European Journal of N u c l e a r

Eur. J. Nucl. Med. 2, 8 9 - 9 2 (1977)

Medicine

© by" Springer-Verlag 1977

Comparative Study of 111in and S9Fe Bone Marrow Scanning C. Parmentier, F. Therain, P. Charbord, B. Aubert, and N. Morardet* Unit+ de M+decine Nucl+aire, Institut Gustave-Roussy, 16 bis avenue Paul-Vaillant-Couturier, F-94800 Villejuif, France

Abstract. The aim of this work is to examine the

relative merits of S9Fe and l~aIn scanning in estimating the functional value of the various erythropoietic areas and in appraising bone marrow distribution and extension. At first we studied a group of patients with heterogeneous distribution of bone marrow secondary to irradiation, ferrokinetics serving as reference for the comparison of 1~~In and 59Fe scanning. The functional value of S9Fe scanning was thus proved, in contrast to ~ttin scanning which was erroneous for 13 of the 29 bone marrow areas studied. A further study of patients presenting polycythemia vera or anemia with l ~ I n demonstrated in some cases false distribution and bone marrow extension. Furthermore, 59Fe scanning permitted evaluation of the efficiency of erythropoiesis and the existence of extramedullary erythropoiesis. Review of the literature revealed that with the activity used there was no dosimetric advantage of ~ 1In over 59Fe.

Introduction

The aim of this study is to compare the respective value of 59Fe and ~11In transferrin in evaluating bone marrow distribution and extension. In addition to ferrokinetics, S2Fe [1] was used at first to study bone marrow distribution. But this cyclotron radionuclide is not available to most departments of nuclear medicine; its detection is effected under good conditions by means of a positron camera; scanning carried out several hours after the injection requires very high activities, which limits the dosimetric interest of this short-period radionuclide. Due to its high energy and long period, 59Fe is difficult * Attach6e de Recherches I N S E R M Offprint requests should be sent to Prof. C. Parmentier

to use. However, as early as 1969 Ronai et al. [12] refer to its utilization, but prefer SZFe. Recently Chaudhuri emphasized the results obtained with 59Fe ' and proposed an appropriate collimated detector [4]. Furthermore, as early as 1973 several studies [6, 10] showed the value of 111In transferrin in bone marrow scanning.

Material and Methods 1. Material. 59Fe citrate was incubated with the patients' plasma, after verifying the transferrin saturation; the activity injected was that usually used for ferrokinetics (15 to 20 ~tCi). 111In chloride (Philips Duphar) was incubated with purified transferrin (Centre National de transfusion sanguine de Paris) in a highly acid solution (HC1 0.04N); the activity injected ranged from 1.5 to 2.5 mCi. The SgFe and 111In scanning was carried out on a whole body Ohio Nuclear scanner type 84 D with two heads, each equipped with a crystal 125 m m in diameter and 50 m m thick. The H~In scannings were performed on the photoelectric peak at 247 keV and with the collimator 38 M adapted to this energy. For the 59Fe scan we had to design a collimator adapted to high energy photoelectric peaks: 1098 keV and 1289 keV. The crystal size and the thickness of the lead required to obtain an appreciable reduction (3,3 cm for 1/10 reduction) compelled us to design a collimator with only one hole. This hole has a converging conical shape with the following characteristics:

Input pupil radius Output pupil radius Height Focal distance

18 m m 38 m m 115 m m 103.5 m m

The collimator was tested by measuring the line spread functions (LSF). For this purpose we moved a radioactive line of S9Fe 250 m m long in front of the collimator and at distances from the collimator ranging from 25 m m to 200 mm. Figure 1 shows the characteristics resulting from the LSF. Figure l a shows the resolution index variation (full width at half m a x i m u m of LSF) in relation to the distance from the source to the collimator. Figure I b shows the relative efficiency variation ( m a x i m u m value of LSF) in relation to the distance from the source to the collimator (100% at 25 mm).

