EuropeanJournalof
Nuclear Medicine
Original article
Detection of inflammatory lesions with radiolabelled immunoglobulins D. B l o k 1'2, M. v. O g t r o p 3, J.W. A r n d P , J.A.J. C a m p s ~, R.I.J. F e i t s m a 1, W. G o e d e m a n s 4, a n d E.K.J. P a u w e l s ~ Departments of 1 Diagnostic Radiology, Division of Nuclear Medicine, 2 Clinical Pharmacy and Toxicology, a Infectious Diseases, University Hospital Leiden, 2333 AA Leiden, The Netherlands and 4 Mallinckrodt Diagnostica Holland BV., 1755 ZG Petten, The Netherlands Received February 4, 1989 and in revised July 27, 1989
Abstract. Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials of Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection were injected with Tc 99m-immunoglobulin, Tc 99m-albumin or gallium citrate G a 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with gallium. " Key words: Immunoglobulins - Infection tion - 9 9 m T c labelling
Inflamma-
Tc 99m HMPAO-labelled WBC for the localisation of abscesses and inflammatory lesions ( C r a m a - B o h b o u t h et al. 1988; Peters et al. 1986; Roddie et al. 1988). More recently, monoclonal antibodies (MoAbs) directed against granulocytes have become available for radioimmunodetection. Promising as well as disappointing results have been reported with iodine 123- and technetium Tc 99m-labelled MoAbs (Locher et al. 1986; Vorne et al. 1988). In addition, it has been demonstrated that nonspecific polyclonal immunoglobulins (Ig) radiolabelled with indium 111 also accumulate in focal sites of infection (Fischman et al. 1988a, b; Rubin et al. 1988). To explore the influence of the labelling procedure and the usefulness of technetium Tc 99m-labelled aspecific Ig in the localisation of infectious foci, we performed a pilot study with Tc 99m-albumin, gallium citrate G a 67 and three preparations of Tc 99m-Ig in an animal model.
Eur J Nuel Med (1990) 16:303-305 Materials
Introduction
In nuclear medicine several techniques are used in the diagnosis of inflammatory diseases. Gallium citrate G a 67 is frequently used, but its inferior radiation and dosimetry characteristics and lack of specificity for inflammation or infection limit its applicability. Radiolabelling of autologous mixed leucocytes or granulocytes is an established procedure in clinical nuclear medicine. Although the labelling of blood components remains complex and time-consuming, indium 111 tropolone-labelled granulocytes are routinely used for the detection of inflammatory bowel disease, as are technetium Offprint requests to .' D. Blok
and methods
Labelling and administration. For the preparation of Tc 99m-albumin, we used a Iyophilised kit (Solco Nuclear) with 10 mg albumin (HSA) and 1 mg SnC12.2HzO. After the addition and incubation of 2 ml sodium pertechnetate Tc 99 m (350 MBq), an aliquot containing approx. 500 gg HSA and 15 MBq Tc 99m-albumin was given to each animal. Immunoglobulin (human Ig for intravenous use; CLB, Amsterdam, The Netherlands) was labelled using three different techniques. Tc 99m-Ig (I) was prepared with a protein-labelling technique as previously described (Blok etal. 1989; Feitsma et al. 1987). Briefly, a mixture of sodium pertechnate Tc 99m (500 gl in normal saline), dimethylformamide (27 ~tl)and 5 N hydrochloric acid (7 gl) was heated at 140° C for 4 h. The remaining dry residue was extracted with chloroform (500 gl). The chloroform solution containing the technetium Tc 99m activity was transferred to another tube and evaporated to dryness; then, 500 gl of the Ig solution (10 mg/ml) was added to the dry intermediate and incubated at 40° C for 60 min.
