British Journal of Radiology (2004) 77, 525-527
© 2004 British Institute of Radiology
doi: 10.1259/bjr/23668769
Drug interference with MIBG uptake in a patient with metastatic paraganglioma
K Zaplatnikov, MD1,
C Menzel, MD1,
N Döbert, MD1,
N Hamscho, MD1,
W T Kranert, PhD1,
M Gotthard, MD2,
T M Behr, MD2 and
F Grünwald, MD1
1 Department of Nuclear Medicine, Hospital of the J.W. Goethe-University, Frankfurt/Main and 2 Department of Nuclear Medicine, Hospital of the Philipps-University, Marburg, Germany
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Abstract
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Metaiodobenzylguanidine (MIBG) labelled with iodine-131 (131I) has become a well established therapeutic tool for inoperable metastastic tumours of paraganglioma. There are different pharmacological substances known to interfere with MIBG-uptake which may result in a false negative MIBG scan. We present the case of a 26-year-old male polytoxicomanic patient with metastatic paraganglioma, who underwent MIBG therapy. During earlier therapies, MIBG uptake in the metastatic lesions was very high. A post-therapeutic whole-body scan subsequent to recent 131I-MIBG therapy failed to detect the vast majority of metastatic lesions-except for two. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed metastases with a similar distribution to the initial MIBG scan. The possible reasons for the discrepancy in the findings of the MIBG scans and the 18F-FDG-PET scan are discussed with special emphasis on drug intake prior to MIBG administration, increased MIBG turn-over and unknown drug mixture interference with MIBG uptake.
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Case report
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A 26-year-old polytoxicomanic male patient with paraganglioma and metastases of the bones, lungs and lymphatic nodes underwent adrenalectomy and nephrectomy in 1997. The patient had a history of drug consumption—heroine, cocaine, benzodiazepines, amphetamines and alcohol for at least 5 years in varying combinations and intensities in detail unknown to us. There were also phases of drug withdrawals. At the time of presentation in our department, he had already received 7 metaiodobenzylguanidine (MIBG) therapies.
Physical examination and laboratory work was regular except for a borderline anaemia.
In the previous MIBG therapies, the metastatic lesions had revealed a significant MIBG uptake as shown in post therapeutic scintigraphy. Before the recent therapy, the patient was on a methadone substitution program (25 mg/day). In addition, the patient had received thyroid hormones and over 1 month ago mirtazapine (anti-depressant) and metoclopramide. Drug screening was performed regularly.
After application of potassium iodide (0.2 mg per day, beginning 48 h before MIBG and continuing until 2 weeks after therapy) a single dose of 131I-MIBG (5.6 GBq) was administered intravenously. There were no complications from the therapy except a slight fugitive nausea on day 2 after therapy. On the days following, no other drugs were given. On day 13 after initial therapy, whole-body scintigraphy (Siemens Body Scan, Erlangen, Germany; matrix 384 x 1024, HEAP, scan-speed 5 cm min–1) and a 18F-FDG-PET scan (Siemens EXACT47; 5 bed-positions/5 min, 298 MBq 18F-FDG, blood sugar after a 17 h fasting was 84 mg dl–1) were performed.
In contrast to the seventh MIBG whole-body scan (Figure 1a
), the latest MIBG scan failed to detect the vast majority of metastatic lesions, except for two lesions (abdomen and right proximal femur) (Figure 1b). The subsequent FDG-PET scan showed metastases with a glucose metabolism similar in distribution to the initial MIBG scintigraphy (Figure 2).
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Figure 1. (a) In contrast to the previous post-therapeutic 131I-MIBG-whole-body scan, (b) the latest scintigraphy failed to detect the vast majority of metastatic lesions except for two lesions (abdomen and right proximal femur).
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Figure 2. A coronal slice of the FDG-PET scan shows multiple metastases with a similar distribution to the 7th MIBG whole-body scan.
