FROM THE RADIOTHERAPEUTIC CLINIC, UNIVERSITY O F HELSINKI AND FROM THE SECOND

DEPARTMENT O F HESPERIA HOSPITAL, HELSINKI, FINLAND

EXPERIENCES ON RADIOISOTOPIC DIAGNOSIS O F BRAIN TUMOURS

M. Brenner, T. Pihkanen and A. Voutilainen

At t,he Radiotherapy Clinic of the Helsinki University Central Hospital, in cooperation with the Second Department of the Hesperia Hospital, Hel- sinki, and the Clinic for Neurosurgery of the University of Helsinki, a total of 138 patients was examined by gamma-ray encephalography and 156 scintigrams were taken since the beginning of 1963.

METHODS AND RESULTS Thc equipment used in the examinations was Nuclear Chicago Model 1700 with photo-

graphic recording. At the first experimental stage, I131-labelled human serum albumin was employed

at dosages of 300-400 microcuries. This method has been applied successfully (Di Chiro 1960, Pluniol & Guuthier 1962). Measurements were made 24 hours, after intravenous injection, of 27 patients (Table 1). It can be seen that positive findings were obtained in all nine cases which were verified by pathologic-anatomical examination as neo- plasms, and in a total of 17 cases. The result was negative in ten cases involving suspicion of tumour or tumour metastasis on the strength of clinical findings or findings made a t ncuroradiological examination.

While yielding satisfactory results, this time-consuming method was so cumbersome that i t was abandonned in favour of the HgZu3-neohydrin method, which has been tried out by many authors with rather good success. (Blau & Bender 1959, 1962, Brinkrnan et al. 1961, Croll, Brady & Hand 1962, Dugger & Pepper 1963, Selverstone & Gillespie 1963, Sklaroff et al. 1953).

Intravenous injections were administered consisting of a 600 - 700 microcurie dosis of Hg203-labelled neohydrin, which finds its way to the cerebral tumour within five hours. This method was subsequently employed, Table 2 showing the results of examination obtained in 111 cases. It is seen that in addition to neoplasms other diagnostic categories have also been included in the series, partly in order to serve as controls of the method. In positive, pathologic-anatomically verified tumour cases this isotopic method yielded positive findings in 33 out of 36 cases, equivalent to 92 per cent, while the findings was negative in three of 12 cases in which diagnosis of tumour was likely on the strength of other results of examination. The diagnostic efficiency was thus 75 per cent in this second group. These results are consistent with those reported by, i.a. Duggers & Pepper (1963).

Probable metastases, which were present in 27 cases, could be elicited in 18 instances by this method, corresponding to 67 per cent.

It can be seen that Hgaua-neohydrin encephalography did not produce false positive findings in other disease groups except in a mere three cases of intracranial haemorrhage, which amounts to 3 per cent of the entire series.

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m o ,

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m ( 0 n w a u w w

n m a a m a i m m i

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a) carotid-angiogram b) gamma-encephalogram with HgZo3 Fig. 1. Investigation of patient with cerebral metastasis from bronchial cancer.

If the efficiency of the method is compared to that of the ordinary explor- atory studies undertaken in the present work, the fact has to be kept in mind that pneumo-encephalography in particular was carried out on part of the patients only. On the other hand this reflects the circumstance that expressly pneumographic interference was either contraindicated in certain cases or difficult to perform. This implies that under special conditions prac- tical limitations exist for application of said expedients.

The findings elicited by the mercury method were clear as a rule, and rather sharply circumscribed. This is also true for the demonstration of highly likely cerebral metastases. of which a couple may be presented as examples. The first case (Fig. 1) concerns metastasis of a pulmonary carcinoma, also demonstrated by angiography, while in the other (Fig. 2) there were seminoma metastases in both frontal lobes. which were verified a t autopsy.

In five cases with suspected intracranial metastases this could be verified at autopsy. The diagnosis was made in two of them by gamma-ray encephalo- graphy, whereas the result of scanning was negative in the other three cases. At autopsy, small metastases about y2 to 1 cm in diameter were found in two of the latter; in the third case the metastasis had infratentorial location.

