Addition of 131I-MIBG to PRRT (90Y-DOTATOC) for Personalized Treatment of Selected Patients with Neuroendocrine Tumors.

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for metastatic neuroendocrine tumors. Delivering a sufficient tumor radiation dose remains challenging because of critical-organ dose limitations. Adding 131I-metaiodobenzylguanidine (131I-MIBG) to PRRT may be advantageous in this regard. Methods: A phase 1 clinical trial was initiated for patients with nonoperable progressive neuroendocrine tumors using a combination of 90Y-DOTATOC plus 131I-MIBG. Treatment cohorts were defined by radiation dose limits to the kidneys and the bone marrow. Subject-specific dosimetry was used to determine the administered activity levels. Results: The first cohort treated subjects to a dose limit of 1,900 cGy to the kidneys and 150 cGy to the marrow. No dose-limiting toxicities were observed. Tumor dosimetry estimates demonstrated an expected dose increase of 34%-83% using combination therapy as opposed to 90Y-DOTATOC PRRT alone. Conclusion: These findings demonstrate the feasibility of using organ dose for a phase 1 escalation design and suggest the safety of using 90Y-DOTATOC and 131I-MIBG.

Modeling combined radiopharmaceutical therapy: a linear optimization framework.

In this paper, we investigate a previously proposed mathematical model describing the effects that an innovative combined radiopharmaceutical therapy might have on the delivery of radiation to the tumor and limiting critical organs. While focused on a specific dual agent therapy, this investigation will prove mathematically that for any two therapeutic radiopharmaceuticals with different limiting critical organs the model provides patient specific conditions under which combination therapy is superior to single agent therapy. In addition, this paper outlines general methods for calculating the amounts of administered radioactivity for each drug required to optimize tumor radiation dose. We also consider extensions of this model to include an arbitrary number of independent radiopharmaceuticals and/or other treatment factors.

Technical Note: Single time point dose estimate for exponential clearance.

OBJECTIVE: Although personalized dosimetry may be desirable for radionuclide therapy treatments, the multiple time samples required to determine the total integrated activity puts a burden on patients and clinic resources. The aim of this paper is to demonstrate that when some prior knowledge is known about the tracer kinetic parameters, the total integrated activity (and thus radiation dose) can be estimated from a single time sample. METHODS: Mathematical derivations have been performed to generate equations for the total integrated activity in terms of a single time sample of activity for monoexponential and biexponential clearance. Simulations were performed using both exponential models where the rate constants and associated parameters were randomly sampled from distributions with a known mean. The actual total integrated activity for each random sample was compared with the estimated total integrated activity using the mean value of the parameters. Retrospective analysis of 90 Y DOTATOC data from a clinical trial provided a comparison of actual kidney dose with the estimated kidney dose using the single time point approach. RESULTS: The optimal sampling time for the single point approach was found to be equal to the mean time of the rate constant. The simulation results for the monoexponential and biexpoential models were similar. Regressions comparing the actual and estimated total integrated activity had very high correlations (r2  > 0.95) along with acceptable standard errors of estimate, especially at the optimal sampling point. The retrospective analysis of the 90 Y DOTATOC data also yielded similar results with an r2  = 0.95 and a standard error of estimate of 61 cGy. CONCLUSIONS: In situations where there is prior knowledge about the population averages of kinetic parameters, these results suggest that the single time point approach can be used to estimate the total integrated activity and dose with sufficient accuracy to manage radionuclide therapy. This will make personalized dosimetry much easier to perform and more available to the community.

90Y-DOTATOC Dosimetry-Based Personalized Peptide Receptor Radionuclide Therapy.

