In vivo use of a radioiodinated somatostatin analogue: dynamics, metabolism, and binding to somatostatin receptor-positive tumors in man.

Somatostatin analogues, labeled with gamma-emitting radionuclides, are of potential value in the localization of somatostatin receptor-positive tumors with gamma camera imaging. We investigated the application in man of a radioiodinated analogue of somatostatin, 123I-Tyr-3-octreotide, which has similar biologic characteristics as the native peptide. The radiopharmaceutical is cleared rapidly from the circulation (up to 85% of the dose after 10 min) mainly by the liver. Liver radioactivity is rapidly excreted into the biliary system. Until 3 hr after injection, radioactivity in the circulation is mainly in the form of 123I-Tyr-3-octreotide. Thereafter, plasma samples contain increasing proportions of free iodide. Similarly, during the first hours after injection, radioactivity in the urine exists mainly in the form of the unchanged peptide. Thereafter, a progressive increase in radioiodide excretion is observed, indicating degradation of the radiopharmaceutical in vivo. Fecal excretion of radioactivity amounts to only a few percent of the dose. The calculated median effective dose equivalent is comparable with values for applications of other 123I-radiopharmaceuticals (0.019 mSv/MBq).     

Radioiodinated somatostatin analogue RC-160: preparation,biological activity,in vivo application in rats and comparison with [123I-Tyr3]octreotide

We have evaluated the potential usefulness of the radioiodinated octapeptide RC-160, a somatostatin analogue, which might serve as a radiopharmaceutical for the in vivo detection of somatostatin receptor-positive tumours. For this purpose, iodine-123 and iodine-125 labelled RC-160 was tested for biological activity and applied in vivo in rats bearing the transplantable rat pancreatic tumour CA20948, which expresses somatostatin receptors. Our group has recently described the in vivo visualization of such tumours in rats and in humans with the radioiodinated somatostatin analogue [Tyr³]octreotide. Like [¹²³I-Tyr³]octreotide, ¹²³I-RC-160 showed uptake in and specific binding in vivo to somatostatin receptor-positive organs and tumours. However, blood radioactivity (background) was higher, resulting in a lower tumour to blood (background) ratio. We therefore conclude that in this animal model ¹²³I-RC-160 has no advantage over [¹²³I-Tyr³]octreotide as a radiopharmaceutical for the in vivo use as a somatostatin receptor imager, although, like [¹²³I-Tyr³]octreotide, ¹²³I-RC-160 shows specific binding to different somatostatin receptor-positive organs. Recently differences were reported in affinity between somatostatin and its analogues for somatostatin receptors expressed in different human cancers, like those of the breast, ovary, exocrine pancreas, prostate and colon. Therefore ¹²³I-RC-160 might be of interest for future use in humans as a radiopharmaceutical for imaging octreotide receptor-negative tumours. Correspondence to: W.A.P. Breeman, Department of Nuclear Medicine, University Hospital Dijkzigt, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The NetherlandsThe authors wish to thank Dr. Wil Kort, Ineke Hekking-Weyma, Reno Mekes, Marcello Harms and Ina Loeve for their expert assistance during the experiments.     

Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats.

No-carrier-added [18F]altanserin was synthesized by nucleophilic substitution of the corresponding nitro compound with [18F]fluoride in the presence of kryptofix 222 and K2CO3. After purification by preparative HPLC, [18F]altanserin was produced in less than 2 hr with a radiochemical yield of 10% (EOS) and a specific activity of 0.8-1.3 Ci/mumol. In rats, the tracer localized rapidly in the whole brain (0.5% ID/g organ) with a high binding to the frontal cortex. The frontal cortex/cerebellum ratio increased with time and reached a plateau of 11 at 2 hr postinjection. This uptake in S2 receptor regions was saturable and could be blocked by pretreatment with various S2 antagonists. This radiopharmaceutical appears to be more selective for S2 receptor sites than other ligands available today and allows the study of S2 receptors under in vivo conditions.     