According to the studies of Planiol & Gauthier (1962), infratentorial tu- mours are revealed by isotopic encephalography in 15-60 per cent. In the present series we were able to demonstrate with mercury two tumours having such location.

In the present series the group of non-verified intracranial metastases can be considered virtually to belong to the controls.

Isotopic mapping was undertaken in this group because the patients began, during progress of radiotherapy (for some extracranial tumour), to complain of subjective sumptoms such as nausea, vomiting, fatigue, etc. without pre-

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a) frontal projection b) lateral projection Fig. 2 . Gamma-encephalogram in a patient with cerebral metastasis from a seminoma.

senting any neurological, objective signs of intracranial tumour. The result of isotopic encephalometry was negative in all these 18 cases.

In some of the histologically verified cases the uptake was less strong and the boundaries were blurred. In Table 3 a distinction has been made between powerful, well-circumscribed uptake (f +) and less strong, less sharply de- marcated uptake (+) in the various histological groups. In the majority of the cases deposition of both iodine and mercury clearly occurred, and no negative findings were recorded in any of the cases with astrocytoma or glioblastoma. Two cases of glioblastoma in which the uptake shows to some extent scarply defined boundaries may be presented as examples (Fig. 3 and 4). The uptake was in our material poorest in the oligodendroglioma cases.

TABLE 3. Uptake of the isotope by different types of tumours in 39 patients.

Types of tumour

iistrocytoma Glioblastoma Oligodendroglioma Spongioblastoma Meningeoma Ependymoma Adenoma

Tota

Strong uptake

f i

1 3 6 4 0 0 1 0 '

21

Less strong uptake f

5 1 3 1 1 0 1

No demonstrablt uptake -

12 I 3

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a) gamma-encephalogram b) carotid-angiogram

Fig. 3. Patient with glioblastoma multiforme.

a) lateral projection b) frontal projection

Fig. 4 . Gamma-encephalogram in a patient with glioblastoma multiforme.

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DISCUSSION

Uptake (Remaining activity

per kidney)

1 micro C

It is well-known that the histological structure of the tumour is not alone decisive as regards the result, which is dependent also on the localisation, among other factors. Since the isotopic uptake is abundant in the vicinity of the base of the skull even normally, owing to the large blood vessels, tumour- induced uptake in this region is frequently hard to demonstrate. The technical possibilities existing for achievement of better results cannot be discussed.

Altogether 15 of the present patients were subjected to examination by scanning two or three times, a t varying intervals. The purpose was to ob- serve any changes that might take place in the tumour after radiotherapy and to compare the results with the clinical findings. The control examina- tions revealed reduced uptake in eight patients, whose clinical picture had developed in a favourable direction a t the same time. Neoplastic progression was noted in four cases. In the other cases the status remained unchanged.

In focal epilepsy, cerebrovascular diseases, and thromboses the findings at scanning were invariably negative. On the other hand a positive finding was recorded in three out of four cases of intracranial haemorrhage. One of these cases was verified a t autopsy and another a t operation. In the first-mentioned a fresh haemorrhage was concerned and in the other an inveterate haema- toma capsule with increased isotope uptake.

Part of the Hg-neohydrin is deposited in the kidneys, but no risk of ra- diation damage is thought to be involved. According to the American authors Dugger and Pepper, 700 microcuries produce in the kidneys a radiation dosis of about 40 rad. In our studies the renal HgZo3-neohydrin activity was measured in three patients and post mortem in one further case. Table 4 reveals that the mean dosis present in the kidneys was 38 rad. There was a somewhat higher intensity of beta than gamma radiation, and the effective half-life was 25 days on the average. The radiation dosis received by the en- tire body has been measured a t 290 millirad by the said Americans.

TABLE 4. The renal uptake of the isotope Hqzo3- neohydrin.