Pretherapy PET with 86Y-DOTATOC is considered the ideal dosimetry protocol for 90Y-DOTATOC therapy; however, its cost, limited availability, and need for infusion of amino acids to mimic the therapy administration limit its use in the clinical setting. The goal of this study was to develop a dosimetric method for 90Y-DOTATOC using 90Y-DOTATOC PET/CT and bremsstrahlung SPECT/CT and to determine whether dosimetry-based administered activities differ significantly from standard administered activities. Methods: This was a prospective phase 2 trial of 90Y-DOTATOC therapy in patients with somatostatin receptor-positive tumors. 90Y-DOTATOC was given in 3 cycles 6-8 wk apart. In the first cycle of therapy, adults received 4.4 GBq and children received 1.85 GBq/m2; the subsequent administered activities were adjusted according to the dosimetry of the preceding cycle so as not to exceed a total kidney dose of 23 Gy and bone marrow dose of 2 Gy. The radiation dose to the kidneys was determined from serial imaging sessions consisting of time-of-flight 90Y-DOTATOC PET/CT at 5 h after therapy and 90Y-DOTATOC bremsstrahlung SPECT/CT at 6, 24, 48, and 72 h. The PET/CT data were used to measure the absolute concentration of 90Y-DOTATOC and to calibrate the bremsstrahlung SPECT kidney clearance data. The radiation dose to the kidneys was determined by multiplying the time-integrated activity (from the fitted biexponential curve of renal clearance of 90Y-DOTATOC) with the energy emitted per decay, divided by the mass of the kidneys. Results: The radiation dose to the kidneys per cycle of 90Y-DOTATOC therapy was highly variable among patients, ranging from 0.32 to 3.0 mGy/MBq. In 17 (85%) of the 20 adult patients who received the second and the third treatment cycles of 90Y-DOTATOC, the administered activity was modified by at least 20% from the starting administered activity. Conclusion: Renal dosimetry of 90Y-DOTATOC is feasible using 90Y-DOTATOC time-of-flight PET/CT and bremsstrahlung SPECT/CT and has a significant impact on the administered activity in treatment cycles.

Recent advances in SPECT imaging.

SPECT is a rapidly changing field, and the past several years have produced new developments in both hardware technology and image-processing algorithms. At the component level there have been improvements in scintillators and photon transducers as well as a greater availability of semiconductor technology. These devices permit the fabrication of smaller and more compact systems that can be customized for particular applications. New clinical devices include high-count sensitivity cardiac SPECT systems that do not use conventional collimation and the introduction of diagnostic-quality hybrid SPECT/CT systems. While there has been steady progress with reconstruction algorithms, exciting new processing algorithms have become commercially available that promise to provide substantial reductions in SPECT acquisition time without sacrificing diagnostic quality. Preclinical small-animal SPECT systems have become a major focus in nuclear medicine. These systems have pushed the limits of SPECT into the submillimeter range, making them valuable molecular imaging tools capable of providing information unavailable from other modalities.

A segmentation-based method for metal artifact reduction.

RATIONALE AND OBJECTIVES: We propose a novel segmentation-based interpolation method to reduce the metal artifacts caused by surgical aneurysm clips. MATERIALS AND METHODS: Our method consists of five steps: coarse image reconstruction, metallic object segmentation, forward-projection, projection interpolation, and final image reconstruction. The major innovations are 2-fold. First, a state-of-the-art mean-shift technique in the computer vision field is used to improve the accuracy of the metallic object segmentation. Second, a feedback strategy is developed in the interpolation step to adjust the interpolated value based on the prior knowledge that the interpolated values should not be larger than the original ones. Physical phantom and real patient datasets are studied to evaluate the efficacy of our method. RESULTS: Compared to the state-of-the-art segmentation-based method designed previously, our method reduces the metal artifacts by 20-40% in terms of the standard deviation and provides more information for the assessment of soft tissues and osseous structures surrounding the surgical clips. CONCLUSION: Mean shift technique and feedback strategy can help to improve the image quality in terms of reducing metal artifacts.

The Impact of Fatigue on Satisfaction of Search in Chest Radiography.

RATIONALE AND OBJECTIVES: To assess the nature of the satisfaction of search (SOS) effect in chest radiography when observers are fatigued; determine if we could replicate recent findings that have documented the nature of the SOS effect to be due to a threshold shift rather than a change in diagnostic accuracy as in earlier film-based studies. MATERIALS AND METHODS: Nearing or at the end of a clinical workday, 20 radiologists read 64 chest images twice, once with and once without the addition of a simulated pulmonary nodule. Half of the images had different types of "test" abnormalities. Decision thresholds were analyzed using the center of the range of false-positive (FP) and true-positive (TP) fractions associated with each receiver operating characteristic (ROC) point for reporting test abnormalities. Detection accuracy was assessed with ROC technique and inspection time was recorded. RESULTS: The SOS effect was confirmed to be a reduction in willingness to respond (threshold shift). The center of the FP range was significantly reduced (FP = 0.10 without added nodules, FP = 0.05 with added nodules, F(1,18) = 19.85, P = 0.0003). The center of the TP range was significantly reduced (TP = 0.39 without added nodules, TP = 0.33 with added nodules, F(1,18) = 10.81, P = 0.004). CONCLUSIONS: This study suggests that fatigue does not change the nature of the SOS effect, but rather may be additive with the SOS effect. SOS reduces both TP and FP responses, whereas fatigue reduces TPs more than FPs.

