of vascular surgical patients.

A kit for labelling erythrocytes or leukocytes with technetium-99m.

A pretinning method for labelling erythrocytes with technetium-99m (99mTc) in vitro has been developed using a kit which contains stannous chloride stabilized with gentisic acid. Labelling efficiency was 97.3% (SD 1.4%) for 80 patients. The method requires less time than the Brookhaven kit and results in a smaller volume for reinjection but provides equivalent clinical results. We have previously shown that leukocytes labelled with 99mTc using the same gentisic acid kit are clinically equivalent to those labelled with HMPAO; thus, the kit is versatile and cost-effective.

Radiopharmaceutical factors in the variable quality of [99mTc]HM-PAO images of the brain.

Variability in the quality of [99mTc]HM-PAO images of the brain has been attributed to differences between kits and the addition of excessive amounts of pertechnetate to the kits. A retrospective study showed no significant differences between batches of kits with respect to radiochemical purity (RCP) or image quality. Up to 3000 MBq (81 mCi) pertechnetate could be added to the kit without adversely affecting RCP or image quality. It was shown that image quality was directly affected by RCP at time of injection and dropped sharply when RCP fell below 85%. Interstitial injection and mixing with blood prior to injection also resulted in poor image quality. Pretreatment with perchlorate reduced uptake of activity in the parotid glands; this improved image quality and reduced the influence of RCP.

In vitro comparison of HMPAO and gentisic acid for labelling leukocytes with 99mTc.

Leukocytes can be labelled with 99mTc using HMPAO and gentisic acid methods. We compared the two methods with respect to labelling efficiency on mixed leukocytes and isolated polymorphonuclear (PMN) and mononuclear (MN) cells, and the in vitro stability of the label. HMPAO produced approximately 70% labelling efficiency on mixed or PMN cells and the label was stable in saline or plasma. Labelling efficiency on MN was only 14% and was less stable. Gentisic acid produced a labelling efficiency of 52% on PMN and 35% on MN; both were stable in saline but less stable in plasma. In conclusion, HMPAO produces higher labelling efficiency and the label shows greater in vitro stability in plasma. However, gentisic acid is much less expensive to use, allows labelling of MN cells, and should result in more favourable microdosimetry. Preliminary clinical results suggest that gentisic acid is equivalent to HMPAO but has the advantage of being much cheaper.

Clinical use of technetium-99m HM-PAO for determination of brain death.

We report our clinical experience with the use of [99mTc]hexamethyl propyleneamine oxime (HM-PAO) in establishing a diagnosis of brain death in 11 patients following trauma to the head and four patients who suffered atraumatic injuries. In 9/15 studies there was no intracranial flow present and brain death was then confirmed by standard criteria. Of the remaining 6/15 studies which showed evidence of cerebral perfusion, 3/6 patients underwent a subsequent HM-PAO study which showed cessation of perfusion. One additional patient died of pneumonia and two patients survived. Thus, in all cases where there was no flow present the diagnosis of brain death was later confirmed whereas three patients clinically thought to be brain dead showed significant perfusion and survived the cerebral trauma. HM-PAO may be useful in determination of brain death because it provides unequivocal results, can be performed by planar imaging at the bedside, and does not require withdrawal of medical therapy, thus allowing a diagnosis to be established more rapidly.

Technetium-99m spiperone dithiocarbamate: a potential radiopharmaceutical for dopamine receptor imaging with SPECT.

Spiperone dithiocarbamate (SPDC) was prepared by reacting spiperone with carbon disulfide followed by sodium hydroxide. SPDC was labelled with 99mTc by reduction of pertechnetate with formamidine sulfinic acid or sodium dithionite at alkaline pH, resulting in approximately 40% incorporation of 99mTc. The lipophilic complex was conveniently isolated at high specific activity and high radiochemical purity by extraction into dichloromethane, which was then evaporated and the residue was redissolved in a 1:3 mixture of ethanol and saline containing 0.1 mg/mL gentisic acid. Biodistribution studies following i.p. injection in rats showed low uptake of radioactivity in the brain, but striatum/cortex and striatum/cerebellum ratios were reduced by pretreatment with haloperidol. This agent may allow imaging of dopamine D-2 receptors using single-photon emission computed tomography (SPECT).

Routine determination of radiochemical purity of 99mTc-MIBI.

The manufacturer recommends that the radiochemical purity of 99mTc-MIBI be determined with alumina TLC plates developed in ethanol, but for routine use this is slow and requires care. After comparing a variety of systems, we obtained equivalent results using ITLC-SG strips developed with saline to determine [99mTc]pertechnetate and with acetone to determine 99mTc colloid; % 99mTc-MIBI was determined by difference from 100%. These separations are the opposite of those obtained with the routine polar 99mTc radiopharmaceuticals. Equivalent results were obtained even more rapidly by extracting 99mTc-MIBI from water into chloroform.

Technetium-99m dithiocarbamates as potential brain agents: evaluation of aliphatic and amine-containing analogues.

Technetium-99m forms a lipophilic complex with diethyldithiocarbamate (DDC) but this complex is not retained in the brain as is thallium-201 DDC. We therefore prepared a series of aliphatic and amine-containing analogues of DDC and evaluated the properties of their 99mTc complexes in vitro and in vivo. The ethyl acetate/buffer partition coefficients of the amine-containing derivatives showed a response to pH. Four of the five complexes were less stable than DDC in vitro and showed greater retention in rabbit brain. These agents warrant further investigation for cerebral perfusion imaging with SPECT.

Technetium-99m HM-PAO stereoisomers: differences in interaction with glutathione.

[99mTc]HM-PAO exists as two stereoisomers, d,1 and meso, only one of which is retained in the brain. It has been suggested recently that the biodistribution of [99mTc]d,1-HM-PAO can be explained by its interaction with glutathione (GSH) in the tissues. We studied the interactions of the d,1 and meso isomers with GSH in vitro by measuring the partitioning of activity between ethyl acetate and aqueous GSH solutions at various concentrations. Partitioning of both isomers demonstrated a sigmoidal relationship with GSH concentration, but the d,1 isomer showed eightfold greater reactivity than the meso isomer. In a separate experiment, the d,1 isomer showed a sevenfold greater interaction rate with GSH than the meso isomer. These results suggest that the stereoisomers of [99mTC]HM-PAO show differences in their interaction rate with GSH which may explain their different retention in the brain.