Eur J Nucl Med (1988) 13:574-577 Eurooean N u c l e a r Journal of Medicine © Springer-Verlag1988 The biodistribution and pharmacokinetics of meta-iodobenzylguanidine in childhood neuroblastoma L.S. Lashford 1' 2, j. Moyes 3, R. Ott 3, S. Fielding 3, j. Babich 3, S. Mellors 3, I. Gordon 2, K. Evans 2 and J.T. Kemshead t 1 ICRF Oncology Laboratory, Institute of Child Health, 30 Guilford Street, London WCINIEH, UK 2 The Hospital for Sick Children, London, UK 3 The Royal Marsden Hospital, Sutton, Surrey, UK Abstract. MIBG is generating considerable interest for the treatment of neuroblastoma. This study has investigated the biological variation in handling of the compound in children with neuroblastoma. The biodistribution of the compound has been characterised in children undergoing tracer administrations of ~23I and t31I-mIBG. Estimates of hepatic and whole body radiation dose delivery have been made. The results indicate substantial interpatient variation in hepatic dose delivery. This organ may be criti- cal in some patients undergoing targeted radiotherapy with mIBG. Key words: MIBG - Neuroblastoma - Dosimetry - Phar- macokinetics - Biodistribution The sympathetic ganglion blocker guanethidine relies for its therapeutic effect on the ability to concentrate in neu- rosecretory granules. Analogues of guanethidine have been synthesised which share this property, and are also easily radiolabelled with isotopes of iodine. In particular, the ana- logue meta-Iodobenzyguanidine (mIBG) has found use as a radiotracer for both normal and abnormal tissue derived from the autonomic nervous system. The first tumour to be imaged in this way was phaeochromocytoma where be- nign and malignant tissue has been detected with a high degree of sensitivity and specificity (Shapiro et al. 1985). Sufficient uptake of mIBG into turnouts has been achieved to undertake therapy by targeting ~31I to phaeochromocy- toma (Sisson et al. 1984). Neuroblastoma shares with phaeochromocytoma the ability to actively accumulate mIBG into neurosecretory granules. The use of the compound as a targeting agent in neuroblastoma is attractive for a number of reasons. Firstly, conventional therapy has made little impact on the outcome of stage IV disease (Shafford et al. 1984). Second- ly, the tumour is highly radiosensitive (Deacon et al. 1985). However, disease is often widely disseminated making ap- plication of external beam therapy difficult without sub- stantial systemic toxicity. The use of targeted radiotherapy has the theoretical advantage of high tumour dose delivery with low systemic toxicity. Few model systems are available to study the uptake of mIBG into neuroblastoma cells either in vivo or in vitro. Offprint requests to ." L.S. Lashford The cell line SK-N-SH has been reported to take up mIBG but the origins of this line are controversial. Whilst original- ly classified as a neuroblastoma the line is now believed to be from a patient with a neuroepithelioma (F.F. Proceed- ings 1985). In the absence of adequate models to study mIBG uptake into neuroblastoma, the biodistribution and pharmacokinetics of the compound have been investigated in children with stage III or IV neuroblastoma imaged with mIBG. Materials and methods t3tI-mIBG was purchased from Cis and Mallinckrodt. a23I- mIBG was prepared in the laboratory according to the method of Wieland et al. (1980). Between 1 and 2 mg mIBG were added to 370 MBq 123I supplied in a dried form from Harwell and 100 ~tl glacial acetic acid was added to this mixture followed by 3 5 mg ammonium sulphate powder. The bottle was sealed and heated for 45 min at 140 ° C- 160° C in a glycerol bath after which 1.5 ml 0.005 M acetate buffer was added (pH 4.1) and free iodine removed from the preparation following passage through a Cellex-D ion exchange column. Radiolabelled mIBG was sterilised by passage through a 0.22 gm Millex filter and collected in an evacuated vial. The radiochemical purity of the prepara- tion was determined by thin layer chromotography using a 3:1 mixture of propan-l-ol and 10% ammonium hydrox- ide. Patient studies. Seventeen children with variable tumour burden were entered into the study with informed parental consent and ethical committee approval. To effect thyroid blockade, children received 0.3 ml Lugol's iodine 3 times daily for a period of 72 h before, and 1 week after, injection of radiolabelled mIBG. Each patient received a standard tracer dose ofmIBG, 20 MBq t3tI-mIBG was given to chil- dren, irrespective of body weight (specific activity 74 MBq/ rag). For patients receiving a23I-mIBG, a dose of 10 p.g/kg body weight was administered amounting to between 20 MBq and 185 MBq (specific activity 370 MBq/mg). The early biodistribution of the compound was studied in five patients by a dynamic acquisition series; mIBG was injected intravenously, with the patient lying supine on the camera face. Thirty sequential 1 min views of abdomen and thorax were collected. Static acquisition scans were ob-