Effect of fatigue on reading computed tomography examination of the multiply injured patient.

Our goal was to ascertain how fatigue affects performance in reading computed tomography (CT) examinations of patients with multiple injuries. CT images with multiple fractures from a previous study of satisfaction of search (SOS) were read by radiologists after a day of clinical work. Performance in this study with fatigued readers was compared to a previous study in which readers were not fatigued. Detection accuracy for obvious injuries was not affected by fatigue, but accuracy for subtle fractures was reduced ([Formula: see text]). An SOS effect on decision thresholds was evident mirroring recent studies. Without fatigue, readers spent more time interpreting and reporting findings as the number of the injuries increased. When fatigued, readers did not increase reading time as fracture number increased. Without fractures, reading time for not-fatigued and fatigued readers was the same ([Formula: see text]) but was significant ([Formula: see text]) with an added subtle fracture. The difference increased with a major injury ([Formula: see text]) and increased further with both a major injury and subtle fracture ([Formula: see text]). Fatigue and multiple abnormalities have independent effects on detection performance but do interact in determining search time.

Potential increased tumor-dose delivery with combined 131I-MIBG and 90Y-DOTATOC treatment in neuroendocrine tumors: a theoretic model.

UNLABELLED: (131)I-Metaiodobenzylguanidine (MIBG) and (90)Y-DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) have been used as radiotherapeutic agents for treating neuroendocrine tumors. The tumor dose delivered by these agents is often insufficient to control or cure the disease. However, these 2 agents used together could potentially increase tumor dose without exceeding the critical organ dose because the dose-limiting tissues are different. In this paper, we investigate the conditions in which combined-agent therapy is advantageous and we quantify the expected tumor-dose gain. METHODS: A series of equations was derived that predicted the optimal combination of agents and the fractional increase in tumor dose available from combined-agent therapy with respect to either (131)I-MIBG or (90)Y-DOTATOC. The results obtained from these derivations were compared with direct dose calculations using published dosimetric organ values for (131)I-MIBG and (90)Y-DOTATOC along with critical organ-dose limits. Tumor dose was calculated as a function of the tumor-dose ratio, defined as the (90)Y-DOTATOC tumor dose per megabecquerel divided by the (131)I-MIBG tumor dose per megabecquerel. Comparisons were made between the dose delivered to tumor with single-agent therapy and the dose delivered to tumor with combined-agent therapy as a function of the tumor-dose ratio and the fraction of activity contributed by each agent. RESULTS: The dose model accurately predicted the optimal combination of agents, the range at which combined-agent therapy was advantageous, and the magnitude of the increase. For the published organ dosimetry and critical organ-dose limits, combined-agent therapy increased tumor dose when the tumor-dose ratio was greater than 0.67 and less than 5.93. The maximum combined-agent tumor-dose increase of 68% occurred for a tumor-dose ratio of 2.57, using 92% of the maximum tolerated (90)Y-DOTATOC activity supplemented with 76% of the maximum tolerated activity of (131)I-MIBG. Variations in organ dose per megabecquerel and dose-limiting values altered both the magnitude of the increase and the range at which combined-agent therapy was advantageous. CONCLUSION: Combining (131)I-MIBG and (90)Y-DOTATOC for radiotherapy of neuroendocrine tumors can significantly increase the delivered tumor dose over the dose obtained from using either agent alone. Prior knowledge of the normal-organ and tumor dosimetry of both agents is required to determine the magnitude of the increase.

AAPM Task Group 108: PET and PET/CT shielding requirements.

