Effects of fish oil supplementation on platelet survival and ex vivo platelet function in hypercholesterolemic patients.

Little is known about the effects of dietary supplementation on platelet survival with low doses of n-3 and n-6 fatty acids in patients with hypercholesterolemia. The effects of a 6-week intervention with fish oil capsules (daily intake: 216 mg eicosapentaenoic acid, 140 mg docosahexaenoic acid, 390 mg gamma-linolenic acid, and 3480 mg linoleic acid) on in vivo platelet survival (111 In-oxine labeled platelets) and on ex vivo markers of platelet activation were investigated in a placebo-controlled, double-blind study with 26 hypercholesterolemic patients. In vivo platelet survival increased in the fish oil group (T) from a mean of 159+/-14 hours to a mean of 164+/-12 hours (p=0.025), whereas it remained unchanged in the placebo (P) group (T vs. P; p=0.055). Ex vivo, thromboxane B2 decreased from a mean of 225+/-16 to 212+/-21 ng/mL (p=0.003) in T but did not change in P (T vs. P: p=0.002). Malondialdehyde formation was lowered significantly by fish oil supplementation from a mean of 5.49+/-1.3 to 5.12+/-1.05 nM/10(9) platelets, p=0.005, as compared with P (T vs. P; p=0.018). The trendwise decrease in 11-DH-thromboxane B2 plasma levels was not significant nor was the increase in platelet sensitivity to prostaglandin I2 by fish oil. Baseline platelet survival in patients with hyperlipoproteinemia type IIa was not different from those with hyperlipoproteinemia IIb and response to treatment in terms of platelet activation markers was not either. The changes in platelet activation parameters in T were associated with significant reductions in cholesterol (-2.9%), low density lipoprotein cholesterol (-3.5%), and triglycerides (-12.4%). Both ex vivo and in vivo platelet activation parameters exhibited signs of decreased activation by a 6-week diet supplemented with n-3 and n-6 fatty acids, which might be beneficial in reducing atherothrombotic risk, in patients with hyperlipoproteinemia type IIa and IIb.

Accumulation of platelets as a key mechanism of human erection.

In this study, the role of platelets in the human erectile response was assessed. Twenty patients with erectile dysfunction were studied by means of (111)In-oxine-platelets and blood pool imaging using 99mTc. Seventeen patients received intracavernously prostaglandin E1, and three patients received papaverine together with phentolamine. In patients who responded with erection, an increase by between 16 to 137% platelets/ml and a rapid platelet accumulation in the penis during the initial phase of erection were observed. In patients without erection, no change in local platelet concentration occurred. It is likely that platelets play a major role in human erection, probably by temporary activation, thereby regulating venous outflow.

Examination of co-complexes for radiolabeling of platelets in positron emission tomographic studies.

Oxine, tropolonate, and mercaptopyridine-N-oxide (MPO) have been widely used with 111In for platelet labeling. The use of positron emission tomography (PET) radioisotopes for platelet labeling would offer a higher sensitivity and resolution over conventional imaging. The medium half-life PET radioisotope 55Co (t1/2 = 18.2 hours) would enable quantitative uptake and cell kinetic studies with radiolabeled platelets. To identify the optimal complex for radiolabeling of platelets with 55Co, we investigated the platelet uptake of 57Co-oxine, 57Co-tropolonate, and 57Co-MPO in varying different parameters. The platelet uptake of Co-complexes was generally low (5-12%), dependent on time and temperature of incubation and density of platelets but independent of the amount of radioactivity. These findings are not promising for potential PET application.

The effect of various antibiotics on the labelling efficiency of human white blood cells with 111In-oxine.

Earlier clinical studies revealed that in patients suffering from chronic osteomyelitis (n = 10) undergoing antibiotic therapy the white blood cell scanning missed the right diagnosis in 40% of cases, whereas all the acute untreated cases (n = 6) were imaged correctly. Thus, it was suspected that an impaired labelling efficiency and white blood cell function might have been causative. Retrospective analysis of labelling efficiency exhibited no difference between patients on antibiotics (n = 12) and those not on antibiotics (n = 29). Prospective cellular viability testing in 81 patients, 71 of whom were on various antibiotics, using latex particles (phagocytosis) and the Trypan blue exclusion test, did not reveal any different function behaviour either. Examining the labelling efficiency (after 111In-oxine and 111In-oxine-sulphate labelling), recovery, half-life and viability of white blood cells of 107 patients undergoing therapy with various antibodies as compared to controls, it becomes evident that the antibiotic therapy is not causative of the clinical difference observed.

