fMRI connectivity as a biomarker of antipsychotic treatment response: A systematic review.

BACKGROUND: Antipsychotic drugs are the first-choice therapy for psychotic episodes, but antipsychotic treatment response (AP-R) is unpredictable and only becomes clear after weeks of therapy. A biomarker for AP-R is currently unavailable. We reviewed the evidence for the hypothesis that functional magnetic resonance imaging functional connectivity (fMRI-FC) is a predictor of AP-R or could serve as a biomarker for AP-R in psychosis. METHOD: A systematic review of longitudinal fMRI studies examining the predictive performance and relationship between FC and AP-R was performed following PRISMA guidelines. Technical and clinical aspects were critically assessed for the retrieved studies. We addressed three questions: Q1) is baseline fMRI-FC related to subsequent AP-R; Q2) is AP-R related to a change in fMRI-FC; and Q3) can baseline fMRI-FC predict subsequent AP-R? RESULTS: In total, 28 articles were included. Most studies were of good quality. fMRI-FC analysis pipelines included seed-based-, independent component- / canonical correlation analysis, network-based statistics, and graph-theoretical approaches. We found high heterogeneity in methodological approaches and results. For Q1 (N = 17) and Q2 (N = 18), the most consistent evidence was found for FC between the striatum and ventral attention network as a potential biomarker of AP-R. For Q3 (N = 9) accuracy's varied form 50 till 93%, and prediction models were based on FC between various brain regions. CONCLUSION: The current fMRI-FC literature on AP-R is hampered by heterogeneity of methodological approaches. Methodological uniformity and further improvement of the reliability and validity of fMRI connectivity analysis is needed before fMRI-FC analysis can have a place in clinical applications of antipsychotic treatment.

Reverse rhino sign as a radiological sign of low-grade infected reverse shoulder arthroplasty.

INTRODUCTION: Low-grade infections following shoulder surgery are difficult to diagnose. Recently, curved-shaped bony spurs, further mentioned "reverse rhino signs" because of its shape, growing inferior on the glenoid were noticed on X-rays of patients with a reverse shoulder arthroplasty (RSA) and a Cutibacterium acnes (C. acnes) infection. This study aimed to determine the sensitivity and specificity of the reverse rhino sign as a radiological marker for detecting low-grade shoulder infections in RSA. MATERIALS AND METHODS: A diagnostic study was performed including patients who underwent revision surgery of an RSA with perioperative cultures taken. Blinded radiographic evaluation was performed by two orthopedic surgeons for presence of rhino signs, humeral osteophytes, and notching. Efficacy measures of the reverse rhino sign for detecting low-grade infections were determined. Furthermore, results were stratified for notching and gender. RESULTS: Thirty-two revised RSA patients had a low-grade infection and 36 had no infection. Seventeen (53%) patients with infection had a reverse rhino sign present, compared to 6 (17%) in the non-infection group. Sensitivity, specificity, positive and negative predictive value of the reverse rhino sign were, respectively, 53%, 83%, 74%, and 67%. These measures changed to 68%, 77%, 72%, and 74% for patients without notching and to 47%, 100%, 100%, and 8% for males. CONCLUSION: In the absence of a reverse rhino sign in RSA patients, a low-grade shoulder infection is unlikely. Hence, the reverse rhino sign can be used to rule in a low-grade shoulder infection, especially in males and in the absence of notching. Low-grade infections should be considered in patients with unexplained persistent shoulder complaints after RSA placement, especially when a rhino sign is present. For these patients, we advise to perform mini-open biopsy for cultures. LEVEL OF EVIDENCE: Diagnostic level IV.

Short-term clinical results of revision elbow arthroplasty using the Latitude total elbow arthroplasty.