90

C. Parmentier et al. : Comparative Study of ~HIn and 59Fe Bone Marrow Scanning Table 1. Collimator comparison

150-

E E

Collimator

1t 1in

59Fe

Plane sensitivity 57Co cpm/(pCi/cm 2)

39,200

261,000

Geometrical plane source efficiency (cm 2)

24- 10 3

278- 10- 3

10o-

x

50-

2 o

[a}

"" "'" . . . . .

J'~"

COL1111n

n~

5~

11~0 Depth (mm]

1~0

200 Table 2. Technical settings for 11l in and 59Fe imaging

100~%~\

04

75-

\\\\ 50-

Fe

._u LLI

\,

25"

38M~ COL.111In

(b)

0

1;0

4o

2;0

Depth ( m m )

Radioisotope

111In

59Fe

Baseline (keV)

200

Window (keV) Maximum counting rate (cpm) Minification of the film Line spacing (ram) Scanning speed (mm/min) Slit light shaper Enhancement (%) Background (%) Intensity setting Scan time (rain)

80 30,000 5:1 6.25 3,800 middle 0 5 20-25 50-60

960 (480 graduations)a 220 2,0004,000 5: 1 12.5 2,300 large 0 5 15-50 3040

a For 59Fe, the value of high-voltage power supply is adjusted to give a correspondence between the 137Cs photopeak (662 keV) and the graduation 331

Fig. 1. a Resolution index (FWHM) versus distance collimator to line source, b Efficiency versus distance collimator to line

3. Method of Comparison. Ferrokinetics including surface counting for 2 weeks, 59Fe scanning at day 1 and 7, and 11~In scanning 48 h after an injection of In transferrin made on the last day of the iron test, were systematically performed for each patient. As other authors [8, 10, 11], we found 48 h to be the best delay for 11~In scans. For 59Fe external surface counting, the norm for the maximum bone marrow activity, corrected for circulating activity, was previously determined [9]. The 1~ I n and 24th-hour 59Fe scannings were analyzed according to a semiquantitative and double-blind method. The degree of fixation in bone marrow segments was classified using 4 grades, from 0 to + + + . For patients with hematosarcoma two or three not irradiated

By way of comparison the characteristics of the collimator 38 M response are shown as a dotted line in front of a linear source of HaIn. We also measured the sensitivity of both collimators in front of a plane source of STCo and calculated the geometric efficiency [3]. The results are shown in Table 1. The various adjustments and parameters relative to the 59Fe and ~ a l n tests are grouped together in Table 2.

2. Patients. We studied 6 patients with hematosarcoma in complete remission 2 to 9 years after large target volume irradiation. We next studied 19 other patients with either polycythemia vera or anemia due to a production disorder.

Table 3. Comparison of 59Fe and 111In scannings with 59Fe external countings for 6 patients with an hematosarcoma previously treated by large target volume irradiation Areas of references

Irradiated areas

Number of points of references

18

Type of scanning

Comparison of scintigraphic Grades with the maximum of 59Fe external counting

Nonirradiated areas

lilIn

11 59Fe

iliIn

59Fe

overestimation underestimation

4 2

0 0

0 3

0 0

nonvisualization agreement

4 8

0 18

0 8

0 11

10

0

3

0

Number of patients with discrepancy

C. Parmentier et al. : Comparative Study of 11~in and 59Fe Bone Marrow Scanning

91

and three irradiated bone marrow areas were chosen; in each area 59Fe and ~ t l n scintigraphic grades were compared to the value of the maximal 59Fe external counting; it was thus possible to study 29 areas. For the other patients with anemia or polycythemia vera, a comparison of the SgFe and 11~In scintigraphic grades was made.

Results

1. Normal Aspect of 59Fe and lllIn Scanning Normal Aspect of 59Fe Scanning. D e s p i t e b a d resolution, well c o n t r a s t e d images are o b t a i n e d at d a y 1 because o f very low b a c k g r o u n d . Sacrum, d o r s o l u m b a r rachis ( p o s t e r i o r incidence), pelvis, a n d s t e r n u m ( a n t e r i o r incidence) a r e clearly visualized. 7 days after injection: f i x a t i o n a r e a s on the 1st d a y are no longer a p p a r e n t ; c a r d i a c a r e a a n d m a j o r b l o o d vessels are apparent.