Somatostatin analogue scintigraphy in a patient with viral myocarditis

Myocarditis may present clinically with a wide range of manifestations and often remains unrecognized. The diagnosis of myocarditis traditionally has been based on histological findings, but endomyocardial biopsy has a low sensitivity and clinicians are reluctant to proceed with an invasive diagnostic technique. Among newer diagnostic approaches, cardiac magnetic resonance imaging has gained acceptance as an efficient noninvasive tool to determine myocardial inflammation. In this context, imaging with radiolabeled somatostatin analogues could also be relevant because of their ability to delineate inflammatory sites. In conclusion, a case is presented in which somatostatin receptor imaging of the myocardium with (99m)Tc-depreotide tomography was used in the assessment of viral myocarditis.     

A new radiolabelled somatostatin analogue [111In-DTPA-D-Phe1]RC-160: preparation,biological activity,receptor scintigraphy in rats and comparison with [111In-DTPA-D-Phe1]octreotide

We have evaluated the potential usefulness of indium-111 labelled [DTPA-D-Phe¹]RC-160, derived from the octapeptide somatostatin analogue RC-160, as a radiopharmaceutical for the in vivo detection of somatostatin receptor-positive tumours. For this purpose ¹¹¹In-and ¹¹¹In-labelled [DTPA-D-Phe¹]RC-160 was tested for its biological activity, and applied for somatostatin receptor scintigraphy in vivo to rats bearing the transplantable rat pancreatic tumour CA20948, which expresses somatostatin receptors. We previously described the development of the ¹¹¹In-labelled somatostatin analogue [DTPA-D-Phe¹]octreotide and its use in the in vivo visualization of somatostatin receptor-positive tumours in rats and in humans. Like [¹¹¹In-DTPA-D-Phe¹]octreotide, [¹¹¹In-DTPA-D-Phe¹]RC-160 showed uptake in and specific binding in vivo to somatostatin receptor-positive organs and tumours, and the tumours were clearly visualized by gamma camera scintigraphy. However, as compared to [¹¹¹In-DTPA-D-Phe¹]octreotide, blood radioactivity (background) was higher, resulting in a lower tumour to blood (background) ratio. Using this animal model we therefore conclude that [¹¹¹In-DTPA-DPhe¹]RC-160 has no advantage over [¹¹¹In-DTPA-DPhe¹]octreotide as a radiopharmaceutical in the visualization of somatostatin receptors which bind both analogues. However, recent reports suggest the existence of different somatostatin receptor subtypes on some human cancers, which differentially bind RC-160 and not octreotide. These tumours include cancers of the breast, ovary, exocrine pancreas, prostate and colon. [¹¹¹In-DTPA-D-Phe¹]RC-160 might be of interest for future use in such cancer patients as a radiopharmaceutical for imaging somatostatin receptor-positive tumours, which do not bind octreotide.     

A comparison of scintigraphy with radioiodinated MIBG and CT in localizing pheochromocytomas

In order to define the diagnostic roles of MIBG imaging and CT in the detection of pheochromocytomas (pheos), the results obtained in 45 patients suspected of bearing pheo and studied with both modalities were analyzed and compared. Scintigraphy was correctly negative in 22/23 cases, correctly positive in 11/12 adrenal and 5/5 extra-adrenal pheos, and in 4/5 malignant pheos (metastases present in 2 cases were also identified). CT was correctly negative in 20/23 cases (a mass other than a pheo was detected in 3 patients); correctly positive in 12/12 adrenal and 4/5 extra-adrenal pheos and in 5/5 malignant pheos. Sensitivity, specificity and accuracy of scintigraphy and CT were 91% and 95.4%, 95.6% and 87%, 93.3% and 91.1% respectively (differences were not statistically significant). The overall data emphasize the complementary role of 123/131I-MIBG imaging and CT in the location of pheochromocytomas. A flow-chart essentially grounded on the combined use of both these diagnostic modalities is proposed which includes 123/131I-MIBG scintigraphy as a first choice examination.     

腹膜后占位生长抑素受体显像鉴别诊断一例

患者女,41岁,主诉腰部不适1个月,无发热、头痛、恶心、呕吐、腹痛、腹胀、腹泻、头晕、黑矇、大汗等症状。腹部CT发现右侧腹膜后软组织密度肿块;增强CT+三维重建图像示肿块大小约57 mm×40 mm,增强后明显强化,各期强化程度与血管相似,肿块局部与十二指肠分界欠清,下腔静脉呈受压性改变(图1)。     

Preparation and biologic evaluation of a novel radioiodinated benzylpiperazine, 123I-MEL037, for malignant melanoma.

