Technetium-99m-HDP uptake characteristics in equine fractures: a retrospective study

Bone scintigraphy is a very sensitive diagnostic tool to detect elevated bone metabolism. In cases of fractures and fissure fractures, the radiopharmaceutical uptake in the bone is said to be increased within a few hours after the injury. In this retrospective study, the scintigraphic uptake characteristics at the fracture site of 36 horses with radiographically confirmed fractures or fissure fractures were evaluated. Uptake ratios between the fracture region and adjacent normal bone or soft tissue activity respectively were calculated and compared to different anamnestic and radiographic data. The overall sensitivity of bone scintigraphy was 94.4% (34 positive cases out of 36). In the 36 horses, no correlation between the age of the fracture and the radiopharmaceutical uptake was found. However, there seems to be a lack of sensitivity in early detection of equine pelvic fractures when a standing bone scintigraphy examination protocol is used.

[Acute "difficult" gastrointestinal bleeding]

Gastrointestinal bleeding with its point of origin outside the reach of conventional gastro- and colonoscopy represents an extraordinary diagnostic and therapeutic challenge. Bleeding may originate from the small bowel distal to the duodenojejunal junction (middle gastrointestinal bleeding) or from the biliary tree (haemobilia) or from the pancreatic ductal system (haemosuccus pancreaticus). This particular type of gastrointestinal bleeding is often intermittend and caused by a variety of different pathologies. Angiography is the diagnostic method of choice for further investigation. It allows precise localization of the bleeding site and simultaneous interventional therapy (embolization/coiling). The importance of further diagnostic modalities such as scintigraphy, capsule endoscopy, push-enteroscopy and double-balloon-enteroscopy is discussed.

Histomorphologic evaluation of extracorporeal shock wave therapy of the fourth metatarsal bone and the origin of the suspensory ligament in horses without lameness

OBJECTIVE: To determine via histologic examination and scintigraphy the effect of focused extracorporeal shock wave therapy (ESWT) on normal bone and the bone-ligament interface in horses. ANIMALS: 6 horses without lameness. PROCEDURE: Origins of the suspensory ligament at the metacarpus (35-mm probe depth) and fourth metatarsal bone (5-mm probe depth) were treated twice (days 0 and 16) with 2,000 shocks (energy flux density, 0.15 mJ/mm2). One forelimb and 1 hind limb were randomly treated, and the contralateral limbs served as nontreated controls. Bone scans were performed on days -1 (before ESWT), 3, 16, and 19. Histomorphologic studies of control and treated tissues were performed on day 30. RESULTS: ESWT significantly increased the number of osteoblasts but caused no damage to associated soft tissue structures and did not induce cortical microfractures. A significant correlation between osteoblast numbers and radiopharmaceutical uptake was noticed on lateral views of the hind limb on days 3 and 16 and on caudal views of the forelimb on day 3. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ESWT has the potential to increase osteoblast numbers in horses. The correlation between increased osteoblast numbers and radio-pharmaceutical uptake 3 days and 16 days after the first ESWT suggested that stimulation of osteogenesis occurred soon after ESWT. No damage to bone or the bone-ligament interface should occur at the settings used in this study, and ESWT can therefore be administered safely in horses.

[Disorders of the origin of the suspensory ligament in the horse: a diagnostic challenge]

Lameness in horses due to pain originating from the proximal metacarpal/metatarsal region remains a diagnostic challenge. In cases of obvious lameness the pain can be localised to this region by diagnostic anaesthesia. Because a variety of disorders can cause lameness in this region different imaging modalities including radiography, ultrasonography and scintigraphy should be used to arrive at an accurate diagnosis. Even though a precise anatomic-pathologic diagnosis can still be an enigma, because not only bone and joints, but also soft tissue structures including the proximal suspensory ligament, its origin at the proximal metacarpus/ metatarsus, its fascia, the superficial fascia, as well as the intermetacarpal/metatarsal ligaments, the accessory ligament of the deep digital flexor tendon and both digital flexor tendons may be involved. Magnet resonance tomography (MRT) shows a high diagnostic sensitivity in imaging soft tissue structures and bone. In horses MRT is still at the beginning. The MRT appearance of the proximal metacarpal/metatarsal region has not yet been evaluated in detail and there are only few anatomic studies of the origin of the suspensory ligament in horses. The first experiences showed, that more gross and histologic examinations are necessary to fully interpret MRT-images and to differentiate pathologic alterations from clinically not relevant variations.

