99mTc-citrate versus 67Ga-citrate for the scintigraphic visualization of inflammatory lesions

Citric acid was labeled with 99mTc with an efficiency of > 99%. The biodistribution of 99mTc-citrate was studied in mice with turpentine-induced abscesses in comparison to 67Ga-citrate. The max. abscess/muscle concentration ratios were 4.61 +/- 1.92 (3 h) for 99mTc-citrate and 4.76 +/- 2.04 (4 h) for 67Ga-citrate. Arthritis was induced in 10 rabbits by intra-articular injection of ovalbumin Scintigrams obtained 4 days later and at 3 h post-injection of 99mTc-citrate showed increased activity involving the synovium. The max. arthritic/contralateral knee ratio was 3.19 +/- 1.29 (3 h) and 6.47 +/- 3.71 (24 h) for 99mTc- and 67Ga-citrate, respectively. The blood clearance curve of 99mTc-citrate in rabbits was biexponential with a fast (T1/2 = 36 min) and a slow (T1/2 = 18 h) component, compared to mono-exponential clearance of 67Ga-citrate (T1/2 = 23 h). In 10 patients with rheumatoid arthritis whole-body scintigrams and spot images of involved joints indicated localization of the tracer in inflamed tissues. The mean target-to-soft tissue ratios were 3.04 +/- 0.81 and 4.95 +/- 2.56 for 99mTc-citrate and 99mTc-MDP, respectively. Renal clearance of radioactivity was evident from the scintigrams. Our results demonstrated that 99mTc-citrate is effective as a radiopharmaceutical for the visualization of inflammatory lesions and may be preferred to 67Ga-citrate due to the ideal physical characteristics of the radionuclide, easy preparation, low cost, early accumulation and the preference for the renal route of excretion.     

Reading epilepsy: report of five new cases and further considerations on the pathophysiology

Liposomes, microscopic lipid vesicles consisting of concentric phospholipid bilayers enclosing discrete aqueous spaces, have been investigated extensively as carries for drugs in attempts to achieve selective deposition and/or reduced toxicity. Liposomes radiolabeled with gamma emitters (67Ga, 111In and 99mTc) have been used for imaging purposes. Liposomes as formulated in the past, are rapidly taken up by cells of the mononuclear phagocyte system, primarily those located in liver and spleen. However, it has been shown during the last two decades that the in vivo behavior of liposomes can be modulated by modifying their formulation. The size and the lipid composition have a major influence on the blood clearance rate, hepatic uptake and splenic uptake of liposomes. The development of long circulating liposomes, in particular coating of the bilayer with polyethyleneglycol (PEG) resulted in liposomes that oppose recognition by the MPS, thus displaying even longer circulatory half-lives. By carefully adjusting the liposomal formulation, the in vivo characteristics of liposomes can be tailored such that they become suitable vehicles for imaging various pathological processes in vivo. Liposomes have been proposed for tumor imaging, for infection imaging and as blood pool markers. Here, the factors that determine the in vivo behavior of liposomes and the current status of liposome-based radiopharmaceuticals are reviewed.     

Reduction of hippocampal-kindled seizure activity in rats by stereotactic radiosurgery

The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5')-tetraphosphate) and its analogue 99mTc AppCHClppA for imaging experimental atherosclerotic lesions in New Zealand White rabbits. Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides. After acquiring the final images, the animals were sacrificed, ex vivo images of the aortas were recorded, and biodistribution was measured. 99mTc-Ap4A and 99mTc AppCHClppA accumulated rapidly in atherosclerotic abdominal aorta, and lesions were clearly visible within 30 min after injection in all animals that were studied. Both radiopharmaceuticals were retained in the lesions for 3 hr, and the peak lesion to normal vessel ratio was 7.4 to 1. Neither of the purine analogs showed significant accumulation in the abdominal aorta of normal (control) rabbits. The excised aortas showed lesion patterns that were highly correlated with the in vivo and ex vivo imaging results. The present study demonstrates that purine receptors are up-regulated in experimental atherosclerotic lesions and 99mTc-labeled purine analogs have potential for rapid noninvasive detection of plaque formation.     