Normal Aspect of 111In Scanning. The r e s o l u t i o n is better, the b o n e c o n t o u r s are clear-cut. A h e p a t o s p l e nic i m a g e is a l w a y s a p p a r e n t : on the p o s t e r i o r incidence for the spleen, on b o t h incidence for the liver. C u t a n e o m u s c u l a r a n d b l a d d e r activity is variable.

2. Study in Patients with Hematosarcoma T h e results a r e s h o w n in T a b l e 3. A n excellent correlat i o n was o b s e r v e d b e t w e e n the 59Fe external surface c o u n t i n g a n d 59Fe s c i n t i g r a p h i c g r a d e s in the 29 areas selected; a c o r r e l a t i o n with 1~1in scintigraphic grades was only a p p a r e n t in 8 o u t o f 18 i r r a d i a t e d areas a n d 8 o u t o f 11 n o n i r r a d i a t e d areas. In addition, femoral and/or humeral bone marrow extension was f o u n d by b o t h r a d i o n u c l i d e s in three p a t i e n t s : i n the 59Fe s c a n n i n g o n l y on the e p i p h y s e s ; in the ~11In s c a n n i n g on the d i a p h y s e s as well in two o u t o f f o u r extensions.

3. Study in Patients with Anemia or Polycythemia Vera I n three cases the l l l I n d i s t r i b u t i o n d i d n o t corres p o n d to the e r y t h r o p o i e t i c m a r r o w d i s t r i b u t i o n : und e r e s t i m a t i o n o f d o r s a l e r y t h r o p o i e s i s in a case o f c h r o n i c t h o r o t r a s t i r r a d i a t i o n , u n d e r e s t i m a t i o n o f sacral e r y t h r o p o i e s i s in a p r e l e u k e m i e state, a n d overest i m a t i o n o f all the e r y t h r o p o i e t i c b o n e m a r r o w in a case o f myelofibrosis. D i s t a l m a r r o w extension was u n d e r e s t i m a t e d by 11 ~In in three cases o u t o f eight (Fig. 2 a) Conversely, in two cases b o n e m a r r o w extension was suggested in 1 1 q n scanning whereas it was r u l e d o u t in the 59Fe s c a n n i n g (Fig. 2 b )

Fig. 2. a Patient in aplasia with a lymphosarcoma treated by chemotherapy and radiotherapy. The 59Fe posterior scans (1 and 7 days after injection) show that femoral bone marrow extension is the unique efficient erythropoiesis area; this extension is underestimated with 11~In scan. b Patient with anemia. The 1~lin posterior scan shows a bone marrow extension not seen on the 59Fe scan (1 day after injection)

In all the cases, i n d e p e n d e n t o f the i r o n test results, the liver a n d spleen are visible on the I n d o c u m e n t . Discussion T h e 59Fe test gives a precise a n d q u a n t i f i e d e v a l u a t i o n o f the e r y t r o p o i e s i s o f a given b o n e m a r r o w area.

92

C. Parmentier et al. : Comparative Study of ~11In and 59Fe Bone Marrow Scanning

Table4. Absorbed radiation dose to main organs after labeled transferrin injection [5, 6] Type of labeling

Bone marrow Blood Liver

11~In

SgFe

Dose

Mean dose by scanning (rad/mCi) (rad)

Dose

3.6 0.5 4.5

140 77 150

7 1 9

Mean dose by scanning (rad/mCi) (tad) 2 1 2.5

erythropoiesis and of erythropoiesis efficiency by means of repeated scanning. Moreover, it appears that the doses delivered to the principal target organs for 59Fe are not higher with the activity we administered than those given by 11tin transferrin (Table 4, [5, 6]). The use of an interface will make it possible to improve resolution in 59Fe scanning and to quantify the activity of each erythropoietic area.

References

10].