© Springer-Verlag 1990
304
For the preparation of Tc 99m-Ig (II) we used a modification of the above method. Instead of dimethylformamide, hydroxylamine hydrochloride (i p~g)was taken and the technetium Tc 99m intermediate was formed within 10 min at 140° C. Again, the intermediate was extracted with chloroform, evaporated and incubated with Ig solution. Tc 99m-Ig (III) was prepared from a lyophilised kit containing a modified Ig (1 mg Ig). Briefly, Ig was incubated with 2-iminothiolane for 30 rain in a molar ratio of 1:15. Unreacted 2-iminothiolane was removed from Ig by gelchromatography. The preparation was lyophilised with stannous tartrate and reconstituted with sodium pertechnetate Tc 99m. All Ig preparations were purified by size-exclusion chromatography on a 5 x 1 cm Sephadex G50 column. Analysis on a 30 x 1 cm Superose 12 column demonstrated labelled Ig without measurable aggregation or fractionation. From the purified sample, 50 500 gg Ig with an activity of 10-30 MBq was injected. Animal model. Female specific-pathogen-free Swiss mice weighing
Numbers in parentheses represent the standard deviation (n=3 or 4)
25-30 g (Broekman Institutes, Someren, The Netherlands) were used throughout the study. Staphylococcus aureus ATCC 25923 from the American Type Culture Collection (Rockville, Md, USA) was used as the test Strain. An overnight culture of the bacterium was prepared in Brain Heart Infusion broth (Oxoid, Basingstoke, UK), snap-frozen in liquid nitrogen and stored at - 7 0 ° C. Before each experiment aliquots were thawed at 37° C. Mice were infected by injecting 0,1 ml of a 1 : 10 dilution of the overnight culture of S. aureus into the thigh muscle of the right leg (total number of viable bacteria injected, 8 × 106 colony-forming units). The infection was allowed to develop for 18 h. At 18 h after inoculation with S. aureus, the mice were anaesthetized. For each radiopharmaceutical, four mice were injected intravenously in the ventral tail vein with 10-30 MBq technetium Tc99m-labelled protein or 4 MBq gallium citrate Ga 67 (Mallinckrodt Diagnostica, Petten, The Netherlands). Scintigraphy. At 1, 6 and 24 h after the intravenous injection of the radiopharmaceutical, scintigraphy was performed. A smallfield-view gamma camera (Toshiba GCA 102S, Tokyo, Japan) with a high resolution, low-energy, parallel-hole collimator was used for imaging. The gamma camera was connected to a dedicated computer system (MDS-A 2, Ann Arbor, Mich, USA) and images were stored in a 256 × 256 matrix. The energy was set at 140 keV with a window of 20% for imaging technetium Tc 99m compounds. For the experiment with gallium citrate Ga 67, two peaks were selected (185 and 300 keV included in one broad window) and a medium-energy collimator was mounted. Acquisition was terminated after collection of 500,000 counts. Scintigrams were evaluated in a qualitative as well as quantitative way. Regions of interest were drawn over the infected right limb and over an equivalent part of the contra-lateral site, from which right:left ratios were calculated. Images (1, 6 and 24 h) were qualitatively considered by three observers for visibility of the infection site and image quality. Scintigrams could be scored as inferior (1), mediocre (2), good (3) or superior (4). Scores were averaged and normalized from 0 to 1.
Results and discussion In Table 1 the q u a n t i t a t i v e i n t e r p r e t a t i o n o f the i m a g e s is given. F o r e a c h o f the five p r e p a r a t i o n s , f o u r mice were injected; in t w o cases, o n l y three mice were evalu-