Radiopharmaceuticals that can target the random metastatic dissemination of melanoma tumors may present opportunities for imaging and staging the disease as well as potential radiotherapeutic applications. A novel molecule, 2-(2-(4-(4-(123)I-iodobenzyl)piperazin-1-yl)-2-oxoethyl)isoindoline-1,3-dione (MEL037), was synthesized, labeled with 123I, and evaluated for application in melanoma tumor scintigraphy and radiotherapy. METHODS: The tumor imaging potential of 123I-MEL037 was studied in vivo in C57BL/6J female mice bearing the B16F0 murine melanoma tumor and in BALB/c nude mice bearing the A375 human amelanotic melanoma tumor by biodistribution, competition studies, and SPECT. RESULTS: 123I-MEL037 exhibited high and rapid uptake in the B16F0 melanoma tumor at 1 h (13 %ID/g [percentage injected dose per gram]), increasing with time to reach 25 %ID/g at 6 h. A significant uptake was also observed in the eyes (2 %ID, at 3-6 h after injection) of black mice. No uptake was observed in the tumor or in the eyes of nude mice bearing the A375 tumor. Because of high uptake and long retention in the tumor and rapid body clearance, the mean contrast ratios (MCR) of 123I-MEL037 were 30 and 60, at 24 and 48 h after injection, respectively. At 24 h after injection of mice bearing the B16 melanoma, SPECT indicated that the radioactivity was located predominately in the tumor followed by the eyes, whereas no specific localization of the radioactivity was noted in mice bearing the A375 human amelanotic tumor. In competition experiments, uptake of 123I-MEL037 in brain, lung, heart, and kidney--organs known to contain sigma-receptors--was not significantly different in haloperidol-treated animals compared with control animals. Therefore, reduction of uptake in tumor and eyes of the pigmented mice bearing the B16F0 tumor suggested that the mechanism of tumor uptake was likely due to an interaction with melanin. CONCLUSION: These findings suggested that 123I-MEL037, which displays a rapid and very high tumor uptake, appeared to be a promising imaging agent for detection of most melanoma tumors with the potential for development as a therapeutic agent in melanoma tumor proliferation.     

Bone scintigraphy and somatostatin receptor scintigraphy in pediatric patients with bone involvement in Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a granulomatous disease which can involve multiples sites of the body. Diagnostic imaging is of utmost importance in the management of these patients. Up to now radiographic skeletal survey and bone scintigraphy (BS) have been used to assess bone involvement (both with low specificity). Magnetic resonance imaging (MRI) and CT have been used to assess visceral involvement but with the limitation that they cannot give information about the functional status. Recently somatostatin receptor scintigraphy (SSRS) has been proposed to detect active lesions and to monitor response to treatment. The aim of this study is to assess bone and somatostatin receptor scintigraphy in the detection of bone involvement in LCH in children. Twenty scintigraphies (12 SSRS and 8 BS) were performed in seven patients (3 girls and 4 boys) aged at diagnosis: 18 month-12 years (mean age 6 years). The findings obtained in the scintigraphies were compared with clinical evolution and other imaging techniques. Bone scintigraphy detected all the LCH bone lesions, and discovered one unknown lesion. SSRS scintigraphy visualised the active lesions in 3 patients (clinical and other imaging techniques were also positive). SSRS was negative in one patient classified as disease free and another in clinical remission. SSRS detected 2 new unknown bone lesions, but could not detect LCH bone lesions confirmed in other imaging techniques in 2 patients. Somatostatin receptor and Bone scintigraphy can be used to detect active LCH bone lesions in children and can help to monitor response to treatment. Further studies with more patients are needed to confirm the diagnostic usefulness of these techniques.     

Detection of bone metastases in patients with endocrine gastroenteropancreatic tumors: bone scintigraphy compared with somatostatin receptor scintigraphy.