The shielding of positron emission tomography (PET) and PET/CT (computed tomography) facilities presents special challenges. The 0.511 MeV annihilation photons associated with positron decay are much higher energy than other diagnostic radiations. As a result, barrier shielding may be required in floors and ceilings as well as adjacent walls. Since the patient becomes the radioactive source after the radiopharmaceutical has been administered, one has to consider the entire time that the subject remains in the clinic. In this report we present methods for estimating the shielding requirements for PET and PET/CT facilities. Information about the physical properties of the most commonly used clinical PET radionuclides is summarized, although the report primarily refers to fluorine-18. Typical PET imaging protocols are reviewed and exposure rates from patients are estimated including self-attenuation by body tissues and physical decay of the radionuclide. Examples of barrier calculations are presented for controlled and noncontrolled areas. Shielding for adjacent rooms with scintillation cameras is also discussed. Tables and graphs of estimated transmission factors for lead, steel, and concrete at 0.511 MeV are also included. Meeting the regulatory limits for uncontrolled areas can be an expensive proposition. Careful planning with the equipment vendor, facility architect, and a qualified medical physicist is necessary to produce a cost effective design while maintaining radiation safety standards.

Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use in noninvasive radiological imaging of therapeutic gene transfer.

INTRODUCTION: Noninvasive analysis of therapeutic transgene expression is important for the development of clinical translational gene therapy strategies against cancer. To image p53 and MnSOD gene transfer noninvasively, we used radiologically detectable dual-expressing adenoviral vectors with the human sodium iodide symporter (hNIS) as the reporter gene. METHODS: Dual-expressing adenoviral vectors were constructed with hNIS cloned into E3 region and therapeutic genes, either MnSOD or p53, recombined into the E1 region. Steady-state mRNA levels of hNIS were evaluated by real-time polymerase chain reaction. hNIS function was determined by iodide uptake assay and MnSOD, and p53 protein levels were assessed by Western blots. RESULTS: 125I- accumulation resulting from hNIS expression in both Ad-p53-hNIS- and Ad-MnSOD-hNIS-infected MDA-MB-435 cells could be visualized clearly on phosphorimaging autoradiograph. Iodide accumulation increased with increasing adenovirus titer, and there was a linear correlation between iodide uptake and dose. p53 and MnSOD protein levels increased as a function of adenovirus titer, and there was a direct positive correlation between p53 and MnSOD expression and hNIS function. P53 and MnSOD overexpression inhibited cell growth in the dual-expressing adenoviral vector-infected cells. CONCLUSIONS: Radiological detection of hNIS derived from dual-expressing adenoviral vectors is a highly effective method to monitor therapeutic gene transfer and expression in a noninvasive manner.

A new software tool for removing, storing, and adding abnormalities to medical images for perception research studies.

RATIONALE AND OBJECTIVES: Image perception studies have been difficult to perform using clinical images because of the problems associated with obtaining proven abnormalities and appropriate normal controls. The objective of this research was to develop and evaluate interactive software that allows the seamless removal, archiving and insertion of abnormal areas from computed tomography (CT) lung image sets for use in image perception research. MATERIALS AND METHODS: The software tools for removing, archiving, and adding lesions are described in detail. The efficacy of the software to remove abnormal areas of lung CT studies was evaluated by having radiologists select the one altered image from a display of four. The software for adding lesions was evaluated by having radiologists classify displayed CT slices with lesions as real or artificial along with their confidence level. RESULTS: Observers could not reliably detect when images had been altered by the software. In the lesion-removal experiment, the observers correctly identified the altered display in only 15.8 +/- 2.8 of 56 sets. In the lesion-add experiment, the observers correctly identified the artificially placed lesions in 38.2 +/- 3.9 of 77 sets. The frequency distribution of the correct responses did not differ from that expected from chance selection. CONCLUSIONS: The results from both of these experiments demonstrate that radiologists could not distinguish between original and altered images. We conclude that this software can be used with volumetric CT lung images for creating normal control and target data sets for medical image perception research.

Trauma in CT: The Role of Severe Injury on Satisfaction of Search Revised.

PURPOSE: The satisfaction-of-search (SOS) effect occurs when an abnormality on an image is missed because another is found. The aim of this experiment was to test whether severe distracting fractures control the magnitude of SOS on other fractures when both appear in a single CT image. METHODS: The institutional review board approved this study. The experimental (SOS) condition included 35 cervical spine CT cases, all of which contained severe cervical spine injuries. For each of these cases, a similar case was found that had no injuries. Image modification software was developed to add simulated fractures to each pair of cases, with and without a major injury. Sixteen different minor fractures were added to 16 of the 35 pairs of images. The 35 cases without native injuries constituted a control (non-SOS) condition mixed in a random order. Twenty radiologists read 35 mixed cases in each of two sessions. False-positive evaluations were collected only for cases without simulated fractures. RESULTS: An SOS effect on the detection of simulated fractures was not observed. There was a nonsignificant (P = .07) finding of poorer detection in the presence of cases with severe injuries. However, the magnitude of the effect was no greater than has been observed for less severe distracting injuries. CONCLUSIONS: The outcome agrees with the results of two previous experiments that failed to yield an SOS effect associated with detecting severe injuries, suggesting that the severity of a distracting injury does not determine whether a second injury is discovered.