Table 1. Target:non-target ratios for five different radiolabelled preparations at 1,6 and 24 h after injection lh
6h
24h
Gallium citrate Ga 67
1.6 (0.2)
1.9 (0.2)
1.9 (0.3)
Albumin Tc 99m
2.5 (0.7)
2.8 (1.3)
4.3 (1.8)
Immunoglobulin Tc 99m-Ig (I)
4.2 (1.2)
6.1 (1.6)
6.1 (1.0)
Immunoglobulin Tc 99m-Ig (II)
2.8 (0.2)
3.3 (1.0)
4.5 (0.8)
Immunoglobulin Tc 99m-Ig (III)
3.3 (1.0)
3.8 (0.9)
6.6 (1.3)
Table 2. Average normalized scores of the scintigrams at 1,6 and
24 h after injection lh
6h
24h
Gallium citrate Ga 67
0.25
0.35
0.35
Albumin Tc 99m
0.50
0.65
0.75
Immunoglobulin Tc 99m-Ig (I)
0.65
0.90
1.00
Immunoglobulin Tc 99m-Ig (II)
0.50
0.75
0.85
Immunoglobulin Tc 99m-Ig (III)
0.65
0.90
1.00
For scoring of the image quality and the visualisation of the infection, 0 represented inferior quality and 1, superior quality
able due to e x t r a v a s a t i o n . A t I h after injection, the targ e t : n o n - t a r g e t r a t i o c a l c u l a t e d using the H S A a n d Ig p r e p a r a t i o n s was slightly e n h a n c e d c o m p a r e d w i t h t h a t o b t a i n e d using gallium. F o r Ig (I) a n d (III), a c c u m u l a tion in the infected r e g i o n was evident, especially on the 6- a n d 24-h i m a g e s ; Ig (II) was inferior to Ig (I) a n d (III) a n d c o m p a r a b l e w i t h H S A . Table 2 shows the a v e r a g e n o r m a l i z e d scores r e c o r d e d b y the three o b s e r v ers. These o b s e r v a t i o n s c o r r e l a t e well with the t a r g e t : n o n - t a r g e t r a t i o s in Table 1. In Fig. I the 6-h i m a g e s o f the five r a d i o p h a r m a c e u t i cals are presented. Besides the b l a d d e r a n d liver, w h i c h were quite clearly labelled b y the p r o t e i n p r e p a r a t i o n s , the local infection was clearly visible. F i g u r e 2 shows the time course for one o f the Tc 99m-Ig p r e p a r a t i o n s . I n c r e a s e d v a s c u l a r p e r m e a b i l i t y d u e to the i n f l a m m a t o r y p r o c e s s m a y e n h a n c e t r a c e r a c c u m u l a t i o n , b u t the imp r o v e d d e t e c t i o n o f infectious lesions b y Ig as o p p o s e d
305
Fig. 1. Scintigrams of mice (posterior views) 6 h after the administration of a gallium citrate Ga 67, b Tc 99m-albumin, e Tc 99m-ig (I), d Tc 99m-Ig (II), and e Tc 99m-Ig (III)
References
Fig. 2. Scintigrams of a mouse (posterior view) injected with Tc 99m-Ig (I) at a 1, b 6, and e 24 h after administration
to H S A suggests that localisation is mediated by an additional c o m p o n e n t . The a b u n d a n c e o f F c receptors in i n f l a m m a t o r y processes p r o b a b l y plays a role in the a c c u m u l a t i o n o f labelled Ig. F i s c h m a n et al. (1988a) previously d e m o n strated e n h a n c e d localisation o f intact Ig as well as Fc fragments in focal sites o f infection, whereas Fab localisation was minimal. Tc 99m-Ig m a y be an attractive alternative in the clinical diagnosis o f occult i n f l a m m a t o r y processes. A ready-to-use r a d i o p h a r m a c e u t i c a l labelled with technetium Tc 99m offers clear advantages over radiolabelling o f autologous b l o o d c o m p o n e n t s as well as over gallium citrate G a 67. We conclude f r o m this pilot experiment that Tc 99m-Ig scintigraphy is superior to that using gallium citrate G a 67. F u r t h e r experiments with various Tc 99m-Ig preparations are in progress and should t h r o w light on the m e c h a n i s m o f localisation and its clinical usefulness.