Labelled Stealth liposomes in experimental infection: an alternative to leukocyte scintigraphy?

Indium-111 (111In) and technetium-99m (99Tcm) Stealth liposomes were compared with 111In- and 99Tcm-labelled white blood cells (WBC) in experimental infection in a rabbit model. Preformed polyethylene glycol-coated liposomes and separated WBC were radiolabelled with either 111In-oxine or 99Tcm-hexamethylpropyleneamine oxime (99TcM-HMPAO). After the intravenous administration of one of the four radiopharmaceuticals to rabbits with focal Staphylococcus aureus infection, scintigraphic images were recorded at various time points post-injection and the biodistribution of the radiopharmaceuticals was determined. At 4 h post-injection, uptake of 111In-WBC in the abscess was significantly higher than that of the three other products. AT later time points, 111In-WBC, 111In-liposome and 99Tcm-liposome uptake in the abscess were similar. In contrast, a 20 h post-injection, uptake of 99Tcm-WBC was significantly lower. The abscess-to-background ratios showed a similar pattern to the absolute abscess uptake: initial high values for 111In-WBC, a more gradual increase over time of the liposome preparations to the level of 111In-WBC and persistently low values for 99Tcm-WBC. Clearance from the blood of both labelled WBC preparations was significantly faster and splenic uptake significantly higher compared with those of the labelled liposomes. In conclusion, given the similar in vivo characteristics of labelled liposomes and labelled WBC, labelled liposomes may be an attractive replacement for labelled WBC, providing a continuously available, high-quality, 99Tcm-labelled radiopharmaceutical that can be prepared easily without any need to handle blood.     

Technetium-99m-antiepidermal growth factor-receptor antibody in patients with tumors of epithelial origin: part II. Pharmacokinetics and clearances

Radiolabeled antitumor antibodies hold promise for diagnostic imaging and therapy in oncology. The purpose of this study was to investigate the pharmacokinetics, clearances and possible differences of two dosage administrations of the 99mTc-labeled antiepidermal growth factor (EGF)-receptor antibody and to predict the best dose and schedule for future clinical evaluations of this radiopharmaceutical. METHODS: Nine patients (4 women, 5 men; mean age 46.4 +/- 14.0 yr) were administered 1-3 mg 99mTc-labeled anti-EGF-receptor antibody (a murine IgG2a isotype) by intravenous bolus infusion. After administration, blood samples were collected from 7 patients from an antecubital vein opposite to the injection side at intervals from 2 min to 24 hr after injection, and plasma samples were obtained for pharmacokinetic analysis. Appropriate plasma samples were examined for isotope clearance (i.e., microCi/ml at various intervals) and 99mTc complexation to plasma proteins by fast protein liquid chromatography (FPLC) analysis. Urine was collected from each patient at 3 hr intervals up to 24 hr after monoclonal antibody administration to monitor 99mTc clearance. Plasma time-activity curves were fitted to a two-compartment model using nonlinear least-squares regression analysis by the method of flexible polyhedrals. RESULTS: Plasma disappearance curves of 99mTc-labeled anti-EGF-receptor antibody were best fit by biexponential equation with a distribution half-life (t(1/2alpha)) of 0.137 +/- 0.076 hr (n = 7) and elimination half-life (t(1/2beta)) of 20.3 +/- 8.0 hr. Analysis of urine showed that activity clearance by this route amounted to 4.9% +/- 0.6% of the injected dose in 24 hr, and FPLC analysis showed no evidence of decomposition, only 6%-7% of 99mTc was in a low molecular weight species. CONCLUSION: Plasma pharmacokinetics and urine clearance indicate comparability in both doses. The pharmacokinetic properties of the 99mTc-labeled anti-EGF-receptor antibody were found to be dose-independent. These findings provide an initial characterization of the radiopharmaceutical disposition in patients and may be used as the basis for calculating a better estimate of biodistribution and dosimetry for patients who will receive 188Re-labeled anti-EGF-receptor antibody (MAb ior egf/r3) injection for radioimmunotherapy and warrants further controlled clinical trials to define the efficacy of the radiopharmaceutical.     