AIMS: Revision total elbow arthroplasty (TEA) is often challenging. The aim of this study was to report on the clinical and radiological results of revision arthroplasty of the elbow with the Latitude TEA. PATIENTS AND METHODS: Between 2006 and 2010 we used the Latitude TEA for revision in 18 consecutive elbows (17 patients); mean age 53 years (28 to 80); 14 women. A Kudo TEA was revised in 15 elbows and a Souter-Strathclyde TEA in three. Stability, range of movement (ROM), visual analogue score (VAS) for pain and functional scores, Elbow Functional Assessment Scale (EFAS), the Functional Rating Index of Broberg and Morrey (FRIBM) and the Modified Andrews' Elbow Scoring System (MAESS) were assessed pre-operatively and at each post-operative follow-up visit (six, 12 months and biennially thereafter). Radiographs were analysed for loosening, fractures and dislocation. The mean follow-up was 59 months (26 to 89). RESULTS: The ROM of the elbow did not improve significantly. The mean EFAS and MAESS scores improved significantly six months post-operatively (18.6 points, standard deviation (sd) 7.7; p = 0.03 and 28.8 points, sd 8.6; p = 0.006, respectively) and continued to improve slightly or reached a plateau. The mean pain scores at rest (Z = -3.2, p = 0.001) and during activity (Z = -3.2, p = 0.001), and stability (Z = -3.0, p = 0.003) improved significantly six months post-operatively. Thereafter scores continued to improve slightly or a plateau was reached. There were no signs of loosening. CONCLUSION: Revision surgery using the Latitude TEA results in improvement of functionality, reduced pain and better stability of the elbow. Improvement of ROM of the elbow should not be expected. Cite this article: Bone Joint J 2016;98-B:1086-92.

Mid-term clinical results of a modern convertible total elbow arthroplasty.

Unlinked, linked and convertible total elbow arthroplasties (TEAs) are currently available. This study is the first to report the clinical results of the convertible Latitude TEA. This was a retrospective study of a consecutive cohort of 63 patients (69 primary TEAs) with a mean age of 60 years (23 to 87). Between 2006 and 2008 a total of 19 men and 50 women underwent surgery. The mean follow-up was 43 months (8 to 84). The range of movement, function and pain all improved six months post-operatively and either continued to improve slightly or reached a plateau thereafter. The complication rate is similar to that reported for other TEA systems. No loosening was seen. Remarkable is the disengagement of the radial head component in 13 TEAs (31%) with a radial head component implanted. Implantation of both the linked and the unlinked versions of the Latitude TEA results in improvement of function and decreased pain, and shows high patient satisfaction at mid-term follow-up.

Pre-clinical evaluation of [(111)In-DTPA-Pro(1), Tyr(4)]bombesin, a new radioligand for bombesin-receptor scintigraphy.

Bombesin (BN) is a 14-amino-acid neuropeptide with a high affinity for the gastrin-releasing peptide receptor. This receptor has been found to be expressed in a variety of tumours, including lung, breast, prostate and pancreas. A newly synthesized BN analogue, [DTPA-Pro(1),Tyr(4)]BN, was shown to be a high-affinity BN-receptor (BNR) agonist, stimulating prolactin secretion from 7315b cells with an IC(50) of 8 nM. The (111)In-labelled analogue was found to bind with high affinity to rat BNR in vitro and in vivo. The radioligand is internalized by BNR-expressing cells, in contrast to DTPA-conjugated BN antagonists. Therefore, we further studied the biodistribution of i.v. injected [(111)In-DTPA-Pro(1),Tyr(4)]BN in rats. High and specific uptake was found in tissues of the gastrointestinal tract, notably pancreas. Uptake of radioactivity was blocked by pre- or co-injection of 100 microgram [Tyr(4)]BN, but not when this was administered 30 min after the radioligand. This suggests BNR-mediated internalization of the radioligand within 30 min. The percentage injected dose (ID) taken up by BNR-positive tissues was a bell-shaped function of the amount (0.01-0.1 microgram) of injected ligand. Next to the pancreas, highest uptake was observed in the kidneys, which was not blocked by excess [Tyr(4)]BN. Dynamic gamma camera studies showed rapid clearance of radioactivity from the blood compartment. Urinary excretion amounted to about 35% ID after 1 hr and to 70% ID after 24 hr, with a total body retention of 10% ID. Specific uptake was found in the BNR-positive CA20948 pancreas tumour and CC531 colon carcinoma in tumour-bearing rats. The CA20948 tumour, inoculated in the hindleg, was also visualized scintigraphically. [(111)In-DTPA-Pro(1), Tyr(4)]BN appears to be a promising radioligand for scintigraphy of BNR-expressing tumours.