1. Anger, H.O., Van Dyke, D. : Human bone marrow distribution shown in vivo by iron-52 and the positron scintillation camera. Science 144, 1587 1589 (1964) 2. Beamish, M.R., Brown, E.B.: A comparison of the behavior of 11l in and 59Fe-labeled transferrin on incubation with human and rat reticulocytes. Blood, 43, 703-711 (1974) 3. Beck, R.N.: Collimation of gamma rays. In: Fundamental problems in scanning. Gottschalk, A. and Beck, R.N. Ed. Springfield: Charles C. Thomas 1968 4. Chaudhuri, T.K., Ehrhardt, J.C., Degowin, R.L., Christie, J.H. : 59Fe whole-body scanning. L Nucl. Med. 15, 667-673 (1974) 5. Hine, G.J., Hohnston, R.E.: Absorbed dose from radionuclides. J. Nucl. Med. 11,468 469 (1970) 6. Lilien, D.L., Berger, H.G., Anderson, D.P., Bennett, L.R.: 111In chloride: a new agent for bone marrow imaging. J. Nucl. Med. 14, t84-186 (1973) 7. Mac Intyre, P., Larson, S.M., Eiknan, E.A., Colman, M., Scheffel, U., Hudkinson, B. : Comparison of the metabolism of iron-labeled transferrin (Fe-TF) and indium-labeled transferrin (In-TF) by the erythropoietic marrow. J. Nucl. Med. 15, 856 862 (1974) 8. McNeil, B.J., Holman, B.L., Button, L.N., Rosenthal, D.S.: Use of indium chloride scintigraphy in patients with myelofibrosis. J. Nucl. Med. 15, 647-651 (1974) 9. Morardet, N., Parmentier, C., Flamant, R. : Etude par le Fer 59 des effets de la radiothbrapie ~tendue des h6matosarcomes sur l'6rythropo'i6se. Biomedicine 18, 228-234 (1973) 10. Rain, J.D., Eberlin, A., Boulard, M., Dresch, C., Najean, Y.: Scintigraphie de la mo~lle osseuse. I. Etude exp~rimentate du marquage m~dullaire par l'Indium. R6sultats pr~liminaires obtenus chez l'homme. Nouv. Rev. Fr. Hematol. 13, 78%801 (1973) 11. Rayudu, G.V.S., Shirazi, S.P.H., Fordham, F.W, Friekman, A.M. : Comparison of the use of s 2Fe and ~~1in for hemopoietic marrow scanning. Int. J. Appl. Radiat. Isot. 24, 451-454 (1973) 12. Ronai, P., Winchel, H.S., Anger, H.O., Lawrence, J.H. : Wholebody scanning of S9Fe for evaluating body distribution of erythropoietic marrow, splenic sequestration of red cells and hepatic deposition of iron. J. Nucl. Med. 10, 469 474 (1969)

In conclusion, 59Fe scanning seems to be more reliable. It furnishes data that ~1~In scanning cannot provide, by permitting evaluation of extramedullary

Received October 25, 1976

But the study of the erythropoietic bone marrow distribution is limited with this method. Under these conditions, in order to evaluate the functional value of two types of scanning proposed for the study of erythropoiesis, SgFe and 111In scanning, surface counting on a certain number of bone marrow segments served as a reference. In six patients with heterogeneity of the hematopoietic bone marrow due to a previous irradiation for hematosarcoma, on all bone marrow segments selected a perfect correlation was found between the semiquantitative evaluation of 59Fe fixation in 59Fe scanning at day 1, and the value of the maximum of 59Fe external surface counting; in contrast, the semiquantitative evaluation of fixation in 111In scanning was erroneous in 13 out of 29 segments studied. In view of these first results in 19 patients with anemia or polycythemia vera, the 59Fe scanning. served as a reference to the evaluation of the erythropoietic bone marrow by 11tin scanning. In l0 patients the 11~In distribution did not correspond to the erythropoietic bone marrow. The discrepancies not only involved normal erythropoietic areas but also distal extension areas. They were observed in cases of anemia as well as polycythemia vera. The conditions for the tests being optimal, the discrepancies observed appear to be related to metabolic differences between the two radionuclides clearly demonstrated by experimental works [2, 7,