Excretion of endogenous and exogenous purine derivatives in sheep: effect of increased concentrate intake

The scintigraphic measurement of colonic transit is currently performed using 111In ion exchange resin pellets delivered to the colon in a capsule coated with a pH sensitive polymer, methacrylate, which dissolves in the distal ileum. However, in the USA, this requires an investigational drug permit. Our aim was to evaluate the in vitro binding characteristics of activated charcoal in milieus that mimicked gastric and small intestinal content. The in vitro incubation of activated charcoal was performed with Na99Tc(m)O4, 99Tc(m)-DTPA, 111InCl3, 111In-DTPA, 201TlCl and 67Ga-citrate in the pH range 2-4 and pH 7.2 at 37 degrees C. We estimated the association of radiopharmaceuticals with the activated charcoal over a 3 h in vitro incubation. With the exception of 67Ga-citrate, the association of activated charcoal with the other radiopharmaceuticals was approximately 100% throughout the 3 h incubation. In conclusion, activated charcoal appears to adsorb avidly with common radioisotopes, and appears promising as an alternative to resin ion exchange pellets used for the measurement of gastrointestinal transit by scintigraphy.     

Major histocompatibility complex class II antigen expression in rejecting cardiac allografts: detection using in vivo imaging with radiolabeled monoclonal antibody

BACKGROUND: Increased expression of major histocompatibility complex class II (MHC-II) antigen occurs during cardiac allograft rejection. We tested the hypotheses that (1) radiolabeled antibody to MHC-II antigen allows detection of cardiac allograft rejection using nuclear imaging techniques and (2) uptake of radiolabeled antibody to MHC-II antigen correlates with severity of rejection. METHODS AND RESULTS: Thirteen beagles with cervical cardiac allografts were studied for 64+/-23 days by use of myocardial biopsy and in vivo imaging. Uptake of radiolabeled (131I [n=2], 123I [n=1], or 111In [n=10]) antibody to MHC-II increased over baseline in 7 animals that developed histological evidence of progressively worsening allograft rejection (group A), from 72.2+/-46.1 to 176.8+/-102.0 counts/pixel/mCi (P<.009). In 4 beagles without progressively worsening allograft rejection (group B), uptake was unchanged during follow-up (74.4+/-43.8 and 60.2+/-37.4 counts/pixel/mCi; P=NS). In animals studied with 111In-labeled antibody, uptake increased from 102.9+/-23.1 at baseline to 233.2+/-82.7 counts/pixel/mCi at follow-up in group A animals (P=.036), with no significant change in group B (91.1+/-34.9 and 75.9+/-24.9 counts/pixel/mCi; P=NS). Uptake of 111In-labeled antibody was 107.5+/-35.7, 135.9+/-70.8, and 307.8+/-90.1 counts/pixel/mCi in biopsy samples showing evidence of mild, moderate, and severe rejection, respectively (P=.001). Biopsy samples showing mild, moderate, and intense MHC-II expression antibody uptake had uptakes of 92.6+/-36.3, 158.5+/-54.7, and 307.8+/-90.1 counts/pixel/mCi, respectively (P=.00004). CONCLUSIONS: Radiolabeled monoclonal antibodies to MHC-II antigen can detect cardiac allograft rejection in this large mammal model of cardiac allograft transplantation, and this technique may have a potential role in the detection of rejection in patients after cardiac transplantation.     

Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings

Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [99mTc(V)-DMSA] and receptor ([111In-DTPA-D-Phe1]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither 99mTc(V)-DMSA nor [111In-DTPA-D-Phe1]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC.     