Renal dose

Rad Remarks

Beta I Gainma I Total

isotope Patient

2 . s 20 22 13 35 4.0 28 14 8 22 7.1 50 30 17 56 4.4 31 26 14 39

1 indays

in vivo in vivo in vivo

post mortem

RI TJ IH

Mean Value 1 25

35 16 23

4.6 I 32 I I I 38 I

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CONCLUSIONS Isotopic encephalography justifies its place as an aid in the localizing of

cerebral tumours and in determination of their size. However, it cannot be considered superior to the x-ray examining methods in present use, since it has been found that frequently certain regions cannot be assessed with its aid, such as the infratentorial area and the base of the skull, as well as areas close to the median line. But the method has a number of advantages, of which the following may be mentioned:

(1) The examination is completely painless, in all likelihood free of risk, hardly constituting any stress on the patient, and it can be performed on ambulatory patients in five hours if e.g. HgZo3-neohydrin is used. It may be recommended also for patients in poor condition even as the first expedient in examination.

( 2 ) The examination may be indicated, e.g. prior to commencement of radiotherapy, because in most instances the position and to some extent the size of the tumour can be assessed with its aid and the treatment planned accordingly.

(3) The examination is also recommended as a method of follow-up study. It often provides a possibility to demonstrate either progression or regression of the tumour. (4) Demonstration of potential cerebral metastases in connection with the

treatment of primary tumours is in many cases successful by the scanning method, although the limitations of the method have to be taken into account.

It is to be expected that further rapid development will take place in gam- ma-ray encephalography in the immediate future.

SUMMARY Preliminary experiences of gamma-encephalography in 138 patients are

reported. In 27 cases human serum albumin labelled with radioactive iodine and in 111 cases neohydrin labelled with radioactive mercury were used. The latter was found to be more practical and less time-consuming. This Hg203-method gave a positive result in the group of pathologic-anatomically verified tumour cases in 27 out of 30, equivalent to 90 per cent. In the patient group of probable intracranial metastasis the diagnostic efficiency was found to be 67 per cent.

False positive findings were not found except for three instances of intra- cerebral haemorrhage. The poorest uptake was ' observed by oligodendro- gliomas showing false negative results in 3 cases out of 4.

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The renal uptake of HgZo3-neohydrin was measured intravitally in three patients and post mortem in another case.

It is concluded that isotopic encephalography justifies its place as an aid in the diagnostics of intracranial tumour. The method can be regarded t o have certain advantages. First of all it is painless, without contraindications, may be applied to ambulatory patients.

REFERENCES Blau, M., & M . A . Bender (1959): Radiomercury (HgZoa) labelled Neohydrin: A new agent

for brain tumor localisation. J.Nucl.l\led.Convention Issue 35- 42. Blau, M., & M . A. Bender (1962): Radiomercury (Hg20S) labeled Neohydrin: A new agent

of brain tumor localisation. J.Nucl.Med. 3, 83-94. Brinkman, C . A . , A . V. Wegst, T . P. Huynie, & C. E. Nasjleti (1961): Localization of

intracranial tumors utilizing HgZo3 labeled Neohydrin and the photoscanner. Univ.Med.Bul1. 27, 221 -224.

Croll, M . N . , L. W . Brudy, & B. M . Hand (1962): Brain tumor localization utilizing mer- cury-203. Radiology 78, 635-637.

D i Chiro, G. (1960): Risa encephalography and conventional neuroradiological methods. Acta Radiol. Supplem. 201.

Dugger, G. S., & P. D., Pepper (1963): The realibility of radioisotopic encephalography. Neurology 13, 1042- 1053.

Planiol, P. Th., & G. Guuthier (1962): Gammaencephalographie. Szintigraphie und radio- kardiographie. Base1 33-52.

Selverstone, B., & G. G. Gillespie (1963): Localization of brain tumors with radioactive mercury. Tufts fol.Med. 9, 77-82.

Skluroff, D., P. P. Polakoff, P. M. Lin, & iV. D. Charkes (1963): Cerehral scanning with radioactive chlormerodrin (Neohydrin). Neurology 13. 79 - 85.

Toivo Pihkanen M. Brenner A. Voutilainen l\led.dr. Fil.dr. Med.dr. Hesperia sjukhus Radiotherapeutiska klin. Radiotherapeutiska klin.

Helsingf ors Finland

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