Blok D, Feitsma RIJ, Wasser MNJM, Nieuwenhuizen W, Pauwels EKJ (~[989) A new method for protein labeling with 99~Tc. Nucl Med Biol 16:11 t 6 Crama-Bohboutz GE, Arndt JW, Pena AS, Verspaget HW, Thon A, Tham RTO, Weterman IT, Pauwels EKJ, Lamers CBHW (1988) Value of Indium-i 11 granulocyte scintigraphy in the assessment of Crohn's disease of the small intestine. Digestion 40: 227-236 Feitsma RIJ, Blok D, Wasser MNJM, Nieuwenhuizen W, Pauwels EKJ (1987) A new method for 99mTc-labetling of proteins with an application to clot detection with an antifibrin monoclonal antibody. Nucl Med Commun 8 : 771-777 Fischman AJ, Wilkinson R, Khaw BA, Callahan RJ, Ahmad M, Locke E, Nossiff ND, Strauss HW, Rubin RH (I988a) Imaging of localized bacterial infections with radiolabeled non-specific antibody fragments. J Nucl Med 29:610 (abstr) Fischman AJ, Rubin RH, Khaw BA, Callahan RJ, Wilkinson R, Keech F, Nedelman M, Dragotakes S, Kramer PB, LaMuragia GM, Lind S, Strauss HW (1988 b) Detection of acute inflammation with ~11in_1abeled nonspecific polyclonal IgG. Semin Nucl Med 28 : 335-344 Locher JTh, Seybold K, Andres R, Schubiger PA, Mach JP, Buchegger F (1986) Imaging of inflammatory and infectious lesions after injection of radioiodinated monoclonal anti-granuIocytes antibodies. Nucl Med Commun 7:659-670 Peters AM, Osman S, Henderson BL, Kelly JD, Danpure H J, Hawker R J, Hodgson H J, Neirinckx RD, Lavender JP (1986) Clinical experience with 99~Tc-hexamethylpropyleneamineoxime for labelling leucocytes and imaging inflammation. Lancet ii : 946-949 Roddie ME, Peters AM, Danpure H J, Osman S, Henderson BL, Lavender PJ, Carroll M J, Neirinckx RD, Kelly JD (1988) Inflamation : imaging with 99mTc-HMPAO-labeled leucocytes. Radiology 166:767-772 Rubin RH, Young LS, Hansen WP, Nedehnan M, Wilkinson R, Nelles M J, Callahan R, Khaw BA, Strauss HW (I988) Specific and nonspecific imaging of localized Fischer immunotype 1 Pseudomonas aeruginosa infection with radiolabeled monoclonal antibody. J Nucl Med 29:651-656 Vorne M, Karhunen K, Lantto T, Mokka R, Mfikelfi P, Nikoskelainen J, Rajamfiki A (1988) Comparison of x23I monoclonal granulocyte antibody and 99~Tc-HMPAO-labelled leucocytes in the detection of inflammation. Nucl Med Commun 9 : 623-629
Nuclear Medicine
Original article
Detection of inflammatory lesions with radiolabelled immunoglobulins D. B l o k 1'2, M. v. O g t r o p 3, J.W. A r n d P , J.A.J. C a m p s ~, R.I.J. F e i t s m a 1, W. G o e d e m a n s 4, a n d E.K.J. P a u w e l s ~ Departments of 1 Diagnostic Radiology, Division of Nuclear Medicine, 2 Clinical Pharmacy and Toxicology, a Infectious Diseases, University Hospital Leiden, 2333 AA Leiden, The Netherlands and 4 Mallinckrodt Diagnostica Holland BV., 1755 ZG Petten, The Netherlands Received February 4, 1989 and in revised July 27, 1989
Abstract. Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials of Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection were injected with Tc 99m-immunoglobulin, Tc 99m-albumin or gallium citrate G a 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with gallium. " Key words: Immunoglobulins - Infection tion - 9 9 m T c labelling
Inflamma-
Tc 99m HMPAO-labelled WBC for the localisation of abscesses and inflammatory lesions ( C r a m a - B o h b o u t h et al. 1988; Peters et al. 1986; Roddie et al. 1988). More recently, monoclonal antibodies (MoAbs) directed against granulocytes have become available for radioimmunodetection. Promising as well as disappointing results have been reported with iodine 123- and technetium Tc 99m-labelled MoAbs (Locher et al. 1986; Vorne et al. 1988). In addition, it has been demonstrated that nonspecific polyclonal immunoglobulins (Ig) radiolabelled with indium 111 also accumulate in focal sites of infection (Fischman et al. 1988a, b; Rubin et al. 1988). To explore the influence of the labelling procedure and the usefulness of technetium Tc 99m-labelled aspecific Ig in the localisation of infectious foci, we performed a pilot study with Tc 99m-albumin, gallium citrate G a 67 and three preparations of Tc 99m-Ig in an animal model.