Scintigraphy with somatostatin analogs is a sensitive method for the staging and therapeutic management of patients with endocrine gastroenteropancreatic (GEP) tumors. The aim of this study was to compare prospectively somatostatin receptor scintigraphy (SRS) using 111n-pentetreotide with bone scintigraphy using 99mTc-hydroxymethylene diphosphonate for the detection of bone metastases. METHODS: One-hundred-forty-five patients with proven endocrine GEP tumors were investigated. Patients were classified according to the presence of bone metastases as indicated by CT, MRI or histologic data. Group I included 19 patients with confirmed bone metastases, and group II included 126 patients without bone metastases. RESULTS: In group I, SRS was positive in all 19 patients with bone metastases, and bone scintigraphy was positive in 17 patients. Bone metastases were found to occur predominantly in patients with liver metastases. In group 11, 5 patients had recent bone surgery for fracture or arthritis. SRS showed bone uptake in 4 of these patients, and bone scanning showed abnormal uptake in 5. In 7 of the remaining 121 group II patients, SRS was negative and bone scanning showed abnormal bone uptake suggesting bone metastases. The detection of bone metastases was of major prognostic value, because 42% of group 1 patients died during a 2-y follow-up. CONCLUSION: In patients with GEP tumors, the accuracy of SRS appears to be similar to that of bone scintigraphy for the detection of bone metastases.     

64Cu-labeled folate-conjugated shell cross-linked nanoparticles for tumor imaging and radiotherapy: synthesis, radiolabeling, and biologic evaluation.

Long-circulating nanoparticles functionalized with ligands for receptors overexpressed by tumor cells have promising applications for active and passive tumor targeting. The purpose of this study was to evaluate 64Cu-radiolabeled folate-conjugated shell cross-linked nanoparticles (SCKs) as candidate agents to shuttle radionuclides and drugs into tumors overexpressing the folate receptor (FR). METHODS: SCKs were obtained by cross-linking the shell of micelles obtained from amphiphilic diblock copolymers. SCKs were then functionalized with folate, fluorescein thiosemicarbazide (FTSC), and 1,4,8,11-tetraazacyclotetradecane-N,N',N',N'-tetraacetic acid (TETA). The specific interaction of SCK-folate with the FR was investigated on KB cells. The biodistributions of 64Cu-TETA-SCK and 64Cu-TETA-SCK-folate were evaluated in athymic mice bearing small-size KB cell xenografts (10-100 mg), whereas the intratumor distributions were investigated by autoradiography in 0.3- to 0.6-g KB cell xenografts. RESULTS: A global solution-state functionalization strategy has been introduced for attaching optimum numbers of targeting and imaging agents onto the SCKs for increasing the efficiency of interaction with cell-surface receptors. Epifluorescence microscopy confirmed the specific interaction of FTSC-SCK-folate with the FR in vitro. 64Cu labeling of TETA-SCKs led to the radiolabeled compounds with 15%-20% yield and >95% radiochemical purity. The biodistribution results demonstrated high accumulation of 64Cu-labeled SCKs in organs of the reticuloendothelial system (RES) (56.0 +/- 7.1 %ID/g and 45.7 +/- 3.5 %ID/g [percentage injected dose per gram] in liver at 10 min after injection for folated and nonfolated SCKs, respectively) and a prolonged blood circulation. No increase of SCK tumor uptake deriving from folate conjugation was observed (5.9 +/- 2.8 %ID/g and 6.0 +/- 1.9 %ID/g at 4 h after injection for folated and nonfolated SCKs, respectively). However, tumor accumulation was higher in small-size tumors, where competitive block of SCK-folate uptake with excess folate was observed. Autoradiography results confirmed the extravasation of radiolabeled SCKs in vascularized areas of the tumor, whereas no diffusion was observed in necrotic regions. CONCLUSION: Despite high RES uptake, the evaluated 64Cu-labeled SCKs exhibited long circulation in blood and were able to passively accumulate in tumors. Furthermore, SCK-folate uptake was competitively blocked by excess folate in small-size solid tumors, suggesting interaction with the FR. For these reasons, functionalized SCKs are promising drug-delivery agents for imaging and therapy of early-stage solid tumors.     

[123I]Mtr-TOCA, a radioiodinated and carbohydrated analogue of octreotide: scintigraphic comparison with [111In]octreotide