Tumour uptake of the radiolabelled somatostatin analogue [DOTA0, TYR3]octreotide is dependent on the peptide amount.

Radiolabelled tumour receptor-binding peptides can be used for in vivo scintigraphic imaging. Recently, the somatostatin analogue [Tyr3]octreotide (D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr(ol)) was derivatized with the chelator DOTA (tetra-azacyclododecane-tetra-acetic acid), enabling stable radiolabelling with both the high-energy beta particle-emitter yttrium-90 and the Auger electron-emitter indium-111. The thus produced radiolabelled compounds are promising for peptide receptor radionuclide therapy. Our previous in vitro and in vivo (rat) experiments with these radiolabelled compounds showed favourable binding and biodistribution characteristics with high uptake and retention in the target organs. We also demonstrated receptor-specific, time- and temperature-dependent internalization of radiolabelled [DOTA0,Tyr3]octreotide in somatostatin receptor subtype 2 (sst2)-positive rat pancreatic tumour cell lines. In this study we have investigated the effects of differences in the amount of injected peptide on tissue distribution of 111In-labelled [DOTA0, Tyr3]octreotide in normal, i.e. non-tumour-bearing, and CA20948 tumour-bearing rats. This was done in order to find the amount of peptide at which the highest uptake in target tissues is achieved, and thereby to increase the potential of radionuclide therapy while simultaneously ensuring the lowest possible radiotoxicity in normal organs. Uptake of radiolabelled [DOTA0,Tyr3]octreotide in sst2-positive organs showed different bell-shaped functions of the amount of injected peptide, being highest at 0.05 (adrenals), 0.05-0. 1 (pituitary and stomach) and 0.25 (pancreas) microg. Uptake in the tumour was highest at 0.5 microg injected peptide. The highest uptake was found at peptide amounts that were lower than those reported for [111In-DTPA0]octreotide ((D-Phe-c(Cys-Phe-D-Trp-Lys-Thr-Cys)-Thr(ol), DTPA = diethylene-triamine-penta-acetic acid), consistent with the higher receptor affinity of the first compound. Our observations of mass-dependent differences in uptake of radiolabelled [DOTA0, Tyr3]octreotide, being the resultant of a positive effect of increasing amounts of peptide on, for example, receptor clustering and a negative effect of receptor saturation, are of consequence for rat radionuclide therapy studies with radiolabelled peptides and may also be of consequence for human radionuclide therapy studies with this compound.

Tissue distribution and metabolism of radioiodinated DTPA0, D-Tyr1 and Tyr3 derivatives of octreotide in rats.

UNLABELLED: Lesions containing somatostatin receptors (SSR) in rats and in man can be visualized in vivo using radiolabeled octreotide (OCT) analogs. SSR scintigraphy was initially performed with [123I-Tyr3]OCT and later with [111In-DTRA0]OCT. With the latter the residence time of radioactivity (111In) in SSR-positive targets is prolonged, most probably due to the DTPA group. Therefore, we hypothesized that its presence might also affect the metabolism of radioiodinated DTPA-OCT analogs. [D-Tyr1]OCT, [DTPA0, D-Tyr1]OCT, [Tyr3]OCT and [DTPA0,Tyr3]OCT were synthesized, and all 4 showed high and specific binding to the SSR in vitro, with IC50 values in the nanomolar range. The rate of internalization of the 4 radioiodinated OCT analogs by mouse AtT20 pituitary tumors cells was in accordance with the IC50 values. The metabolism and tissue distribution of the 4 radioiodinated analogs were investigated in rats at 4, 24 and 48 hours pi, and the tissue vs blood ratios were calculated. High uptake of all OCT analogs was found in the somatostatin receptor-positive tissues at 4 hours, but only remained high at 24 and 48 hours with [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT. Kidney uptake of [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT was also high. Blood clearance and disappearance from muscle was rapid for all 4 analogs. Urinary excretion of [125I-D-Tyr1]OCT, [DTPA0,125I-D-Tyr1]OCT,[125I-Tyr3]OCT and [DTPA0, 125I-Tyr3]OCT amounted to 63%, 67%, 31% and 80% of injected dose respectively. [DTPA0,125I-D-Tyr1]OCT showed highest tissue to blood ratio and residence time in SSR-positive tissues, such as adrenals (ratio: 31, 79, and 66 at 4, 24 and 48 hours respectively) and pancreas (ratio: 14, 48 and 44 at 4, 24 and 48 hours respectively). CONCLUSION: The position of the Tyr residues and the addition of the DTPA group greatly influence the biodistribution of radioiodinated [Tyr]OCT analogs.

Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy.

In vitro octreotide receptor binding of [111In-DOTA0,d-Phe1, Tyr3]octreotide (111In-DOTATOC) and the in vivo metabolism of 90Y- or 111In-labelled DOTATOC were investigated in rats in comparison with [111In-DTPA0]octreotide [111In-DTPAOC). 111In-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of 90Y- or 111In-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2-6 that after injection of 111In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. These findings strongly indicate that 90Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that 111In-DOTATOC is of potential value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours.

Iodine-131 labelled octreotide: not an option for somatostatin receptor therapy.

Gamma-emitting radiopeptides are useful for scintigraphy of tumours on the basis of receptor binding. Likewise, beta-emitting radiopeptides may be used in radionuclide therapy of such tumours. As iodine-131 suggested to be suitable for this purpose, experiments were performed using three somatostatin analogues, in which the effects of coupling of a therapeutic dose of 131I to such peptides were investigated. This study deals with the radioiodination of very small amounts of peptide on a therapeutic scale, the required purification procedures after radioiodination, and the influence of high beta fluxes from 131I on a peptide during radioiodination and purification. Based on the regularly used therapeutic doses of 131I in cancer treatment and our previous experience with [111In-DTPA-D-Phe1]-octreotide, it was assumed that a minimal effective therapeutic dose of 3.7 GBq 131I has to be coupled to a maximum of approximately 100 microg peptide, representing only a slight excess of peptide over 131I. This contrasts with non-peptide radiopharmaceuticals in which high compound to radionuclide ratios are usually used. Labelling at low peptide to radionuclide ratios (low labelling yields) results in the formation of di-iodinated compounds, whereas at high peptide to radionuclide ratios (high labelling yields) mono-iodinated products of low specific activity are formed. Thus, after radioiodination the desired mono-iodinated peptide has to be separated from unreacted iodide, and from di-iodinated and unreacted peptide, as both compounds compete for the receptors. Possible radiolysis of the peptide during labelling and separation steps were investigated by irradiating 30 microgram unlabelled peptide with 370 MBq 131I in a small volume. The peptide composition of the incubation mixtures was investigated by high-performance liquid chromatography after irradiation for 30 min to 24 h. The results showed that the peptide was degraded with a half-life of less than 1 h. During the preparation of a real therapeutic dose (at much higher beta-flux) the peptide will be degraded even faster during the various steps required. In conclusion, intact mono-iodinated 131I-labelled somatostatin analogues for peptide receptor therapy will be difficult to obtain.

In vitro and in vivo studies of substance P receptor expression in rats with the new analog [indium-111-DTPA-Arg1]substance P.

