A case of antibody formation against octreotide visualized with ¹¹¹In-octreotide scintigraphy

A case of antibody formation in a patient with carcinoid syndrome is described. The patient was treated with octreotide in dosages up to 1.5 mg/day. Serum samples were analysed for the presence of octreotide antibodies before and after 20 months of octreotide treatment. In-vivo 111In-octreotide scintigraphy was performed before and during therapy, and after antibodies had developed. Before treatment, no serum antibodies against octreotide were detected. After 20 months of treatment, they were detectable up to a 1:115 serum dilution. The serum binding of 125I-Tyr3-octreotide was blocked by adding excess unlabelled Tyr3-octreotide, indicating the presence of specific octreotide antibodies. Before treatment, a normal distribution of radioactivity in the spleen and kidneys, irregular uptake in the liver due to metastases, and a hot spot in the lower abdomen were found during 111In-octreotide scintigraphy. After antibodies had developed, increased radioactivity over the heart and high background radioactivity in the abdomen with only faint visualization of the spleen, liver, and kidneys were found, indicating a prolonged presence of 111In-octreotide in the blood resulting from its being bound to antibodies. Increased radioactivity was also seen at the injection sites of the drug in the upper legs. In-vitro incubation of biopsy tissue from this site with 125I-Tyr3-octreotide revealed diffuse guanosine triphosphate (GTP) independent specific binding non-G-protein linked binding of labelled octreotide. This report describes the characteristic abnormalities during in-vivo 111In-octreotide scintigraphy in a patient with octreotide antibodies. These consisted of high background radioactivity due to prolonged circulation of antibody coupled 111In-octreotide together with visualization of the injection sites, which most probably results from local accumulation of antibodies.</p

Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial

Purpose: Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting 90Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5mm of 90Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide 213Bi with a mean tissue range of 81µm may have a more favourable toxicity profile. Therefore, we evaluated locally injected 213Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality. Methods: In a pilot study, we included five patients with critically located gliomas (WHO grades II-IV). After diagnosis by biopsy, 213Bi-DOTA-substance P was locally injected, followed by serial SPECT/CT and MR imaging and blood sampling. Besides feasibility and toxicity, the functional outcome was evaluated. Results: Targeted radiopeptide therapy using 213Bi-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. 213Bi-DOTA-substance P showed high retention at the target site. MR imaging was suggestive of radiation-induced necrosis and demarcation of the tumours, which was validated by subsequent resection. Conclusion: This study provides proof of concept that targeted local radiotherapy using 213Bi-DOTA-substance P is feasible and may represent an innovative and effective treatment for critically located gliomas. Primarily non-operable gliomas may become resectable with this treatment, thereby possibly improving the prognosi

Somatostatin receptor imaging: The presence of somatostatin receptors in rheumatoid arthritis

Objective. To investigate the in vivo and in vitro expression of somatostatin receptors (SS-R) on synovial membranes of patients with rheumatoid arthritis (RA). Methods. The joints of 14 consecutive patients with active RA, 4 patients with severe osteoarthritis (OA), and 30 control patients were studied. The somatostatin analog [111In-DTPA-D-Phe1]-octreotide was used for in vivo SS-R scintigraphy, and the somatostatin analog [125I-Tyr3]-octreotide for in vitro SS-R autoradiography. Results. Seventy-six percent (220 of 290) of the painful joints and 76% (207 of 274) of the swollen joints of the patients with RA were visualized by SS-R scintigraphy. The degree of pain and swelling correlated well with positive scintigraphy findings in the joints (P < 0.0001). In 2 of the RA patients who underwent scintigraphy, as well as in 4 of 5 other patients, in vitro studies of the synovial membranes showed the presence of specific SS-R. In patients with OA, uptake of radioactivity in the affected joints was significantly lower than that in patients with RA. None of the joints of the control patients demonstrated uptake of radioactivity. Conclusion. SS-R are present in the synovial tissue of p

The use of somatostatin receptor scintigraphy in the differential diagnosis of pancreatic duct cancers and islet cell tumors

OBJECTIVE: In the present study, the diagnostic value of somatostatin receptor scintigraphy (SRS) was evaluated in the preoperative workup in patients with pancreatic duct cancers and islet cell tumors, as well as in the follow-up of these patients. METHODS: Twenty-six patients with suspected primary pancreatic duct cancers and 48 patients with islet cell tumors were studied. The SRS was performed using the radionuclide-labeled somatostatin analogue 111In-octreotide. Another group of 12 patients who were still alive more than 3 years after pancreaticoduodenectomy for pancreatic duct adenocarcinomas also underwent SRS. RESULTS: In 31 (65%) of 48 patients, the primary pancreatic islet cell tumor as well as its often previously not yet recognized metastases could be visualized. In contrast, none of the 26 pancreatic adenocarcinomas or their metastases could be seen. In 5 of 12 patients who were alive more than 3 years after pancreaticoduodenectomy for pancreatic duct adenocarcinomas, metastatic lesions were visualized at SRS. In retrospect, these patients were not operated on for adenocarcinomas but for "nonfunctioning" islet cell tumors. CONCLUSIONS: The present study supports the concept that SRS has a place in the preoperative differential diagnosis of islet cell tumors and pancreatic duct cancers as well as in the follow-up, especially in those cases in which no tumor histologic analysis was obtained, or the pathologic examination of the tumor tissue had not included special staining procedures for neuroendocrine characteristics. Our results also indicate that the evaluation of the results of investigations on the role of surgery or radiation therapy and chemotherapy or both in pancreatic duct cancer have to be interpreted with caution, if no histologic analysis and staining for neuroendocrine characteristics was performed

Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl 2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η 6-bip)Os(4-CO 2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η 6-p-cym)RuCl(dap)] + (p-cym = p-cymene) (5), and [(η 6-p-cym)RuCl(imidazole-CO 2H)(PPh 3)] + (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC 50 = 63 ± 2 μ in MCF-7 cells and IC 50 = 26 ± 3 μ in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC 50 = 45 ± 2.6 μ in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically. © 2012 American Chemical Society