Eur J Nuel Med (1990) 16:303-305 Materials
Introduction
In nuclear medicine several techniques are used in the diagnosis of inflammatory diseases. Gallium citrate G a 67 is frequently used, but its inferior radiation and dosimetry characteristics and lack of specificity for inflammation or infection limit its applicability. Radiolabelling of autologous mixed leucocytes or granulocytes is an established procedure in clinical nuclear medicine. Although the labelling of blood components remains complex and time-consuming, indium 111 tropolone-labelled granulocytes are routinely used for the detection of inflammatory bowel disease, as are technetium Offprint requests to .' D. Blok
and methods
Labelling and administration. For the preparation of Tc 99m-albumin, we used a Iyophilised kit (Solco Nuclear) with 10 mg albumin (HSA) and 1 mg SnC12.2HzO. After the addition and incubation of 2 ml sodium pertechnetate Tc 99 m (350 MBq), an aliquot containing approx. 500 gg HSA and 15 MBq Tc 99m-albumin was given to each animal. Immunoglobulin (human Ig for intravenous use; CLB, Amsterdam, The Netherlands) was labelled using three different techniques. Tc 99m-Ig (I) was prepared with a protein-labelling technique as previously described (Blok etal. 1989; Feitsma et al. 1987). Briefly, a mixture of sodium pertechnate Tc 99m (500 gl in normal saline), dimethylformamide (27 ~tl)and 5 N hydrochloric acid (7 gl) was heated at 140° C for 4 h. The remaining dry residue was extracted with chloroform (500 gl). The chloroform solution containing the technetium Tc 99m activity was transferred to another tube and evaporated to dryness; then, 500 gl of the Ig solution (10 mg/ml) was added to the dry intermediate and incubated at 40° C for 60 min.
© Springer-Verlag 1990
304
For the preparation of Tc 99m-Ig (II) we used a modification of the above method. Instead of dimethylformamide, hydroxylamine hydrochloride (i p~g)was taken and the technetium Tc 99m intermediate was formed within 10 min at 140° C. Again, the intermediate was extracted with chloroform, evaporated and incubated with Ig solution. Tc 99m-Ig (III) was prepared from a lyophilised kit containing a modified Ig (1 mg Ig). Briefly, Ig was incubated with 2-iminothiolane for 30 rain in a molar ratio of 1:15. Unreacted 2-iminothiolane was removed from Ig by gelchromatography. The preparation was lyophilised with stannous tartrate and reconstituted with sodium pertechnetate Tc 99m. All Ig preparations were purified by size-exclusion chromatography on a 5 x 1 cm Sephadex G50 column. Analysis on a 30 x 1 cm Superose 12 column demonstrated labelled Ig without measurable aggregation or fractionation. From the purified sample, 50 500 gg Ig with an activity of 10-30 MBq was injected. Animal model. Female specific-pathogen-free Swiss mice weighing
Numbers in parentheses represent the standard deviation (n=3 or 4)
25-30 g (Broekman Institutes, Someren, The Netherlands) were used throughout the study. Staphylococcus aureus ATCC 25923 from the American Type Culture Collection (Rockville, Md, USA) was used as the test Strain. An overnight culture of the bacterium was prepared in Brain Heart Infusion broth (Oxoid, Basingstoke, UK), snap-frozen in liquid nitrogen and stored at - 7 0 ° C. Before each experiment aliquots were thawed at 37° C. Mice were infected by injecting 0,1 ml of a 1 : 10 dilution of the overnight culture of S. aureus into the thigh muscle of the right leg (total number of viable bacteria injected, 8 × 106 colony-forming units). The infection was allowed to develop for 18 h. At 18 h after inoculation with S. aureus, the mice were anaesthetized. For each radiopharmaceutical, four mice were injected intravenously in the ventral tail vein with 10-30 MBq technetium Tc99m-labelled protein or 4 MBq gallium citrate Ga 67 (Mallinckrodt Diagnostica, Petten, The Netherlands). Scintigraphy. At 1, 6 and 24 h after the intravenous injection of the radiopharmaceutical, scintigraphy was performed. A smallfield-view gamma camera (Toshiba GCA 102S, Tokyo, Japan) with a high resolution, low-energy, parallel-hole collimator was used for imaging. The gamma camera was connected to a dedicated computer system (MDS-A 2, Ann Arbor, Mich, USA) and images were stored in a 256 × 256 matrix. The energy was set at 140 keV with a window of 20% for imaging technetium Tc 99m compounds. For the experiment with gallium citrate Ga 67, two peaks were selected (185 and 300 keV included in one broad window) and a medium-energy collimator was mounted. Acquisition was terminated after collection of 500,000 counts. Scintigrams were evaluated in a qualitative as well as quantitative way. Regions of interest were drawn over the infected right limb and over an equivalent part of the contra-lateral site, from which right:left ratios were calculated. Images (1, 6 and 24 h) were qualitatively considered by three observers for visibility of the infection site and image quality. Scintigrams could be scored as inferior (1), mediocre (2), good (3) or superior (4). Scores were averaged and normalized from 0 to 1.