The Influence of a Vocalized Checklist on Detection of Multiple Abnormalities in Chest Radiography.

RATIONALE AND OBJECTIVES: Although a checklist has been recommended for preventing satisfaction of search (SOS) errors, a previous research study did not demonstrate that benefit. However, observers in that study had to turn away from the image display to use the checklist. The current study tested a vocalized checklist to avoid this constraint. MATERIALS AND METHODS: A total of 64 chest computed radiographs, half containing various "test" abnormalities, were read twice by 20 radiologists, once with and once without the addition of a simulated pulmonary nodule. Readers used a vocalized checklist-directing search. Receiver operating characteristic (ROC) detection accuracy and decision thresholds were analyzed to study the effects of adding the nodule on detecting the test abnormalities. RESULTS: Adding nodules induced a substantial reluctance to report the other abnormalities (P < 0.001), as had been the case in the most recent study of the SOS effect in radiography. CONCLUSIONS: The vocalized checklist did not reduce nor eliminate the SOS effect on readiness to report further abnormalities. Although useful for organizing search and reporting, particularly among students, a vocalized checklist does not prevent SOS effects.

Satisfaction of Search in Chest Radiography 2015.

RATIONALE AND OBJECTIVES: Two decades have passed since the publication of laboratory studies of satisfaction of search (SOS) in chest radiography. Those studies were performed using film. The current investigation tests for SOS effects in computed radiography of the chest. METHODS: Sixty-four chest computed radiographs half demonstrating various "test" abnormalities were read twice by 20 radiologists, once with and once without the addition of a simulated pulmonary nodule. Receiver-operating characteristic detection accuracy and decision thresholds were analyzed to study the effects of adding the nodule on detecting the test abnormalities. Results of previous studies were reanalyzed using similar modern techniques. RESULTS: In the present study, adding nodules did not influence detection accuracy for the other abnormalities (P = .93), but did induce a reluctance to report them (P < .001). Adding nodules did not affect inspection time (P = .58) so the reluctance to report was not associated with reduced search. Reanalysis revealed a similar decision threshold shift that had not been recognized in the early studies of SOS in chest radiography (P < .01) in addition to reduced detection accuracy (P < .01). CONCLUSIONS: The nature of SOS in chest radiography has changed, but it is not clear why. ADVANCES IN KNOWLEDGE: SOS may be changing as a function of changes in radiology education and practice.

Multimodality noninvasive imaging of gene transfer using the human sodium iodide symporter.

UNLABELLED: In this study we investigated the feasibility of using radionuclide accumulation mediated by the human sodium iodide symporter (hNIS) gene in conjunction with various imaging modalities as a reporter system to noninvasively monitor the expression of transgenes delivered for gene therapy. METHODS: NIS-expressing adenovirus (Ad-hNIS) was delivered in vitro to MB-435 breast carcinoma cells. NIS-mediated accumulation of (125)I(-), (99m)TcO(4)(-), and (76)Br(-) by the cells was visualized using autoradiography, gamma-camera scintigraphy, and PET imaging, respectively. RESULTS: For all imaging modalities, signal intensity generated by the cells correlated linearly both with the amount of Ad-hNIS and with the activity of radionuclide added to the cells. CONCLUSION: hNIS-mediated cellular accumulation of radionuclide was clearly visualized by all 3 imaging modalities tested. This preliminary study demonstrates the feasibility of using hNIS for monitoring the location and magnitude of expression of genes delivered during gene therapy.

Contamination levels in blood samples drawn from the injection intravenous line.