Purpose Scintigraphy with maltotriose-[¹²³I]Tyr³-octreotate ([¹²³I]Mtr-TOCA) is compared with [¹¹¹In]DTPA-Phe¹-octreotide ([¹¹¹In]OC) to assess the differences in pharmacokinetics and imaging properties as well as to estimate the therapeutic potential of the corresponding [¹³¹I]Mtr-TOCA.Methods Six patients with somatostatin receptor (sstr)-positive tumours were assessed using a dual-head gamma camera. After injection of 137±28 MBq [¹²³I]Mtr-TOCA, dynamic data acquisition of the upper abdomen (30 min) was performed followed by whole-body scans at 0.5 h, 1 h, 3 h and 20 h as well as by SPECT imaging (tumour) at 2 h. [¹¹¹In]OC scintigraphy was performed by acquiring whole-body scans (4 h, 24 h) and SPECT (24 h). Using a region of interest (ROI) method, tissue and tumour bound activity was assessed and dosimetry performed.Results [¹²³I]Mtr-TOCA shows rapid tumour uptake. Up to 4 h, tumour/organ (tu/org) ratios are stable and generally higher than with [¹¹¹In]OC. From 3 h to 20 h, tu/org ratios increase for spleen, remain stable for liver and decrease significantly for all other tissues. In contrast, with [¹¹¹In]OC, tu/org ratios decrease slightly between 4 h and 24 h for liver, spleen and kidney and increase for all other tissues. On [¹²³I]Mtr-TOCA scintigraphy, a total of 27 lesions are detected, whereas 33 lesions are detected on [¹¹¹In]OC scintigraphy (p=0.50). Effective patient absorbed dose is 1.9±0.9 mSv per 100 MBq [¹²³I]Mtr-TOCA.Conclusion Compared with [¹¹¹In]OC, [¹²³I]Mtr-TOCA enables faster imaging of sstr-positive tumours with a lower radiation burden to the patient. [¹²³I]Mtr-TOCA and [¹¹¹In]OC allow for tumour imaging with almost identical contrast and diagnostic yield. As regards peptide receptor radionuclide therapy, radioiodinated Mtr-TOCA is hampered by limited intratumoural activity retention.     

Somatostatin receptor scintigraphy in pituitary adenomas: a somatostatin receptor density index can predict hormonal and tumoral efficacy of octreotide in vivo.

Previous studies have failed to predict somatostatin analog response with somatostatin receptor scintigraphy in pituitary adenomas. In vitro studies have shown that the density of somatostatin receptors in pituitary tumors might be critical for octreotide response. METHODS: The density of somatostatin receptors was calculated in vivo combining the uptake index obtained from somatostatin receptor scintigraphy and the tumor volume obtained by MRI. The ratio of these two values, called density index (DI), was established in 32 of 37 consecutive patients with pituitary adenomas (11 had growth hormone-secreting adenomas, 4 thyroid-stimulating hormone-secreting and 17 nonfunctioning). It was compared with hormonal response, assessed in 15 secreting adenomas on growth hormone or thyroid stimulating hormone suppression (which was considered significant when it reached at least 50% of basal level), and with tumor shrinkage (which was considered significant when > or =20% of pretherapeutic value) in 12 secreting and 14 nonfunctioning adenomas. RESULTS: In agreement with previous reports, uptake index is not predictive of octreotide response. In contrast, DI predicts both hormonal suppression and tumor shrinkage (P = 0.009 and P = 0.0002, respectively) obtained with octreotide therapy. DI sensitivity, specificity and accuracy were 92% each, and a positive correlation was found between DI and the percentage of tumor shrinkage (r = 0.54, P = 0.004). CONCLUSION: The combination of scintigraphic and MRI data allows the computation of a DI for somatostatin receptors that points out patients who can profit from somatostatin analog treatment.     

Inflammatory bowel disease activity assessment with biologic markers and 99mTc-WBC scintigraphy: are there different trends in ileitis versus colitis?