Proximal sciatic axotomy does not inhibit the induction of neurofilamentous inclusions following intracisternal aluminum chloride exposure

The present study evaluated 99mTc(V) DMSA as an agent for the visualization of inflammatory lesions in comparison to 99mTc(III) DMSA and 99mTC-HIG. All three radiopharmaceuticals were prepared with commercial kits. 99mTc(V) DMSA was prepared at neutral pH by the addition of first bicarbonate and then pertechnetate to the kit contents. The labeling efficiency was 99% as determined by ITLC. Abscesses were induced by i.m. injection of 50 microliters turpentine into the right thighs of 36 Swiss albino mice. Six days later 3.7 MBq of each radiopharmaceutical was i.v. administered to 12 mice. The mice were sacrificed at 1, 3, 6 and 24 h later. Scintigrams were obtained with a gamma camera. The abscesses were better visualized on scintigrams with 99mTc(V) DMSA compared to 99mTc(III) DMSA, starting at 1 h. The animals were dissected and the organs were removed, weighed and the radioactivity determined with a gamma counter. The abscess to other tissue ratios were higher with 99mTc(V) DMSA than the other radiopharmaceuticals. The max. abscess/muscle ratios were 9.46 +/- 3.20 (24 h), 4.19 +/- 1.39 (6 h) and 5.98 +/- 1.17 (24 h) and max. abscess/blood ratios were 6.22 +/- 1.41, 4.09 +/- 0.84 and 0.914 +/- 0.351 all at 24 h for 99mTc(V) DMSA, 99mTc(III) DMSA and 99mTc-HIG, respectively. Experimental arthritis was produced in New Zealand white rabbits by intra-articular injection of ovalbumin. Four days later 37 MBq of 99mTc(V) DMSA and 99mTc-HIG were each i.v. administered to 3 rabbits. Scintigrams obtained at 1, 3, 6, and 24 h clearly demonstrated arthritic joints. ROI's over arthritic joints were compared to contralateral normal joints (A/C). The max. A/C ratios were 2.10 +/- 0.31 (3 h) and 2.92 +/- 0.99 (24 h) for 99mTc(V) DMSA and 99mTc-HIG, respectively. Our results indicated the feasibility of imaging inflammatory lesions with 99mTc(V) DMSA.     

Health insurance coverage and outcome following acute myocardial infarction. A community-wide perspective

The potential of scintigraphy with technetium 99m-labelled J001 (99mTc-J001) to detect synovitis was studied in 15 rabbits with osteoarthritis (OA) of the right knee (section of cruciate ligaments), in five sham-operated rabbits and in four non-operated rabbits. J001 is a non-pyrogenic, acylated poly (1,3) galactoside isolated from the membrane of a non-pathogenic strain of Klebsiella pneumoniae which is able to bind selectively to macrophages via the binding to CD11b and CD14 molecules. The results of 99mTc-J001 scintigraphy were compared with those of scintigraphy with 99mTc-labelled methylene diphosphonate (99mTc-MDP) and GC-APG (a derivative of J001 unable to bind macrophages in vitro). The mean scintigraphic ratios (diseased healthy knee) of 99mTc-J001 were significantly higher in OA rabbits than in sham- and non-operated rabbits, from as early as day 18 until day 90. 99mTc-J001 scintigraphy demonstrated earlier increased uptake than 99mTc-MDP scintigraphy. The mean scintigraphic ratios of 99mTc-J001 were significantly higher than those of 99mTc-GC-APG (which remained normal) in OA rabbits. The normal scintigraphic ratios of 99mTc-J001 in sham-operated and non-operated rabbits, as well as of 99mTc-GC-APG in OA rabbits, suggested that the increased uptake demonstrated with 99mTc-J001 in OA rabbits, as early as day 18 corresponded to imaging of synovitis via elective macrophage targeting. These results showed that 99mTc-J001 scintigraphy should be a specific method of detecting synovitis in OA.     