Platelet labeling with 67Ga chelates.

68Ga-labeled platelets could be useful for positron emission tomographic (PET) studies. In order to identify the optimal chelate for radiolabeling of platelets with 68Ga, we investigated the platelet uptake of 67Ga-oxine, -tropolone and -MPO. The platelet uptake of 67Ga-oxine and -tropolone is very low (< 5%). The platelet uptake of 67Ga-MPO, in contrast, increases with platelet density (highest at 10(9) platelets/ml) up to 18%. Our data provide evidence that only 68Ga-MPO could be useful for PET-studies.

Unusual imaging of varicose veins after radiolabeling of autologous low-density lipoproteins.

LDL-radiolabeling with various isotopes (123I, 125I, 131I, 111In, 99mTc and 67Ga, among others) has been used for imaging the arterial wall, monitoring the LDL-kinetics and in particular to assess vascular surface lining and foam cell content. From 286 patients studied with 111In-LDL scintigraphy, only 9 patients presented clinical varicosis. In 2 of these 9 patients a predominant imaging of varicose veins has been shown with scintigraphy, while in the other 7 patients no positive scintigraphic imaging could be detected. In vitro and in vivo perfusion experiments did not reveal an explanation for this unusual results. The reason for that positive LDL-uptake into varicose veins is unknown. These findings indicate that localized LDL-uptake has to be interpreted carefully in order to avoid potential false positive results.

Radionuclide vascular imaging and characterization of human metabolic endothelial surface lining.

Atherosclerotic vascular disease is the leading cause of death in the Western world. Early diagnostic non-invasive imaging is thus of key interest. Despite a large number of successful attempts in experimental conditions, radionuclide vascular imaging in human has not been very successful. Why is that? Experimental lesions are well defined and homogenous with respect to age, size, intensity and structure. Morphological and biochemical evaluations after radionuclide imaging demonstrate excellent correlation in experimental animals. Human lesions, in contrast, are extremely heterogeneous. Certain aspects, such as lesion monitoring (platelets, low-density lipoprotein) do work. Targeting specific antigens in atherosclerotic lesions with a variety of different antibodies, however, has not succeeded. If we learn to better understand functional imaging information vascular imaging data eventually are better than widely considered as a consequence of a lacking comparative standard for the functional activity of the vascular wall. More basic experimental information is required to improve application and optimize information. Stem cell research is the next upcoming approach to give nuclear medicine a chance to demonstrate its clinical value in a rapidly developing new discipline.

Platelet function after single [153Sm]EDTMP therapy in prostate cancer.

AIM: Aim of the study was to assess whether [153Sm] EDTMP therapy at a low-dose is associated with platelet activation. METHODS: In 29 patients suffering from metastatic prostate cancer platelet count and various platelet function parameters have been monitored for 2 months after a single (the first) application of 1.1 GBq mCi [153Sm]EDTMP. RESULTS: After 3 days insignificant signs of platelet activation (increase in malondialdehyde, adenosine diphosphate-induced platelet aggregation, decreased platelet sensitivity) occur, normalizing rapidly. At the nadir of platelet count (3-4 weeks) platelet aggregation response in non-count adjusted samples is somewhat lower, while activity per cell (count adjusted samples) is unchanged. Platelet proteins do not change at all. Insignificant activation of platelet function at day 3 is interpreted as an indicator of mild oxidation injury, late aggregation response changes in non-adjusted samples seem only to reflect temporarily decreased number of circulating platelets. Samarium-153-EDTMP therapy at doses (1.1 GBq) used in the Vienna-protocol is not associated with a significantly altered functional behavior of platelets. CONCLUSIONS: We conclude that a single dose of 1.1 GBq 153Sm-EDTMP does not significantly affect in vivo and ex vivo platelet function.

Adsorption of technetium-99m tetrofosmin and technetium-99m furifosmin on plastic syringes.