PURPOSE: Securing two intravenous lines, one for injection and one for blood sampling, can be nearly impossible in compromised patients, therefore, a need exists to quantify the potential error when simplified techniques are employed. METHOD: Two venous catheters were placed. 2-deoxy-2-[18F]fluoro-glucose (FDG) was infused through one of the catheters. Venous blood samples were drawn from each line. Triplicate aliquots of plasma were analyzed in duplicate. RESULTS: Concentrations from the infusion line were 2.0% higher than the concentrations from the noninfusion line. The average error was 3.3%, 2.0%, and 0.7% higher for the first, second, and third samples, respectively. CONCLUSIONS: Blood sampling through the infusion catheter is a viable alternative to the placement of separate venous catheters. Sampling from the injection catheter, even with tubing flush and replacement, will potentially incur small (generally < 10%) over-estimations in concentration in initial samples. Subsequent sampling reduces the error to essentially zero by the third sample.

Can FDG-PET reduce the need for mediastinoscopy in potentially resectable nonsmall cell lung cancer?

BACKGROUND: Few fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) nonsmall cell lung cancer (NSCLC) trials have had sufficient patients to adequately evaluate PET for mediastinal staging. We question whether once PET is performed, is mediastinoscopy necessary? METHODS: We performed a 5-year retrospective analysis of operable patients with known or suspicious NSCLC. Standard PET techniques were used. Inclusion criteria were (1) surgical mediastinal nodal sampling by mediastinoscopy within 31 days of the PET and (2) definitive diagnosis. RESULTS: There were 237 patients who met the evaluation criteria; ninety-nine patients with NSCLC and 138 with suspicious lesions (137 men and 100 women; aged 20 to 88 years). The PETs were performed from 0 to 29 days before mediastinoscopy (median, 7 days). The standardized uptake value for the primary lesion was 0 to 24.6 (7.9+/-5.0). Nine primary lesions had no FDG uptake (1 benign, 8 NSCLCs). Seventy-one patients (31%) had mediastinal PET positive disease, and 44 patients (19%) had histologic positive mediastinal disease; N2 41 patients (17%) and N3 9 patients (4%). In 6 patients (3%), the initial frozen sections were negative, but PET positivity encouraged further biopsies that were positive for cancer. The PET sensitivity was 82%, specificity 82%, accuracy 82%, negative predictive value 95%, and positive predictive value was 51%. All primary lesions with a standardized uptake value less than 2.5 and a negative mediastinal PET were negative histologically (n = 29). Logistic regression analysis resulted in 100% specificity for PET in this group. CONCLUSIONS: In NSCLC PET may reduce the necessity for mediastinoscopy when the primary lesion standardized uptake value is less than 2.5 and the mediastinum is PET negative. Accepting this approach in our patient population, the need for mediastinoscopy would have been reduced by 12%.

99mTc-depreotide tumour uptake in patients with non-Hodgkin's lymphoma.

BACKGROUND: 99mTc-depreotide (NeoTect) is a synthetic somatostatin analogue, which binds to somatostatin receptor (SSTR) subtypes 2, 3 and 5. Imaging patients with non-Hodgkin's lymphoma (NHL) using the somatostatin analogue In-pentetreotide (Octreoscan) has demonstrated the feasibility of identifying lymphoma sites with this class of peptide radiopharmaceutical. SSTR peptides can be labelled with beta emitters and, if sufficient tumour uptake relative to normal organs can be demonstrated, therapeutic applications can be considered. METHODS: In this prospective Institutional Review Board (IRB)-approved study, patients with NHL and a recent computed tomography (CT) examination were eligible. Whole-body and selected single-photon emission computed tomography (SPECT) imaging was performed 1 h after intravenous injection of 99mTc-depreotide. Images were compared with CT scan findings. The radioactivity concentration of 99mTc-depreotide in abdominal/pelvic tumour sites, together with normal organs, was determined and expressed as the percentage of injected activity per gram of tissue (%IA x g). RESULTS: Paired CT and 99mTc-depreotide images for three patients with indolent and six with aggressive NHL revealed abnormal 99mTc-depreotide uptake corresponding to the tumour seen on CT in seven of these patients. In three of the patients, all known tumour sites were detected on 99mTc-depreotide images. The mean %IA x g for nine abdominal/pelvic tumour foci from four patients was found to be 0.004% (range, 0.001-0.007%). The mean tumour to bone marrow activity concentration ratio in these four patients was found to be 0.94 (range, 0.33-1.40), whereas the tumour to kidney ratio was 0.53 (range, 0.16-0.80). CONCLUSIONS: Levels of 99mTc-depreotide in tumour suggest at least the possibility of potential therapy with beta emitter-labelled SSTR peptides; however, depreotide itself appears not to be a suitable candidate as a targeting agent due to the relatively high bone marrow concentration.