SUCCESSFUL AND UNSUCCESSFUL APPROACHES TO IMAGING CARCINOIDS - COMPARISON OF A RADIOLABELED TRYPTOPHAN-HYDROXYLASE INHIBITOR WITH A TRACER OF BIOGENIC-AMINE UPTAKE AND STORAGE, AND A SOMATOSTATIN ANALOG

A mouse mastocytoma model was used to determine the biodistribution an d tumour uptake of four radiopharmaceuticals developed to target the s erotonin synthetic pathway in carcinoid tumours, Three of the compound s were competitive inhibitors of the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase, Radiolabelled iodo-DL-phenylalanin e (iodine-131 PIPA) was found to have the highest uptake and tumour-to -liver ratio, Four patients with known carcinoid tumours were then inj ected with 0.5 mCi I-131-PIPA and imaged at 1, 4, 24 and 48 h post-inj ection. The radiopharmaceutical, however, failed to localize in the kn own tumour sites. This result was in contrast to the authors' experien ce of I-131- and I-123-MIBG imaging of carcinoid tumours. Seven patien ts 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 uncert ain aetiology were studied with I-131- MIBG, Three of the seven patien ts with known metastatic disease had positive I-131-MIBG scans. Both p atients 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 pa patients with idiopathic flushing s yndrome also had negative scans. Among seven patients imaged with I-12 3- MIBG there were four true-negative scans and one false-negative, th e 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 pe netetreodide. Two patients with metastatic carcinoid disease had posit ive scans, although hepatic metastases were not seen in one, Another t wo with idiopathic flushing syndrome had normal studies, The literatur e suggests that up 50% of carcinoid tumour cases are detected with I-1 31-MIBG, compared to a sensitivity of 87% reported with somatostatin r eceptor imaging using In-111-pentetreotide. The experience with I-123- MIBG is much less extensive. The mechanisms of carcinoid tumour locali zation for each of the three classes of radiotracers are discussed and contrasted to their varying sensitivities, The relative success of I- 131-MIBG and In-111-pentetreotide relative to I-131-PIPA may be relate d to the fact that I-131-MIBG is actively taken up and stored by the e nterochromaffin cells of the tumours and In-111-pentetreotide binds to cell surface receptors, whereas I-131-PIPA binds to tryptophan hydrox ylase, which may be present in quantities too small to permit tumours to be imaged.