To evaluate whether scintigraphy with (99m)Tc-labeled white blood cells (WBC) can assess the intensity of bowel inflammation, a large dataset of laboratory values and clinical activity indices was correlated with (99m)Tc-WBC scintigraphy in children with Crohn's disease (CD), ulcerative colitis (UC), and miscellaneous colitis (MC). Also evaluated was whether stratification of children with CD as ileitis versus colitis results in different correlation coefficients for laboratory values versus (99m)Tc-WBC scintigraphy. METHODS: Over a 6-y period, 313 (99m)Tc-WBC studies were performed. A dataset of 2,714 laboratory values is available for analysis. RESULTS: There is a positive correlation between the erythrocyte sedimentation rate (ESR) and large bowel uptake of (99m)Tc-WBC (P < 0.05) and a negative trend with small bowel uptake of (99m)Tc-WBC in children with CD. Similarly, there is a correlation between WBC counts and scintigraphy in most segments of the large bowel and a negative correlation with the small bowel (R = -0.32, P = 0.01) in children with CD. There is a correlation between platelets and (99m)Tc-WBC in children with CD or UC. There is no correlation between the ESR and (99m)Tc-WBC in children with UC or MC. Many clinical activity indices correlate (P < 0.001) with (99m)Tc-WBC in children with CD, but none correlates in children with UC. Numerous laboratory values correlate with each other. There is a negative correlation between protein, albumin, hemoglobin, and hematocrit versus (99m)Tc-WBC scintigraphy in children with CD. In children with UC, there is a negative correlation between hemoglobin and hematocrit versus (99m)Tc-WBC. CONCLUSION: (99m)Tc-WBC scintigraphy, ESR, and WBC counts are good indicators of the inflammatory activity in CD if the inflammation is limited to the large bowel. There is a trend toward an inverse relationship when the inflammation is limited to the small bowel; thus, scintigraphy and the aforementioned markers may be of limited value. This report also demonstrates that (99m)Tc-WBC scintigraphy correlates with clinical activity indices in CD and with numerous biologic markers. In children with UC, scintigraphy with (99m)Tc-WBC and most laboratory markers are of limited value in assessing disease activity.     

Evaluation in vitro and in rats of161Tb-DTPA-octreotide,a somatostatin analogue with potential for intraoperative scanning and radiotherapy

The characteristics of terbium-161 diethylene triamine penta-acetic acid (DTPA) labelled octreotide with respect to specific binding to somatostatin (octreotide) receptors on rat brain cortex membranes, biological activity, uptake and excretion by isolated perfused rat livers and metabolism in vivo in normal and tumour-bearing rats were determined and compared to those of indium-111 DTPA-octreotide. The results of the binding studies demonstrate that¹⁶¹Tb-DTPA-octreotide is a high-affinity radioligand for somatostatin receptors, with an affinity comparable to that of¹¹¹In-DTPA-octreotide. Rat growth hormone secretion inhibition experiments showed that¹⁶¹Tb-DTPA-octreotide has a similar potency to¹¹¹In-DTPA-octreotide.¹⁶¹Tb-DTPA-octreotide appeared to be taken up even less by the isolated perfused rat liver than¹¹¹In-DTPA-octreotide, as almost no tracer disappeared from the perfusion medium. Furthermore, hardly any radioactivity was found in the liver, and excretion into the bile was negligible. The biodistribution studies showed that for octreotide receptor-positive organs, such as pancreas and adrenals, uptake of¹⁶¹Tb-DTPA-octreotide is lower then that of¹¹¹In-DTPA-octreotide. However, as the clearance from the blood of the former compound is faster than that of the latter, the tissue/blood ratio is higher in the case of¹⁶¹Tb-DTPA-octreotide than with¹¹¹In-DTPA-octreotide. Furthermore, these studies demonstrated that the uptake of¹⁶¹Tb-DTPA-octreotide by the renal tubular cells after glomerular filtration can be reduced by administration of lysine or sodium maleate. Increase in urine production before and during the experiment had no effect on the kidney uptake of¹⁶¹Tb-DTPA-octreotide. Finally, it appeared that a maximal labelling efficiency of¹⁶¹Tb-DTPA-octreotide is essential, as with decreasing efficiency the uptake in the octreotide receptor-positive organs decreased, whereas non-specific uptake in the other organs was increased. It is concluded that, on the basis of the favourable physical characteristics of¹⁶¹Tb combined with the in vitro and in vivo studies performed with¹⁶¹Tb-DTPA-octreotide, the latter is a promising radiopharmaceutical for both intraoperative scanning and radiotherapy. Studies in patients need to be performed now to see whether¹⁶¹Tb-DTPA-octreotide can indeed open new therapeutic applications for patients bearing octreotide receptor-positive tumours.     