Results and discussion In Table 1 the q u a n t i t a t i v e i n t e r p r e t a t i o n o f the i m a g e s is given. F o r e a c h o f the five p r e p a r a t i o n s , f o u r mice were injected; in t w o cases, o n l y three mice were evalu-
Table 1. Target:non-target ratios for five different radiolabelled preparations at 1,6 and 24 h after injection lh
6h
24h
Gallium citrate Ga 67
1.6 (0.2)
1.9 (0.2)
1.9 (0.3)
Albumin Tc 99m
2.5 (0.7)
2.8 (1.3)
4.3 (1.8)
Immunoglobulin Tc 99m-Ig (I)
4.2 (1.2)
6.1 (1.6)
6.1 (1.0)
Immunoglobulin Tc 99m-Ig (II)
2.8 (0.2)
3.3 (1.0)
4.5 (0.8)
Immunoglobulin Tc 99m-Ig (III)
3.3 (1.0)
3.8 (0.9)
6.6 (1.3)
Table 2. Average normalized scores of the scintigrams at 1,6 and
24 h after injection lh
6h
24h
Gallium citrate Ga 67
0.25
0.35
0.35
Albumin Tc 99m
0.50
0.65
0.75
Immunoglobulin Tc 99m-Ig (I)
0.65
0.90
1.00
Immunoglobulin Tc 99m-Ig (II)
0.50
0.75
0.85
Immunoglobulin Tc 99m-Ig (III)
0.65
0.90
1.00
For scoring of the image quality and the visualisation of the infection, 0 represented inferior quality and 1, superior quality
able due to e x t r a v a s a t i o n . A t I h after injection, the targ e t : n o n - t a r g e t r a t i o c a l c u l a t e d using the H S A a n d Ig p r e p a r a t i o n s was slightly e n h a n c e d c o m p a r e d w i t h t h a t o b t a i n e d using gallium. F o r Ig (I) a n d (III), a c c u m u l a tion in the infected r e g i o n was evident, especially on the 6- a n d 24-h i m a g e s ; Ig (II) was inferior to Ig (I) a n d (III) a n d c o m p a r a b l e w i t h H S A . Table 2 shows the a v e r a g e n o r m a l i z e d scores r e c o r d e d b y the three o b s e r v ers. These o b s e r v a t i o n s c o r r e l a t e well with the t a r g e t : n o n - t a r g e t r a t i o s in Table 1. In Fig. I the 6-h i m a g e s o f the five r a d i o p h a r m a c e u t i cals are presented. Besides the b l a d d e r a n d liver, w h i c h were quite clearly labelled b y the p r o t e i n p r e p a r a t i o n s , the local infection was clearly visible. F i g u r e 2 shows the time course for one o f the Tc 99m-Ig p r e p a r a t i o n s . I n c r e a s e d v a s c u l a r p e r m e a b i l i t y d u e to the i n f l a m m a t o r y p r o c e s s m a y e n h a n c e t r a c e r a c c u m u l a t i o n , b u t the imp r o v e d d e t e c t i o n o f infectious lesions b y Ig as o p p o s e d
305
Fig. 1. Scintigrams of mice (posterior views) 6 h after the administration of a gallium citrate Ga 67, b Tc 99m-albumin, e Tc 99m-ig (I), d Tc 99m-Ig (II), and e Tc 99m-Ig (III)
References
Fig. 2. Scintigrams of a mouse (posterior view) injected with Tc 99m-Ig (I) at a 1, b 6, and e 24 h after administration
to H S A suggests that localisation is mediated by an additional c o m p o n e n t . The a b u n d a n c e o f F c receptors in i n f l a m m a t o r y processes p r o b a b l y plays a role in the a c c u m u l a t i o n o f labelled Ig. F i s c h m a n et al. (1988a) previously d e m o n strated e n h a n c e d localisation o f intact Ig as well as Fc fragments in focal sites o f infection, whereas Fab localisation was minimal. Tc 99m-Ig m a y be an attractive alternative in the clinical diagnosis o f occult i n f l a m m a t o r y processes. A ready-to-use r a d i o p h a r m a c e u t i c a l labelled with technetium Tc 99m offers clear advantages over radiolabelling o f autologous b l o o d c o m p o n e n t s as well as over gallium citrate G a 67. We conclude f r o m this pilot experiment that Tc 99m-Ig scintigraphy is superior to that using gallium citrate G a 67. F u r t h e r experiments with various Tc 99m-Ig preparations are in progress and should t h r o w light on the m e c h a n i s m o f localisation and its clinical usefulness.