Increased uptake of 111In-octreotide in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is characterized by an uncontrolled accumulation and activation of lung fibroblasts. A modulation of fibroblast activation has been observed in various systems with octreotide, a synthetic somatostatin analog with strong affinity for the somatostatin receptor subtype 2 (sst2). One aim of our study was to evaluate the expression of somatostatin receptors in the lungs of patients with IPF. A second aim was to evaluate the relationship between 111In-octreotide uptake and the effect of pulmonary fibrosis as assessed by lung function tests and parameters and by radiologic findings. METHODS: We investigated 11 patients with IPF, 6 patients with pulmonary fibrosis associated with systemic sclerosis (SSc), and 19 patients with disease not of the lung (control patients). The expression of somatostatin receptors was evaluated in vivo using 111In-octreotide scintigraphy. We evaluated the relationship between 111In-octreotide uptake and the activity of pulmonary fibrosis as assessed by lung function tests, bronchoalveolar lavage (BAL) cellularity, and high-resolution CT (HRCT) of the chest. Planar images and thoracic SPECT (24 h) were performed after injection of 222 MBq of 111In-octreotide. Lung uptake was quantified using the lung-to-background ratio (L/B). In addition, the expression of sst2 was evaluated in vitro, in frozen lung-tissue samples using autoradiography, and in human cultures of lung fibroblasts using a ligand-binding assay. RESULTS: Compared with lung uptake in control patients (median L/B, 1.25; range, 1.14-1.49), lung uptake was increased in all 11 IPF patients (median L/B, 2.63; range, 1.59-3.13; P < 0.001) and in 4 of 6 SSc patients (median L/B, 1.68; range, 1.42-2.16). The L/B was lower in SSc patients than in IPF patients (P = 0.011). Increased uptake correlated with the alteration of lung function (carbon monoxide diffusing capacity [rho = -0.655; P = 0.038], diffusing capacity for carbon monoxide and alveolar volume ratio [rho = -0.627; P = 0.047], vital capacity [rho = -0.609; P = 0.054], and total lung capacity [rho = -0.598; P = 0.058]) and with the intensity of alveolitis (total BAL cellularity [rho = 0.756; P = 0.045], neutrophil counts [rho = 0.738; P = 0.05]), and HRCT fibrosis score (rho = 0.673; P = 0.007). Autoradiography suggested that vascular structures were a prominent binding site. Lung fibroblasts expressed somatostatin receptors in vitro as measured by binding assay. CONCLUSION: Our preliminary results identified an increased expression of sst2 in (mainly idiopathic) pulmonary fibrosis. Lung uptake correlates with the alteration of lung function and with the intensity of alveolitis.

[(99m)Tc]Demotate 2 in the detection of sst(2)-positive tumours: a preclinical comparison with [(111)In]DOTA-tate