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Discussion
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Malignant paraganglioma is a rare neuroendocrine tumour, which has its origin in the chromaffine cells of the sympathetic and parasympathetic nerve ganglions. The incidence of this disease has been reported as 0.001% to 0.002% [1]. The localization of these tumours is variable (e.g. carotid and jugular medial nerve-bulbus, ganglion of the N. vagus, mid-ear) and metastases occur predominantly in bones and lymph nodes [2]. Metastases and a resulting complicated course of the disease are more often observed in paraganglioma compared with pheochromocytoma (20–25%) [3]. The symptoms of this disease may vary consisting of pain as a result of tumour growth or increased blood pressure caused by catecholamine release. MIBG is a noradrenaline-analogue, which undergoes active transport and is stored in the adrenergic vesicles of chromaffine cells. In the case of high MIBG doses, the uptake mechanisms also involve diffusion. MIBG scintigraphy with 123I is a well-established diagnostic method with high sensitivity and specificity (MIBG uptake in more than 90% of all paraganglioma), which can also be used for therapy control [4, 5]. In MIBG-positive inoperable paraganglioma, the use of 131I -MIBG is the therapy of first choice. After 131I-MIBG therapy, tumour reduction, hormone-suppression or symptomatic benefits can be observed in approximately 70% of patients with metastatic malignant paraganglioma or pheochromocytoma [6–8].
There are several pharmacological substances known to interfere with the MIBG uptake, e.g. recreational drugs (cocaine, derivatives of ephedrine) inhibiting the sodium dependent uptake mechanism. These and other substances are listed in detail in the publications of Solanki [9] and Wafelman [10]. To avoid therapeutic ineffectiveness, substances which may interfere with MIBG uptake have to be discontinued at least 1 to 3 weeks in advance of treatment, depending on the pharmacological kinetics of the substance used.
In the present case, all previous scans after MIBG therapies had shown high MIBG uptake in the metastatic lesions of the paraganglioma. However, the last whole-body scan revealed an almost complete blockage of MIBG uptake, although the FDG-PET scan showed an unchanged glucose metabolism in the known metastatic lesions.
The reason for this phenomenon is unclear. The course of therapy and the external parameters such as dose, medication before and after the therapy, methadone-substitution, were identical to the previous MIBG therapy. In addition, the time-period between MIBG administration and post-therapeutic whole-body scintigraphy (13 days) may be excluded as a factor which interfered with the result, because the trapping effect can cause increased uptake. The remaining activity of the therapeutic dose also does not explain the lack of MIBG uptake. Dedifferentiation of the tumour tissue or an increased MIBG turn-over in the metastatic lesions may be possible explanations [7], although a general dedifferentiation of all tumour tissue is highly unlikely. In addition, the 18F-FDG-PET scan did not reveal differences in the glucose metabolism of the metastatic lesions, which would be expected in the event of histological dedifferentiation of the tumour tissue.
Therefore, the most likely cause of this "false scan" is the rapid interference of recreational drugs with the MIBG uptake (e.g. cocaine, ephedrine etc.) which were unfortunately probably taken just before this MIBG therapy. In previous MIBG therapies, a good MIBG uptake had been observed in this patient. This was most likely because he had been either withdrawing from drugs, or during this stage was consuming heroine which was not interfering with MIBG uptake.
Another reason may be an unknown drug mixture, causing a long lasting blockage of the MIBG uptake. This theory is based on the decreased uptake of 131I-MIBG into the salivary gland in comparison with the previous examination (Figure 1
). The salivary gland uptake has been proposed to indicate a possible drug interference phenomenon [11].
The patient in this report showed very poor compliance caused by further deterioration of his drug habits, so that planned additional diagnostic and post-therapeutic procedures have not yet been implemented.
This work concludes that in patients with a history of drug abuse it is advisable to take a thorough drug history, to perform pre-therapeutic drug screening and if necessary to repeat MIBG scintigraphy in the event of a negative outcome.
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Footnotes
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Address correspondence to Konstantin Zaplatnikov, Department of Nuclear Medicine, Hospital of the J.W.Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany. 
Received for publication April 4, 2003.
Revision received July 24, 2003.
Accepted for publication September 30, 2003.
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References
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Abstract
Case report
