Successful and unsuccessful approaches to imaging carcinoids: Comparison of a radiolabelled tryptophan hydroxylase inhibitor with a tracer of biogenic amine uptake and storage, and a somatostatin analogue

Abstract

A mouse mastocytoma model was used to determine the biodistribution and tumour uptake of four radiopharmaceuticals developed to target the serotonin synthetic pathway in carcinoid tumours. Three of the compounds were competitive inhibitors of the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. Radiolabelled iodo- dl -phenylalanine (iodine-131 PIPA) was found to have the highest uptake and tumourto-liver ratio. Four patients with known carcinoid tumours were then injected with 0.5 mCi 131 I-PIPA and imaged at 1, 4, 24 and 48 h post-injection. The radiopharmaceutical, however, failed to localize in the known tumour sites. This result was in contrast to the authors' experience of 131 I- and 123 I-MIBG imaging of carcinoid tumours. Seven patients with known metastatic carcinoid tumours, two patients with symptoms of recurrence following tumour resection, one patient with completely resected disease, and two patients with a flushing syndrome of uncertain aetiology were studied with 131 I-MIBG. Three of the seven patients with known metastatic disease had positive 131 I-MIBG scans. Both patients with clinical evidence of recurrent disease had negative scans, as did the patient who was considered to have had complete resection of her primary tumour. The two patients with idiopathic flushing syndrome also had negative scans. Among seven patients imaged with 123 I-MIBG there were four true-negative scans and one falsenegative, the latter in a patient with biochemical and CT evidence of recurrence. In a seventh patient with distant metastases there was variable uptake in some of the lesions. Four patients were studied with indium-111 penetetreodide. Two patients with metastatic carcinoid disease had positive scans, although hepatic metastases were not seen in one. Another two with idiopathic flushing syndrome had normal studies. The literature suggests that up 50% of carcinoid tumour cases are detected with 131 I-MIBG, compared to a sensitivity of 87% reported with somatostatin receptor imaging using 111 In-pentetreotide. The experience with 123 I-MIBG is much less extensive. The mechanisms of carcinoid tumour localization for each of the three classes of radiotracers are discussed and contrasted to their varying sensitivities. The relative success of 131 I-MIBG and 111 In-pentetreotide relative to 131 I-PIPA may be related to the fact that 131 I-MIBG is actively taken up and stored by the enterochromaffin cells of the tumours and 111 In-pentetreotide binds to cell surface receptors, whereas 131 I-PIPA binds to tryptophan hydroxylase, which may be present in quantities too small to permit tumours to be imaged.