PURPOSE: The aim of this study was to evaluate [(99m)Tc]Demotate 2 ([(99m)Tc-N(4) (0-1),Asp(0),Tyr(3)]octreotate) as a candidate for in vivo imaging of sst(2)-positive tumours and to compare it with [(111)In]DOTA-tate ([(111)In-DOTA(0),Tyr(3)]octreotate). METHODS: Labelling of Demotate 2 with (99m)Tc was performed at room temperature using SnCl(2) as reductant in the presence of citrate at alkaline pH. Radiochemical analysis involved ITLC and HPLC methods. Peptide conjugate affinities for sst(2) were determined by receptor autoradiography on rat brain cortex sections using [DOTA(0),(125)I-Tyr(3)]octreotate as the radioligand. The affinity profile of Demotate 2 for human sst(1)-sst(5) was studied by receptor autoradiography in cell preparations using the universal somatostatin radioligand [(125)I][Leu(8),(D: )Trp(22),Tyr(25)]somatostatin-28. The internalisation rates of [(99m)Tc]Demotate 2 and [(111)In]DOTA-tate were compared in sst(2)-positive and -negative control cell lines. Biodistribution of radiopeptides was studied in male Lewis rats bearing CA20948 tumours. RESULTS: Peptide conjugates showed selectivity and a high affinity binding for sst(2) (Demotate 2 IC(50)=3.2 nM and DOTA-tate IC(50)=5.4 nM). [(99m)Tc]Demotate 2, like [(111)In]DOTA-tate, internalised rapidly in all sst(2)-positive cells tested, but not in sst(2)-negative control cells. After injection in CA20948 tumour-bearing rats both radiopeptides showed high and specific uptake in the sst(2)-positive organs and in the implanted tumour and rapid excretion from non-target tissues via the kidneys. CONCLUSION: [(99m)Tc]Demotate 2, similarly to the known sst(2)-targeting agent [(111)In]DOTA-tate, showed promising biological qualities for application in the scintigraphy of sst(2)-positive tumours.

[Acute lower gastrointestinal bleeding--an evidence-based algorithm for diagnosis and treatment]

Novel means to locate and treat lower gastrointestinal bleeding (lGB) allow to reduce the rate of required surgical interventions and help to limit the extend of resection. The risk stratification of patients with lGB is the primary step of our recommended treatment algorithm. Accordingly, risk stratifying instruments, which are only partly validated up to now, are gaining significance in lGB. Whereas, gastro-duodenoscopy and colonoscopy prior to angiography or scintigraphy are established diagnostic tools, capsule enteroscopy offers a novel approach to hemodynamic stable patients with lGB that are difficult to localize. With its every increasing sensitivity, Angio-Computer Tomography is likely to replace scintigraphy and diagnostic angiography in the very near future. In addition, recent advances in superselective microembolisation have been shown to have the potential rendering surgical interventions in a majority of patients with acute lGB unnecessary. The extend of required surgical resection is largely dependent on the success to localize the bleeding source of prior diagnostics. Only if the source is identified, a limited segmental resection should be performed. Should surgery be required, we suggest to maintain the effort to localize the bleeding, either by prior laparoscopy and/or by intraoperative entero-colonoscopy. Eventually, if the source of bleeding remains unclear total colectomy with ileorectal anastomosis represents the procedure of choice in patients with acute lGB.

Liver transplantation for patients with metastatic endocrine tumors: single-center experience with 15 patients

In contrast to other secondary liver malignancy, orthotopic liver transplantation (OLT) is considered as a treatment modality for nonresectable endocrine liver metastases in selected patients. However, only few series have assessed patient selection criteria and long-term results, and no reports have focused on the impact of new technologies in this regard. Between 1992 and 2004, 28 patients with malignant endocrine tumors underwent evaluation for OLT according to our protocol. Data were entered into a prospective database. During pretransplant evaluation, somatostatin receptor scintigraphy detected extrahepatic metastases not diagnosed in standard imaging in 10 patients. Of them, 3 showed aberrant Ki67 labeling results. One patient was excluded from further evaluation due to severe carcinoid heart. Thus far, 15 patients, 10 men and 5 women, aged 37 to 67 years, were subjected to the transplant procedure (11 deceased donor OLT, 3 living donor liver transplantations, and 1 cluster transplantation). Four patients died during the hospital treatment. The median follow-up of the discharged patients was 60.8 months. The actuarial patient survival was 78.3% at 1 year and 67.2% at 5 years. The actuarial 1-, 2-, and 5-year tumor-free survival amounted to 69.4%, 48.3%, and 48.3%, respectively. Two patients underwent surgery for isolated tumor recurrence. In 2 patients, peptide receptor radiotherapy was carried out because of multilocular recurrent disease. In conclusion, liver transplantation is a realistic therapeutic option for highly selected patients with hepatic metastases of endocrine tumors. Our strategy, which implements strict pretransplant selection and aggressive surgical approach, in case of disease recurrence, in addition to systemic radiopeptide treatment, led to an excellent long-term survival cure, however, is unlikely to be achieved.

GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting

Peptide hormone receptors overexpressed in human tumors, such as somatostatin receptors, can be used for in vivo targeting for diagnostic and therapeutic purposes. A novel promising candidate in this field is the GLP-1 receptor, which was recently shown to be massively overexpressed in gut and lung neuroendocrine tumors--in particular, in insulinomas. Anticipating a major development of GLP-1 receptor targeting in nuclear medicine, our aim was to evaluate in vitro the GLP-1 receptor expression in a large variety of other tumors and to compare it with that in nonneoplastic tissues. METHODS: The GLP-1 receptor protein expression was qualitatively and quantitatively investigated in a broad spectrum of human tumors (n=419) and nonneoplastic human tissues (n=209) with receptor autoradiography using (125)I-GLP-1(7-36)amide. Pharmacologic competition experiments were performed to provide proof of specificity of the procedure. RESULTS: GLP-1 receptors were expressed in various endocrine tumors, with particularly high amounts in pheochromocytomas, as well as in brain tumors and embryonic tumors but not in carcinomas or lymphomas. In nonneoplastic tissues, GLP-1 receptors were present in generally low amounts in specific tissue compartments of several organs--namely, pancreas, intestine, lung, kidney, breast, and brain; no receptors were identified in lymph nodes, spleen, liver, or the adrenal gland. The rank order of potencies for receptor binding--namely, GLP-1(7-36)amide = exendin-4 >> GLP-2 = glucagon(1-29)--provided proof of specific GLP-1 receptor identification. CONCLUSION: The GLP-1 receptors may represent a novel molecular target for in vivo scintigraphy and targeted radiotherapy for a variety of GLP-1 receptor-expressing tumors. For GLP-1 receptor scintigraphy, a low-background signal can be expected, on the basis of the low receptor expression in the normal tissues surrounding tumors.

Targeting CCK receptors in human cancers

Gut hormone receptors can be over-expressed in several human cancers and represent the basis for receptor-targeted tumor imaging and therapy. A promising receptor for such clinical applications is the cholecystokinin receptor. Cholecystokinin receptors are expressed in numerous neuroendocrine tumors, in particular medullary thyroid carcinomas and neuroendocrine gut tumors, as well as in stromal tumors. Moreover, several radiolabeled CCK or gastrin analogs have been developed allowing to detect these tumors and their metastases in patients using in vivo cholecystokinin receptor scintigraphy, proving the feasibility of targeting CCK receptors in human tumors in vivo.

Unexpected metastatic pheochromocytoma - an unusual presentation

The classic triad of pheochromocytoma consists of episodic headache, sweating, and tachycardia. General clinicians should be aware, however, that this rare entity might present with a wide spectrum of clinical symptoms. We recently observed a noteworthy case of malignant pheochromocytoma where there was a lack of specific symptoms despite an advanced tumor stage. Malignancy is an important cause of mortality. Reliable diagnosis of malignancy depends upon evidence of local invasion, distant metastases, or recurrence. As in our case, new scintigraphic methods, such as 111-In-pentetreotide scintigraphy (Octreoscan), may occasionally reveal 123-I-metaiodobenzylguanidine-negative distant metastases and help to establish an early diagnosis of malignancy. Tumor size, and perhaps even biochemical profile, may be factors increasing the likelihood of a malignant process and may contribute to early identification of patients at risk.