Radiolabeled somatostatin analog scintigraphy in oncology and immune diseases: an overview

[¹¹¹In-DTPA-D-Phe¹]-octreotide is a new radiopharmaceutical with a great potential for the visualization of somatostatin receptor-positive tumors, granulomas, and diseases in which activated leukocytes play a role. The overall sensitivity of [¹¹¹In-DTPA-D-Phe¹]-octreotide scintigraphy to localize neuroendocrine tumors is high. In several neuroendocrine tumor types, inclusion of somatostatin receptor imaging in the localization or staging procedure may be very rewarding, either in terms of cost-effectiveness, patient management, or quality of life. In our opinion, this holds true for patients with carcinoids, gastrinomas, paragangliomas, small-cell lung carcinoma, and selected cases of patients with insulinomas. The value of [¹¹¹In-DTPA-D-Phe¹]-octreotide scintigraphy in patients with other tumors, such as breast cancer, malignant lymphomas, or in patients with granulomatous diseases, has to be established. Received 19 June 1996; Revision received 28 October 1996; Accepted 6 November 1996     

Ability of somatostatin receptor scintigraphy to identify patients with gastric carcinoids: a prospective study.

Gastric carcinoids are of increasing clinical concern because they may develop in hypergastrinemic states, especially with the increased chronic use of potent acid suppressants that can cause hypergastrinemia. However, gastric carcinoids are difficult to diagnose. Somatostatin receptor scintigraphy (SRS) has a high sensitivity and specificity for localizing carcinoids in other locations. The purpose of this study was to determine whether SRS could localize gastric carcinoids. METHODS: Two groups of patients with Zollinger-Ellison syndrome (ZES) with hypergastrinemia, each having a different increased risk of developing gastric carcinoids, were studied. One hundred sixty-two consecutive patients with ZES were studied prospectively, with 39 having multiple endocrine neoplasia, type 1 (MEN-1) (high increased risk), and 123 not having MEN-1 (low increased risk). Patients were admitted to the hospital initially and then yearly, undergoing SRS with SPECT, upper gastrointestinal endoscopy, and Jumbo Cup biopsies of any gastric abnormalities, as well as random biopsies of the gastric body. Tumor localization studies were also performed. Both the results of the routine SRS interpretation and the results of a masked review, with particular attention to the stomach of high risk MEN-1 patients, were correlated with the gastric biopsy results. RESULTS: Gastric SRS localization was positive in 19 (12%) of 162 patients. Sixteen patients had a gastric carcinoid, and 12 of these patients had SRS localization. The sensitivity of SRS in localizing a gastric carcinoid was 75%, with a specificity of 95%. Positive and negative predictive values were 63% and 97%, respectively. CONCLUSION: SRS is a noninvasive method that can identify patients with gastric carcinoids with a reasonable sensitivity and a high specificity. SRS should prove useful in the treatment of patients with hypergastrinemic states that have an increased incidence of gastric carcinoids. In patients with MEN-1, one must realize that localization in the upper abdomen on SRS may be caused by a gastric carcinoid and not a pancreatic endocrine tumor.     

Synthesis and preliminary biological evaluation of new radioiodinated MMP inhibitors for imaging MMP activity in vivo

Non-invasive measurement of matrix metalloproteinase (MMP) activity in vivo is a clinical challenge in many disease processes such as inflammation, tumor metastasis and atherosclerosis. Therefore, radioiodinated analogues of the non-peptidyl broad-spectrum MMP inhibitor (MMPI) CGS 27023A 1a were synthesized for non-invasive detection of MMP activity in vivo using single photon emission computed tomography (SPECT). The compounds Br-CGS 27023A 1b and HO-CGS 27023A 1d were synthesized from the amino acid D-valine and used as precursors for radioiodinated derivatives of CGS 27023A and their non-radioactive references I-CGS 27023A 1c and HO-I-CGS 27023A 1e. Radioiodination of the precursors with [(123)I]NaI or [(125)I]NaI produced the no-carrier-added MMP inhibitors [(123)I]I-CGS 27023A 1f, [(125)I]I-CGS 27023A 1g, HO-[(123)I]I-CGS27023A 1h, and HO-[(125)I]I-CGS 27023A 1i. In vitro studies showed that the non-radioactive analogues of the MMP inhibitors exhibited affinities against gelatinase A (MMP-2) and gelatinase B (MMP-9) in the nanomolar range, comparable to the parent compound CGS 27023A. In vivo biodistribution using HO-[(125)I]I-CGS 27023A 1i in CL57 Bl6 mice showed rapid blood and plasma clearance and low retention in normal tissues. The preliminary biological evaluation warrant further studies of these radioiodinated MMP inhibitors as potential new radiotracers for imaging MMP activity in vivo.