Distribution and elimination of the somatostatin analogue (111In-DTPA-D-Phe1)-Octreotide (OctreoScan111).

The distribution and elimination characteristics of the 111In-labelled somatostatin analogue OctreoScan111 were studied in 23 patients with malignant tumours. The substance exhibited a rapid blood elimination following a bi-phasic pattern. The initial part of the elimination curves showed a t1/2a of between 0.27 and 3.6 h. The patients investigated had creatinine clearance rates ranging from 33 to 124 ml/min. However, within this range, no apparent correlation was found between the OctreoScan111 elimination rate and kidney function. Also no correlation was observed between the amount of administered activity and the elimination rate of OctreoScan111. The serum radioactivity of 6 patients was analyzed with respect to molecular size. These experiments showed that OctreoScan111 circulated unbound in serum. About 3% of the radioactivity, most probably representing 111In-chloride of DTPA-111In-chloride, circulated protein-bound. The elimination of OctreoScan111 radioactivity in urine displayed a bi-phasic pattern. Size separation of the radioactivity appearing in the urine after 24 h showed a higher molecular weight when compared with OctreoScan111, indicating the existence of a metabolite of the injected substance. The results obtained are discussed in the light of a potential role for the substance in systemic radiotherapy.

Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors.

Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who received the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.

Recombinant interferon alpha-2b in patients with metastatic apudomas: effect on tumours and tumour markers.

Malignant carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid are tumours with similar clinical features. In patients with unresectable or metastatic tumours leukocyte interferon (IFN) and recombinant human (rh) IFN have demonstrated efficacy. Twenty-four evaluable patients with progressive tumours were treated with 2.5 megaunits rh IFN alpha-2b, administered once daily subcutaneously, for a median duration of 7 months (range 0.5-37+). Two carcinoid patients demonstrated a response in tumour size, 80% showed stable disease (SD). Sixty percent of the carcinoid patients with elevated urinary 5-hydroxyindoleacetic (5-HIAA) levels reached a biochemical partial response of the urinary 5-HIAA levels (median duration 13.5 months). In the patients with an islet cell or medullary tumour and an elevated tumour marker, the marker did not further increase. Of the 12 carcinoid patients evaluable for a symptomatic response, ten (83%) experienced a relieve of symptoms. IFN alpha-2b dose reduction or discontinuation due to toxicity was necessary in three and ten patients, respectively. No neutralising IFN alpha-2b antibodies developed despite prolonged treatment. In conclusion, IFN alpha-2b had a beneficial effect in patients with progressive tumours, while long-term IFN alpha-2b treatment did not augment neutralising antibodies. In view of the IFN alpha-2b-related toxicity, administration of IFN alpha-2b on alternating days may be preferable.

The excretion of proinsulin and insulin in urine.

Proinsulin-like components (PLC) and insulin have been measured in 24 hr urine samples from 8 healthy subjects. The mean excretion of PLC was 45.8 ng and that of insulin 314 ng; the PLC: insulin ratio was 0.14. Urinary PLC was increased 3.5 fold in a patient with a pancreatic islet cell tumor and the PLC: insulin ratio was 0.35. The urinary PLC: insulin ratio is lower than that of serum, presumably because of the relatively lower urinary clearance of the larger molecular weight PLC.