Rapid imaging of infections with a monoclonal antibody fragment (LeukoScan).

The diagnostic accuracy for imaging infection with a technetium-99m-labeled antigranulocyte Fab' fragment (LeukoScan) was prospectively examined in a multicenter study. Scintigraphy was performed in 53 patients at 1 to 6 hours and at 24 hours after injection of the labeled antibody fragment. Thirty-nine sites of infection were detected and confirmed by histologic study, cytologic study, other imaging procedures, or by followup. Thirty-eight of the 53 patients also were studied with technetium-99m-Exametazim or indium-111-oxine labeled leukocytes within 1 week of the LeukoScan study. In 21 patients with 25 osteomyelitic lesions, LeukoScan recognized 13 of the lesions as being true positive ones, 10 as being true negative ones, and 2 as being false negative ones, whereas the leukocyte scan showed 9 true positive results, 5 true negative results, and 2 false negative ones. Sensitivity specificity, and diagnostic accuracy of LeukoScan were 90.0 %, 84.6 %, and 87.9 %; and with autologous leukocyte scintigraphy were 83.9%, 76.5%, and 81.3%, respectively. The sensitivity of LeukoScan was independent of the amount of the labeled antibody injected (0.1 - < 0.5 mg, 96.2%; 0.5 - < 0.9 mg, 80.0%; 0.9 - 1.0 mg, 77.8%). False positive lesions were detected in a periprosthetic calcification, a frontal hyperostosis, and 2 periprosthetic hips that had loosened. Human antimouse antibody could not be detected in any of the 13 patients tested 1 or 3 months after injection. LeukoScan is suitable for imaging infectious lesions and may have diagnostic advantages compared with autologous leukocyte scintigraphy.

Absorbed radiation dose to humans from technetium-99m-teboroxime.

Tissue distribution data obtained in nine normal volunteers were used to estimate the radiation dose to humans after intravenous administration of 99mTc-teboroxime (Cardiotec). Organ uptake as percent of injected dose was measured using quantitative SPECT. Non-linear regression analysis was performed on the organ time-activity data using SYSTAT software. Cumulative activities in these organs were determined by calculating the area under the respective curves after accounting for the physical decay of the radionuclide. The absorbed dose to individual organs was estimated using the MIRDOSE 2 program. The gallbladder and the upper large intestine (ULI) are the target organs and will receive respectively 26.5 and 33.2 muGy/MBq (98 and 123 mrad/mCi) 99mTc-teboroxime under the assumption that the gallbladder empties every 6 hr. The dose to the gallbladder decreases at shorter emptying intervals; with intervals of 3, 4, and 5 hr, the respective doses to the gallbladder are 18.2, 21.0 and 23.7 muGy/MBq (67.4, 77.8, and 87.9 mrad/mCi) 99mTc-teboroxime. However, the dose to ULI remains almost constant at 123 mrad/mCi and will be the limiting factor.

A neutral lipophilic technetium-99m complex for regional cerebral blood flow imaging.

Technetium-99m-DMG-2MP (Chloro[bis[2,3-butanedionedioxime(1-)-0][2,3- butanedionedioximato (2-)-N,N',N'',N''',N'''',N'''''] (2-methylpropyl borato (2-))technetium]), also known as SQ 32097 is a member of a family of neutral lipophilic compounds generally known as boronic acid adducts of technetium dioxime complexes (BATOs). After i.v. administration, the concentration of [99mTc]DMG-2MP in various regions of the brain appears to be proportional to blood flow. In rats, 1.1% ID was in the brain at 5 min postinjection when the blood contained less than 3% ID. Over 24 hr excretion was 59% in the feces and 23% in the urine. The activity in monkey brain at 5 min was 2.8% ID and it cleared with a t1/2 of 86 min. Autoradiographs of monkey brain sections showed excellent regional detail with a gray/white ratio of 3.6 at 10 min. The distribution of [99mTc]DMG-2MP in the monkey brain corresponds to the known cytoarchitectural pattern of cerebral glucose metabolism. The properties of [99mTc]DMG-2MP make it a potentially useful agent for cerebral perfusion imaging in man.

A neutral technetium-99m complex for myocardial imaging.

Technetium-99m-CDO-MeB [Bis[1,2-cyclohexanedione-dioximato(1-)- O]-[1,2-cyclohexanedione dioximato(2-)-O]methyl-borato(2-)- N,N',N'',N''',N'''',N''''')-chlorotechnetium) belongs to a family of compounds generally known as boronic acid adducts of technetium dioxime complexes (BATOs). It has an intrinsic affinity for the myocardium, with negligible lung activity and rapid blood clearance. The uptake of 3.44% ID in rat heart at 1 min postinjection for [99mTc]CDO-MeB versus 3.03% for 201TI indicates high extraction of [99mTc]CDO-MeB by the myocardium. In dogs an ischemic defect is clearly seen in SPECT images obtained 10 min after injection of [99mTc]CDO-MeB. Tissue distribution data in rats show that [99mTc]CDO-MeB is excreted primarily in the feces and to a lesser extent in the urine. Approximately 80% of the activity is excreted within 24 hr after injection.

N,N'-bis(S-benzoylmercaptoacetamido) ethylenediamine and propylenediamine ligands as renal function imaging agents. I. Alternate synthetic methods.

A new method was developed to synthesize tetradentate ligands containing the N,N'-bis(S- benzoylmercaptoacetyl ) ethylenediamine and propylenediamine moieties (DADS compounds). Methods are also represented with which to synthesize some of the positional isomers of the above compounds. These isomers represent a new class of compounds. A total of 21 different compounds were prepared. These will be used in an effort to establish a relationship between structure and renal imaging properties.

New diphosphonate compounds for skeletal imaging: comparison with methylene diphosphonate.

Three-hour biodistribution of Tc-99m complexes of six diphosphonates was compared in rabbits with tibial lesions to determine which was best for detection of focal bone lesions. Sr-85 was used as a standard. N,N-dimethylaminomethylene diphosphonate (DMAD) was the only agent with a higher lesion/normal bone ratio than methylene diphosphonate (MDP), attributable to lower concentration in normal bone. Hydroxymethane diphosphonate (HDP) and 2,3-dicarboxypropane-1, 1-diphosphonate (DPD) demonstrated higher concentration than MDP in normal bone without improving lesion contrast. They also exhibited much higher uptake in the liver and kidney, as well as muscle and red marrow in the case of DPD. None was superior to MDP as an all-purpose skeletal agent, though others may be better for specific applications.

Detection of experimentally produced acute pulmonary arterial occlusion by methyl iodide-131 inhalation imaging.

Methyl iodide-131 (CH3I-131) is described as an agent for detection of acute experimentally produced pulmonary arterial occlusion in dogs. When gaseous CH3I-131 is inhaled, radioactivity passes instantaneously from the alveoli to the lung capillary bed. Where pulmonary blood flow exists, activity is washed out into the systemic circulation, but in areas of blood stasis, a transient pulmonary "hot spot" remains. CH3I-131 is easily produced and inexpensive, but administration is awkward and strict radiation safety precautions are mandatory.