The role of 3D fusion imaging in sentinel lymphadenectomy for vulvar cancer

OBJECTIVES: To evaluate the feasibility of fusion imaging compound tomography (FICT) of CT/MRI and single photon emission tomography (SPECT) versus planar scintigraphy only (plSc) in pre-surgical staging for vulvar cancer. MATERIALS AND METHODS: Analysis of consecutive patients with vulvar cancer who preoperatively underwent sentinel scintigraphy (planar and 3D-SPECT imaging) and CT or MRI. Body markers were used for exact anatomical co-registration and fusion datasets were reconstructed using SPECT and CT/MRI. The number and localisation of all intraoperatively identified and resected sentinel lymph nodes (SLN) were compared between planar and 3D fusion imaging. RESULTS: Twenty six SLN were localized on planar scintigraphy. Twelve additional SLN were identified after SPECT and CT/MRI reconstruction, all of them were confirmed intraoperatively. In seven cases where single foci were identified at plSc, fusion imaging revealed grouped individual nodes and five additional localisations were discovered at fusion imaging. In seven patients both methods identified SLN contra lateral to the primary tumor site, but only fusion imaging allowed to localise iliac SLN in four patients. All SLN predicted on fusion imaging could be localised and resected during surgery. CONCLUSIONS: Fusion imaging using SPECT and CT/MRI can detect SLN in vulvar cancer more precisely than planar imaging regarding number and anatomical localisation. FICT revealed additional information in seven out of ten cases (70%).

Comparison of outcome and recurrence-free survival after sentinel lymph node biopsy and lymphadenectomy in vulvar cancer

OBJECTIVES: Lymph node status is an important prognostic factor in patients with squamous cell carcinoma (SCC) of the vulva. Complete inguinofemoral lymph node dissection (ILND) is accompanied by a high morbidity. Sentinel lymph node biopsy (SLNB) was established for less invasive lymph node (LN) staging. The aim of this study was to evaluate safety of SLNB in terms of accuracy and outcome in a clinical routine setting. METHODS: We retrospectively reviewed the data of patients who underwent SLNB and/or ILND for vulvar SCC in the years 1990-2007. Clinical follow-up was evaluated for histological nodal-negative patients with tumor stage T1 or T2. The false negative rate of SLNB was determined in patients who underwent both SLNB and ILND. RESULTS: Preoperative sentinel lymph node (SLN) visualization by scintigraphy was successful in 95% of all patients. SLNB was false negative in 1/45 inguinae (2.2%). All SLN were detected intraoperatively. During the follow-up period (median 24 months for SLNB and 111 months for ILND), no groin recurrences in initially nodal negative patients occurred (n=34, 59 inguinae). Transient lymph edema occurred in 7/18 patients after ILND (39%) and 2/16 patients (13%) after SLNB. No persistent edemas were found after SLNB and ILND. CONCLUSION: According to our experience SLNB is feasible and accurately predicts LN status of vulvar SCC under clinical routine conditions. SLNB in vulvar cancer seems to be a safe alternative to ILND in order to reduce morbidity of surgical treatment.

(18)F-Immuno-PET: Determination of Anti-CD66 Biodistribution in a Patient with High-Risk Leukemia

The monoclonal antibody anti-CD66 labeled with (99m)Tc is widely used as Scintimun((R)) granulocyte for bone marrow immunoscintigraphy. Further, recently performed clinical radioimmunotherapy studies with [(90)Y]Y-anti-CD66 proved to be suitable for the treatment of hematologic malignancies. Before radioimmunotherapy with [(90)Y]Y-anti-CD66, dosimetric estimations are required to minimize radiotoxicity and determine individual applicable activities. Planar imaging, using gamma-emitting radionuclides, is conventionally carried out to estimate the absorbed organ doses. In contrast, immuno-PET (positron emission tomography) enables the quantification of anti-CD66 accumulation and provides better spatial and temporal resolution. Therefore, in this study, a semiautomated radiosynthesis of [(18)F] F-anti-CD66 was developed, using the (18)F-acylation agent, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). As a proof of concept, an intraindividual comparison between PET and conventional scintigraphy, using (18)F- and (99m)Tc-labeled anti-CD66 in 1 patient with high-risk leukemia, is presented. Both labeled antibodies displayed a similar distribution pattern with high preferential uptake in bone marrow. Urinary excretion of [(18)F] F-anti-CD66 was increased and bone marrow uptake reduced, in comparison to [(99m)Tc]Tc-anti-CD66. Nevertheless, PET-based dosimetry with [(18)F] F-anti-CD66 could provide additional information to support conventional scintigraphy. Moreover, [(18)F]F-anti-CD66 is ideally suited for bone marrow imaging using PET.

The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.