Some groups have reported that adsorption of radiopharmaceuticals on disposable plastic syringes can reach levels of almost 50%. This high loss of radioactivity stimulated us to carry out similar studies. Our measurements were done in combination with patient studies. Therefore, we used 2-ml syringes, all of the same brand. The radioactivity in the syringe was measured immediately before and after injection. a total of 500-600 MBq technetium-99m labelled tetrofosmin or technetium-99m furifosmin was administered to 48 patients using four different injection techniques (n = 6 for each technique with each tracer): with needles, 1 min blood incubation at 22 degrees C, 10 or 30 min after preparation of the tracer; with butterflies, 1 min blood incubation at 22 degrees C, 10 or 30 min after preparation of the tracer. Neither in syringes nor in needles or butterflies did more than 7% of the initial radioactivity remain. The entire residual activity in syringe plus needle or syringe plus butterfly together never exceeded the 9% limit. Furthermore, in a pilot study we measured the remaining radioactivity in the vial; here, too, we found no more than 14% of total radioactivity. These findings indicate that total retention of radioactivity during elution and application of 99mTc-tetrofosmin and 99mTc-furifosmin with material used in our setting does not approach relevant amounts.

Platelet viability (aggregation, migration, recovery) after radiolabelling from hypercholesterolemics using various tracers (oxine, oxine-sulphate, tropolone, MPO).

Earlier results indicated a diminished labelling efficiency and recovery negatively linked to actual cholesterol and lipoprotein values in hyperlipoproteinemics. This study was designed to examine whether other alternative tracers exhibit similar results and to study the influence on platelet viability in the presence or absence of PGI2. We demonstrate that no substantial difference occurs between the four tracers concerning labelling efficiency and recovery in normo- and hypercholesterolemics. Cholesterol severely affects the labelling parameters for all the tracers to a comparable extent. The absolute platelet function varies considerably, however, the percent changes in normo- and hypercholesterolemics seen before and after the labelling procedure do not differ significantly. PGI2 improves recovery in general, however, without affecting labelling efficiency or in vitro viability testing. As prolonged incubation further increases labelling efficiency, the presence and extent of hyperlipoproteinemia should be known in order to avoid poor labeling and viability and subsequently poor clinical results.

Prevalence of a shortened prostacyclin half-life in plasma in healthy adults: results of a screening investigation.

Out of a total of 1,981 adults (956 males, 1,025 females; aged 16-71 yr) undergoing a screening investigation for elevated cholesterol only 3 healthy participants with pathologically enhanced prostaglandin 12 (PG12) degradation in plasma in vitro were discovered. The PG12 half-life in these three screenings was shorter than 60 sec and persisted during several follow-up checks. In one patient a familial defect was discovered. Diseases known to be associated with this disturbance in PG12 metabolism have been excluded. The mean half-life of PG12 in 1,978 people amounted to 10.71 +/- 1.93 min. It still needs to be clarified whether this rare disturbance in PG12 metabolism is causally related to, or only associated with, thromboembolic events. A possible predisposition should be elucidated by regular monitoring of affected persons.

A head-to-head comparison between technetium-99m-tetrofosmin and technetium-99m-MIBI scintigraphy to evaluate suspicious breast lesions.

The aim of this study was to assess the diagnostic value of technetium-99m-tetrofosmin and technetium-99m-MIBI in a head-to-head comparison. Both radiopharmaceuticals are routinely used for detecting breast cancer. In a prospective, open, diagnostic trial, the two radiopharmaceuticals were administered randomly on different days to the same 101 women suffering from 103 breast tumours. Planar images and single photon emission computer tomography (SPET) were performed. After histological examination of the tumours, sensitivity, specificity and positive and negative predictive value were compared. 99mTc-tetrofosmin and 99mTc-MIBI showed low sensitivity in planar images (44% vs 46%, respectively). SPET improved sensitivity (70% vs 69%, respectively). Specificity in planar images was 83% and 87%, and it was even lower using SPET (70% vs 78%, respectively). Positive predictive value in planar images was 76% vs 81%, and it was not changed by SPET. Negative predictive value was low in planar images (54% vs 57%, respectively), but it was improved by using SPET (65% vs 67%, respectively). In conclusion, 99mTc-tetrofosmin and 99mTc-MIBI scintigraphy show similar diagnostic value in assessing suspicious breast lesions.