Gallium-67 scintigraphy in lymphoma with bone involvement

Both Hodgkin's and non-Hodgkin's lymphoma (NHL) may involve bone. Traditionally, 99mTc-MDP bone scintigraphy has been used to detect such involvement. In recent years, 67Ga scintigraphy has shown to be useful in monitoring treatment response in lymphoma. Although 99mTc-MDP has not been found particularly useful for monitoring bone response to cancer treatment, we were interested in whether 67Ga scintigraphy and SPECT could be used to monitor bone involvement with lymphoma. METHODS: Gallium-67 and 99mTc-MDP uptake were investigated in 20 patients with lymphoma involving the bone before treatment. Gallium-67 scans were done in 16 patients for monitoring response to treatment in the bone lesions. RESULTS: Gallium-67 studies diagnosed bone lesions in 19 of the 20 patients. Technetium-99m-MDP detected bone lesions in all patients investigated. In four patients, uptake by Ga-67 was more intense than 99mTc-MDP and in another four patients 99mTc-MDP uptake was more evident. Gallium-67, however, was useful in detecting other regions of involvement in 18 of the 19 patients with soft-tissue lymphoma lesions. Gallium-67 scintigraphy also correctly monitored bone response to treatment in all but one of the 16 patients who had 67Ga scintigraphy after completing therapy. CONCLUSION: Gallium-67 uptake by lymphoma involving the bone can be used to monitor osseous response to treatment.     

Biodistribution and dosimetry of TRODAT-1: a technetium-99m tropane for imaging dopamine transporters

Technetium-99m TRODAT-1 is an analog of cocaine that selectively binds the presynaptic dopamine transporters. The primary purpose of this study was to measure its whole-body biokinetics and radiation dosimetry in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacological safety to be assessed simultaneously. METHODS: The sample included 4 men and 6 women ranging in age from 22-54 yr. An average of 20 whole-body scans were acquired sequentially on a dual-head camera for up to 46 hr after the intravenous administration of 370+/-16 MBq (10.0+/-0.42 mCi) 99mTc TRODAT. The renal excretion fractions were measured from 12-24 discrete urine specimens. The fraction of the administered dose in 17 regions of interest and each urine specimen was quantified from the attenuation and background corrected geometric mean counts in conjugate views. Multiexponential functions were iteratively fit to each time-activity curve using a nonlinear, least squares regression algorithm. These curves were numerically integrated to yield source organ residence times. Gender-specific radiation doses were then estimated with the Medical Internal Radiation Dose technique for each subject individually before any results were averaged. RESULTS: There were no pharmacological effects of the radiotracer on any of the subjects. The early planar images showed differentially increased activity in the nose, pudendum and stomach. SPECT images demonstrated that the radiopharmaceutical localized in the basal ganglia in a distribution that was consistent with selective transporter binding. Image analysis showed that the kidneys excreted between 20% and 32% of the injected dose during the first 22-28 hr postadministration, after which no more activity could be recovered in the urine. The dose limiting organ in both men and women was the liver, which received an average of 0.046 mGy/MBq (0.17 rads/mCi, range 0.14-0.22 rad/mCi). In the worst case, which was clearly an over-estimation, it would have taken 22.7 mCi to deliver 5 rad to the liver. CONCLUSION: TRODAT may be a safe and effective radiotracer for imaging dopamine transporters in the brain and the body.     

Fluorine-18-FDG PET and technetium-99m antigranulocyte antibody scintigraphy in chronic osteomyelitis