Blok D, Feitsma RIJ, Wasser MNJM, Nieuwenhuizen W, Pauwels EKJ (~[989) A new method for protein labeling with 99~Tc. Nucl Med Biol 16:11 t 6 Crama-Bohboutz GE, Arndt JW, Pena AS, Verspaget HW, Thon A, Tham RTO, Weterman IT, Pauwels EKJ, Lamers CBHW (1988) Value of Indium-i 11 granulocyte scintigraphy in the assessment of Crohn's disease of the small intestine. Digestion 40: 227-236 Feitsma RIJ, Blok D, Wasser MNJM, Nieuwenhuizen W, Pauwels EKJ (1987) A new method for 99mTc-labetling of proteins with an application to clot detection with an antifibrin monoclonal antibody. Nucl Med Commun 8 : 771-777 Fischman AJ, Wilkinson R, Khaw BA, Callahan RJ, Ahmad M, Locke E, Nossiff ND, Strauss HW, Rubin RH (I988a) Imaging of localized bacterial infections with radiolabeled non-specific antibody fragments. J Nucl Med 29:610 (abstr) Fischman AJ, Rubin RH, Khaw BA, Callahan RJ, Wilkinson R, Keech F, Nedelman M, Dragotakes S, Kramer PB, LaMuragia GM, Lind S, Strauss HW (1988 b) Detection of acute inflammation with ~11in_1abeled nonspecific polyclonal IgG. Semin Nucl Med 28 : 335-344 Locher JTh, Seybold K, Andres R, Schubiger PA, Mach JP, Buchegger F (1986) Imaging of inflammatory and infectious lesions after injection of radioiodinated monoclonal anti-granuIocytes antibodies. Nucl Med Commun 7:659-670 Peters AM, Osman S, Henderson BL, Kelly JD, Danpure H J, Hawker R J, Hodgson H J, Neirinckx RD, Lavender JP (1986) Clinical experience with 99~Tc-hexamethylpropyleneamineoxime for labelling leucocytes and imaging inflammation. Lancet ii : 946-949 Roddie ME, Peters AM, Danpure H J, Osman S, Henderson BL, Lavender PJ, Carroll M J, Neirinckx RD, Kelly JD (1988) Inflamation : imaging with 99mTc-HMPAO-labeled leucocytes. Radiology 166:767-772 Rubin RH, Young LS, Hansen WP, Nedehnan M, Wilkinson R, Nelles M J, Callahan R, Khaw BA, Strauss HW (I988) Specific and nonspecific imaging of localized Fischer immunotype 1 Pseudomonas aeruginosa infection with radiolabeled monoclonal antibody. J Nucl Med 29:651-656 Vorne M, Karhunen K, Lantto T, Mokka R, Mfikelfi P, Nikoskelainen J, Rajamfiki A (1988) Comparison of x23I monoclonal granulocyte antibody and 99~Tc-HMPAO-labelled leucocytes in the detection of inflammation. Nucl Med Commun 9 : 623-629
