The aim of this study was to compare the pituitary (111)In-DTPA-D-Phe1-octreotide uptake measured in 49 patients subjected to the scintigraphy for SS-R expressing tumors not located in the sellar region with that measured in 38 patients with pituitary adenomas. The 87 subjects enrolled in this study were divided into two groups: the first included SSR-expressing tumors (SS-ET), 10 thymomas, 13 differentiated thyroid carcinomas, 4 carcinoids, 5 neuroendocrine tumors, 5 insulinomas, 6 melanomas, 2 renal carcinomas, 2 pheocromocytomas, and 2 parathyroid tumors, while the second included pituitary adenomas, 25 GH-secreting, 4 GH/PRL-mixed and 9 clinically nonfunctioning adenomas (NFA). Planar and single-photon-emission tomography images of the head were obtained 2-4 and 24 hours after the injection of 77-103 MBq of (111)In-DTPA-D-Phe1-octreotide and pituitary uptake was measured by the region of interest method. A 4 point score was used to grade the pituitary-to-blood (T-to-B) ratios: 0=negative; 1 =faint (T-to-B=<1.5); 2=moderate (T-to-B=1.6-3.5); 3=intense (T-to-B=>3.5). In patients with pituitary adenomas, the percent suppression of GH and alpha-subunit levels after 6-12 months of octreotide treatment (0.3-0.6 mg/day) was correlated to T-to-B ratios. After 2-4 hr from injection, pituitary (111)In-DTPA-D-Phe1-octreotide uptake was moderate/intense in 2 out of 49 SS-ET (4%), 18 out of 29 acromegalics (62%) and 6 NFA (66.6%), while a faint uptake was detected in 4 SS-ET (8%), 8 GH-secreting adenomas (27.5%) and 3 NFA (33.3%). Negative scan was detected in the remaining 43 SS-ET (87.7%) and 3 GH-secreting microadenomas (10.3%). 24 hr after injection, pituitary (111)In-DTPA-D-Phe1-octreotide uptake was moderate/intense in SS-ET (10.2%), 21 GH-secreting adenomas (72.4%), and 9 NFA (100%) while a faint uptake was detectable in 15 SS-ET (30.6%), and 6 GH-secreting adenomas (20.7%). No uptake was visualized in 29 SS-ET, and 2 GH-secreting adenomas. By MRI a pituitary tumor was shown in the 2 SS-ET with early moderate tracer uptake. Normalization of circulating GH/IGF-I levels and suppression of alpha-subunit levels was achieved in 16 of 18 acromegalics (88.9%) and 5 of 6 NFA-bearing patients, respectively, with scan scored 2-3 at early images. Eleven acromegalics (37.9%) and 2 NFA (22.2%) displayed significant tumor shrinkage (> or =30% of baseline size) during long-term octreotide therapy. Both in GH-secreting and in NFA, a significant correlation was found between percent GH or alpha-subunit suppression after 6-12 months of octreotide therapy and T-to-B ratios both in early (r=0.626; p<0.0001 and r=0.738, p=0.003, respectively) and late images (r=0.569; p=0.002 and r=0.8, p=0.01, respectively). In conclusion, the (111)In-DTPA-D-Phe1-octreotide uptake in pituitary adenomas was significantly correlated to octreotide treatment. However, since pituitary (111)In-DTPA-D-Phe1-octreotide uptake was clearly detectable in 40% of patients with SS-ET not located in the pituitary region at 24 hr post-injection, (111)In-DTPA-D-Phe1-octreotide scintigraphy with late pituitary images can not be considered an useful method to predict the chronic responsiveness to octreotide in individual patients. Caution should also be taken in evaluating the results of the scintigraphy with early images in patients with scant uptake before excluding them from treatment.