The aim of this study was to assess the usefulness of PET with 2-18F-fluoro-2-deoxy-D-glucose (FDG), as compared to immunoscintigraphy (IS) with 99mTc-labeled monoclonal antigranulocyte antibodies (AGAbs), in the detection of chronic osteomyelitis. METHODS: Fifty-one patients suspected of having chronic osteomyelitis in the peripheral (n = 36) or central (n = 15) skeleton were evaluated prospectively with static FDG PET imaging and combined 99mTc-AGAb/99mTc-methylene diphosphonate (MDP) bone scanning within 5 days. FDG PET and IS were evaluated in a blinded and independent manner by visual interpretation, which was graded on a five-point scale of two observers' confident diagnosis of osteomyelitis. Receiver operating characteristic (ROC) curve analysis was performed for both imaging modalities. The final diagnosis was established by means of bacteriologic culture of surgical specimens and histopathologic analysis (n = 31) or by biopsy and clinical follow-up over 2 yr (n = 20). RESULTS: Of 51 patients, 28 had osteomyelitis and 23 did not. According to the unanimous evaluation of both readers, FDG PET correctly identified 27 of the 28 positives and 22 of the 23 negatives (IS identified 15 of 28 positives and 17 of 23 negatives, respectively). The area under the ROC curve was 0.97/0.97 (reader 1/reader 2) for FDG PET and 0.87/0.90 for IS, with a high degree of interobserver concordance (K-values were 0.96 for FDG PET and 0.91 for IS). In the central skeleton, the ROC curve area was 0.98/1.00 for FDG PET and 0.71/0.77 for IS (p<0.05). On the basis of ROC analysis, the overall accuracies of FDG PET and IS in the detection of chronic osteomyelitis were 96%/96% and 82%/ 88%, respectively. With regard to the optimal threshold values, sensitivity and specificity were 100%/97% and 95%/95% with FDG PET, compared to 86%/92% and 77%/82% with IS, respectively. CONCLUSION: In the peripheral skeleton, both FDG PET and combined 99mTc-AGAb/99mTc-MDP scanning are appropriate imaging modalities to diagnose chronic osteomyelitis. FDG PET additionally allows reliable differentiation between osteomyelitis and infection of the surrounding soft tissue. In the central skeleton within active bone marrow, FDG PET is highly accurate and superior to AGAb imaging in the diagnosis of chronic osteomyelitis, which frequently presents as a nonspecific photopenic lesion at scintigraphy with labeled white blood cells.     

Relationship between symptoms of jumper''s knee and the ultrasound characteristics of the patellar tendon among high level male volleyball players

In this study we investigated the applicability of 99mTc-labeled CD19 monoclonal antibody (mAb) for tumor imaging in patients with B cell non-Hodgkin's lymphoma. A 1-mg sample of murine CD19 mAb was labeled with approximately 550 MBq [99mTc]pertechnetate. The labeled mAb was administered i.v. to seven patients, four without and three with pretreatment with 10 mg unlabeled CD19 mAb. The number of circulating B cells was decreased by 44 +/- 5% 1 h after injection of the radiolabeled mAb. Peripheral B cells were coated with CD19, resulting in partial modulation of CD19, most pronounced in the three pretreated patients. Whole-body images were obtained with a gamma camera and compared with results obtained by conventional imaging techniques. Initially, blood-pool activity dominated, whereas 24 h after injection the radioactivity was mainly located in the spleen, kidneys and liver. In two patients, a lesion in the spleen appeared as an unlabeled spot. In one patient, a lesion in the femur, which was detected by computed tomography (CT) and gallium-67 scans, was also seen on the CD19 scan from 1 h after administration of the radioimmunoconjugate onwards. Good imaging of bone marrow infiltration was observed in one of three patients. Lymph node involvement was not observed in any of the patients in whom affected lymph nodes were detected by CT or gallium-67 scan. In conclusion, in the present study radioimmunodetection with 99mTc-labeled CD19 mAb was found to be inferior to CT and gallium-67 scanning in the diagnosis of patients with B cell non-Hodgkin's lymphoma.     

Dependence of microwave produced heating of cell suspensions on their concentration

This study compared three radionuclide techniques in distinguishing musculoskeletal infection from noninfectious inflammation. METHODS: Thirty-five orthopedic patients with suspected musculoskeletal infection were examined using three radionuclide techniques in sequence: triphasic bone scintigraphy, 99mTc radioleukocytes (99mTc-WBC) scintigraphy and 99mTc human immunoglobulin (99mTc-Hig) scintigraphy. Two "early" and "late" acquisitions were performed, at 4-6 hr and 20-24 hr postinjection, respectively. Patients who were diagnosed as suffering from noninflammatory lesions became the controls. We calcu"late"d for all studies one index of inflammation (Infl) as the ratio between counts in the uptake area and counts in an equal area of normal tissue. RESULTS: The "early" radiolabeled leukocytes and "late" Hig scintigraphy allowed the greatest ability to distinguish between infections and noninfectious inflammations (p < 0.011 and p < 0.016) with a sensitivity of 96.6% and 96.5% and specificity of 71% and 100%, respectively. Hig and radioleukocytes allowed distinguishing infections from noninflammatory diseases at both examinations. CONCLUSION: The "early" radioleukocyte scintigraphy allowed us to separate infections from noninfectious inflammations. In contrast, the same result can be obtained only with the "late" scan in the Hig study, but Hig mapped the spread of the inflammation into soft tissues better. Hig might be an alternative to radioleukocytes because of its simple preparation, similar accuracy and safety.     