UNLABELLED: We evaluated the potential usefulness of a new radiolabeled substance P (SP) analog, [111In-DTPA-Arg1]SP, as a radiopharmaceutical for the in vivo detection of SP receptor-positive (SPR+) immunologic disorders (i.e., inflammatory bowel disease and arthritis) and tumors (i.e., carcinoid). METHODS: Substance P, [DTPA-Arg1]SP and [3-(p-hydroxyphenyl)propionyl-Arg1]SP (Bolton-Hunter-SP, [BH-SP]) were tested as competitors for 125I-BH-SP to SPR in rat brain cortex membranes. An autoradiographic displacement study of the submandibular gland of the rat with the 125I-BH-SP as radioligand and [DTPA-Arg1]SP as competitor was performed. Tissue distribution and ex vivo autoradiography were studied in rats, with and without pretreatment with the selective nonpeptide antagonist CP96,345 to quantify specific binding. In vivo metabolism of [111In-DTPA-Arg1]SP was performed in control rats. Gamma-camera scintigraphic studies were carried out with control rats to visualize the SPR+ salivary glands in rats bearing the SPR+ transplantable pancreatic tumor CA20948 and in rats with SPR+ adjuvant arthritic joints, which was induced after injection of a homogenate of Mycobacterium tuberculosis. RESULTS: Substance P, [DTPA-Arg1]SP and BH-SP dose-dependently inhibited binding of 125I-BH-SP to SPR in rat brain cortex membranes with IC50 values of 0.2, 4 and 2 nM, respectively. In an autoradiographic displacement study of the submandibular gland with 125I-BH-SP as radioligand, an IC50 of 2.7 nM was found for [DTPA-Arg1]SP. In vivo metabolism of the radiopharmaceutical in the rat revealed a renal clearance rate of 50% of the injected radioactive dose in 30 min and a rapid enzymatic degradation of the radiopharmaceutical, resulting in an effective half-life of the intact radiopharmaceutical in blood of approximately 3 min. Tissue distribution and ex vivo autoradiographic studies in rats showed uptake and specific binding of radioactivity in isolated tumors and submandibular and parotid glands. Optimum SPR+ target-to-background ratios were found 24 hr after injection of [111In-DTPA-Arg1]SP. Visualization of normal SPR+ tissues, such as the salivary glands by gamma camera scintigraphy, after administration of [111In-DTPA-Arg1]SP was demonstrated in untreated rats. Pathological SPR+ processes were visualized both in rats bearing the transplantable pancreatic tumor CA20948 and in those with adjuvant mycobacteria tuberculosis-induced arthritic joints. CONCLUSION: [Indium-111-DTPA-Arg1]SP can be used successfully to visualize SPR+ processes in vivo by gamma camera scintigraphy.

Evaluation in vitro and in rats of 161Tb-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 that 161Tb-DTPA-octreotide is a high-affinity radioligand for somatostatin receptors, with an affinity comparable to that of 111In-DTPA-octreotide. Rat growth hormone secretion inhibition experiments showed that 161Tb-DTPA-octreotide has a similar potency to 111In-DTPA-octreotide. 161Tb-DTPA-octreotide appeared to be taken up even less by the isolated perfused rat liver than 111In-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 of 161Tb-DTPA-octreotide is lower then that of 111In-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 of 161Tb-DTPA-octreotide than with 111In-DTPA-octreotide. Furthermore, these studies demonstrated that the uptake of 161Tb-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 of 161Tb-DTPA-octreotide.(ABSTRACT TRUNCATED AT 250 WORDS)

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 115In-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-D-Phe1]RC-160 has no advantage over [111In-DTPA-D-Phe1]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.

Hepatobiliary handling of iodine-125-Tyr3-octreotide and indium-111-DTPA-D-Phe1-octreotide by isolated perfused rat liver.

Radiolabeled bioactive peptides may show receptor-mediated binding to tumors, making them suitable for scintigraphic imaging. The liver is an important organ for peptide clearance. To gain insight into the uptake and intracellular processing of somatostatin analogs, we compared the hepatobiliary handling of 125I-Tyr3-octreotide and 111In-DTPA-D-Phe1-octreotide, which are successfully used to image somatostatin receptor-positive tumors in vivo in isolated recirculating perfused rat livers. Sixty minutes following administration of the radiolabeled peptides, perfusion medium and biliary radioactivity were analyzed. Radioiodinated Tyr3-octreotide was rapidly cleared by the liver and 60% of the dose was excreted intact into the bile after 60 min. In contrast, 111In-DTPA-D-Phe1-octreotide was not cleared by the liver; medium radioactivity levels remained about constant and only 2% of the dose was found in the bile. These results are in agreement with in vivo findings in rats and humans. We concluded that isolated rat liver perfusion is a good system to rapidly gain insight into the hepatic handling of radiopharmaceuticals.

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 tumors. 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.