Mapping the in vivo distribution of herpes simplex virions

We describe a method for labeling enveloped viral particles with a radiotracer, indium-111, allowing labeled viruses to be traced in vivo by nuclear imaging. After initial optimization experiments, a labeling efficiency of 83% (incorporation yield) was achieved for herpes simplex virus (HSV), resulting in a specific activity of 30 microCi/10(9) PFU. The labeling procedure did not significantly reduce the infectivity of the labeled virus and the virus did not release any significant amounts of the radionuclide within 12 hr after labeling. Sequential imaging of animals after intravenous administration of the labeled virus showed fast accumulation in the liver and redistribution from the blood pool (immediately after injection) to liver and spleen (12-24 hr after injection). At 12 hr after injection 7% of the virus-associated (111)In had been eliminated from the body and the remaining organ distribution of the virus was as follows: spleen 2.87 +/- 0.54% ID/g; liver, 2.60 +/- 0.51% ID/g; kidney, 0.98 +/- 0.31% ID/g; lung, 0.57 +/- 0.10% ID/g; [corrected] and lower amounts in other organs. Our results indicate that the described method allows qualitative and quantitative assessment of viral biodistribution in vivo by nuclear imaging.     

Dosimetry of rhenium-186-labeled monoclonal antibodies: methods, prediction from technetium-99m-labeled antibodies and results of phase I trials

Rhenium-186 is a beta-emitting radionuclide that has been studied for applications in radioimmunotherapy. Its 137 keV gamma photon is ideal for imaging the biodistribution of the immunoconjugates and for obtaining gamma camera data for estimation of dosimetry. Methods used for determining radiation absorbed dose are described. We have estimated absorbed dose to normal organs and tumors following administration of two different 186Re-labeled immunoconjugates, intact NR-LU-10 antibody and the F(ab')2 fragment of NR-CO-02. Tumor dose estimates in 46 patients varied over a wide range, 0.4-18.6 rads/mCi, but were similar in both studies. Accuracy of activity estimates in superficial tumors was confirmed by biopsy. Prediction of 186Re dosimetry from a prior 99mTc imaging study using a tracer dose of antibody was attempted in the NR-CO-02 (Fab')2 study. Although 99mTc was an accurate predictor of tumor localization and the mean predicted and observed radiation absorbed doses to normal organs compared favorably, 186Re dosimetry could not be reliably predicted in individual patients. The methods described nevertheless provide adequate estimates of 186Re dosimetry to tumor and normal organs.     

Retention of soluble 99mTc-DTPA in the human lung: 24-h postdeposition

Clearance of low-molecular-weight solutes, e.g., radiolabeled chelate diethylenetriaminepentaacetate (DTPA), across epithelial surfaces of distal airways and the lung parenchyma is a broadly used technique to assess epithelial integrity. It has been generally assumed that clearance of solute follows a simple first-order process and that DTPA clearance through the respiratory epithelium and into blood and lymphatic channels is complete within a few hours. Using gamma-camera imaging and a radiolabeled aerosol of 99mTc-labeled DTPA, we observed in eight healthy subjects lung retention of radioisotope approximately 24 h postdeposition of the 99mTc-DTPA. Residual lung retention at the 24-h end point averaged 6.0 +/- 1.8 (SD)% of the amount of radioisotope initially deposited in the lung. This suggests that for normal healthy subjects a small amount of the 99mTc radioisotope, either in a dissociated or chelated form, is nonpermeable or slowly cleared from respiratory tisssues.     

Gallium-67 radiotoxicity in human U937 lymphoma cells

Promising clinical results have been obtained with radiolabeled antibodies in lymphoma patients. The higher uptake by lymphomas of 67Gallium (67Ga) compared with monoclonal antibodies makes selective radiotherapy by the widely available 67Ga appealing. However, the gamma radiation of 67Ga used in scintigraphy is considered to be almost non-toxic to lymphoma cells. However, in addition to photon radiation 67Ga emits low energy Auger electrons and 80-90 keV conversion electrons which could be cytotoxic. The objective of the present study was the assessment of radiotoxicity of 67Ga on a lymphoid cell line: U937. Proliferation (MTT-assay) and clonogenic capacity (CFU-assay) were measured after 3 and 6 days incubation with 10, 20 and 40 microCi ml-1 67Ga. Growth inhibition was 36% after 3 days incubation and 63% after 6 days incubation with 40 microCi 67Ga ml-1. Clonogenic capacity was reduced by 51% after 3 days and 72% after 6 days incubation with 40 microCi ml-1 67Ga. A survival curve showed an initial shoulder and became steeper beyond 200-250 pCi cell-1 (low linear energy transfer type). Iso-effect doses of 67Ga and 90Yttrium (90Y) were determined. The iso-effect dose of 40 microCi 67Ga ml-1 (cumulative dose of conversion electrons 306 cGy) was 2.5 microCi 90Y ml-1 (cumulative dose 494 cGy) and the iso-effect dose of 80 microCi 67Ga ml-1 was 5.0 microCi 90Y/ml. The main cytotoxic effect of 67Ga seems to be induced by the 80 keV conversion electrons. We conclude that the conversion electrons of 67Ga have a cytotoxic effect on U937 cells and that in our experiments a 16-fold higher microCi-dose of 67Ga than of 90Y was needed for the same cytotoxic effect. We believe that 67Ga holds promise for therapeutic use.     

Temporal and spatial expression of the E5a protein during the differentiation-dependent life cycle of human papillomavirus type 31b

Nalpha-for-Nle-Leu-Phe-Nle-Tyr-Lys, a chemotactic peptide that binds with high affinity to the chemoattractant receptor on granulocytes and monocytes, was labeled with 99mTc using the diaminedithiol (DADT) chelating system to coordinate the Tc. 99mTc labeling of the DADT-coupled peptide was accomplished in 84% overall yield (room temperature for 10 min) using [99mTc]glucoheptonate as the donor of prereduced Tc. HPLC analysis showed two major 99mTc-labeled peptide peaks, 99mTc-DADT-Pep-I and 99mTc-DADT-Pep-II, were obtained in a ratio of 1:0.85. Using an iodoacetamide-derivatized gel to remove unlabeled peptide from the 99mTc labeling mixtures, essentially no-carrier-added (nca) high-specific activity 99mTc-labeled chemotactic peptides were obtained. The 99Tc analogues of the peptides were synthesized (72% yield) in a similar fashion and correlated with 99mTc complexes I and II by HPLC. In vitro competitive receptor binding assays of the isolated 99Tc analogues were performed against the tritiated chemotactic peptide [3H]N-for-Met-Leu-Phe ([3H]fMLF) using isolated granulocytes. The 99Tc-derivatized peptides showed similar binding affinities to the chemoattractant receptor as the unlabeled Nalpha-for-Nle-Leu-Phe-Nle-Tyr-Lys. The nca 99mTc-labeled peptides gave high contrast images of experimental inflammation in rabbits without causing neutropenia. Thus, it is feasible to attach the Tc-DADT chelate to low-molecular weight receptor binding chemotactic peptides and retain substantial binding to the receptor. Chemotactic peptides labeled with 99mTc via the DADT ligand system have the potential for imaging focal sites of inflammation without toxic effects, an important consideration in the successful utilization of chemotactic peptide agonists.