The scintigraphic evaluation of the pulmonary perfusion pattern of dogs hospitalised with babesiosis.

The possibility of coagulopathy in Babesia canis rossi infections in the canine patient has been suggested in the literature, but minimal work has been done to evaluate the clinicopathological nature of it in further detail. Pulmonary thromboembolism (PTE) has not yet been implicated in canine babesiosis (CB), but may also be one of the causes of the sudden dyspnoea and tachypnoea that are frequently seen in complicated CB patients. The objective of this study was to prospectively evaluate the scintigraphic pulmonary perfusion pattern in hospitalised dogs with babesiosis in an attempt to ascertain whether a scintigraphic pattern consistent with clinically relevant PTE does indeed occur in these patients. The study consisted of a normal control group of 9 mature healthy Beagle dogs (group 1) and a Babesia group with 14 dogs of a variety of breeds that were naturally infected with Babesia (group 2). Pulmonary perfusion scintigraphy was performed after making thoracic radiographs and performing a blood gas analysis in both groups. The scintigraphic images were visually inspected for changes suggestive of PTE, but not a single dog in group 2 had pleural-based, wedge-shaped perfusion defects which would have resulted in a high probability for clinically relevant PTE. The scintigraphic pulmonary perfusion pattern demonstrated was not significantly different between the 2 groups (P = 1.00).

Technetium-99m-HMPAO, technetium-99m-ECD and iodine-123-IMP cerebral blood flow measurements with pharmacological interventions in primates.

UNLABELLED: Technetium-99m-bicisate ethyl cysteinate dimer (ECD) presents a different pattern from cerebral blood flow (CBF) in the subacute phase of cerebral infarction, as measured by PET, perhaps due to lack of oxygen and enzyme activity; this pattern is contrary to that of hexamethyl-propyleneamine oxime (HMPAO) but similar to that of N-isopropyl-[123I]beta-iodoamphetamine ([123I]IMP). This study explores possible CBF differences among HMPAO, ECD and IMP, with various relevant drug interventions. METHODS: Anesthetized adult baboons were used in these SPECT studies. Four studies (n = 6 baboons for each study), one control study and three intervention studies involving intravenous acetazolamide, nimodipine infusion and intramuscular sumatriptan, were followed with 99mTc-HMPAO, 99mTc-ECD and [123I]IMP. The split-dose method was used as follows. For each tracer, intervention data from the second SPECT (SPECT-2) after the second tracer injection (444 MBq) reflected a change in CBF with respect to the baseline SPECT (SPECT-1) data from the initial injection (222 MBq). These changes as a ratio, R (R = SPECT-2/SPECT-1), for each study, and the R values for each tracer were compared to R values from the corresponding control studies, yielding a quantitative estimate of drug effects. RESULTS: There were no significant differences (p > 0.05) between HMPAO and ECD for the control, acetazolamide and sumatriptan studies, but there was indeed a difference between the two for the nimodipine study, indicating a nimodipine-dependent underestimation of CBF with ECD (and also with IMP), with respect to HMPAO. A further significant difference was that larger CBF increases were observed with acetazolamide, as measured with [123I]IMP. CONCLUSION: This is a crucial observation for the clinical interpretation of CBF SPECT data and should direct the choice of tracer for a specific examination.

Long-term treatment with the tetrahydropyridine analog (HPTP) of haloperidol influences dopamine ligand binding in baboon brain. An [123I]iodobenzamide (IBZM) SPECT study.

Haloperidol (HP) and its tetrahydropyridine dehydration product 4-(4-chlorophenyl)-[4-(fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyrid ine (HPTP) are both metabolized in vivo to several pyridinium metabolites with potential neurotoxic properties similar to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), a metabolite of the parkinsonian-inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The effect of long-term HPTP treatment on the central nervous system of baboons (Papio ursinus) was studied using [123I]iodobenzamide (IBZM) and single photon emission computed tomography (SPECT) at 1-14 weeks after termination of HPTP treatment. Striatal dopamine receptor binding was measured semiquantitatively by calculating the IBZM count rate ratios of the basal ganglia to frontal cortex and basal ganglia to cerebellum. Relative striatal perfusion was assessed by similar 99mTc-HMPAO (hexamethylpropylene amine oxime) ratios. Time activity curves of IBZM from the brain structures suggest that HPTP treatment results in a marked reduction in central dopamine ligand binding, and in particular D2-like receptor binding. Increased washout of the ligand from all the brain structures investigated was seen in the HPTP-treated animals, also consistent with reduced binding. Cerebral blood flow in the control and HPTP-treated groups was similar, indicating that this did not account for the reduced dopamine receptor binding of the IBZM ligand. These data suggest that treatment with HPTP induces significant effects on dopamine receptor binding that may contribute to some of the neurological disorders observed in humans undergoing chronic HP treatment.

A comparative cerebral blood flow study in a baboon model with acetazolamide provocation: 99mTc-HMPAO vs 123I(IMP).

Pharmacological interactions are important when nuclear medical procedures are applied to patients under drug therapy, or drug provocation. This study compares in baboon models (regional) cerebral blood flow [(r)CBF] results from 99mTc-HMPAO and 123I-iodoamphetamine [123I(IMP)] each with and without acetazolamide, the latter a suggested drug for testing cerebrovascular reserve. Expected differences in cerebral uptake were observed between the two radio-tracers without acetazolamide. The increase in tracer uptake resulting from acetazolamide is significantly enhanced for 123I(IMP), which could have diagnostic implications.

Evaluation in the baboon model of (99m)Tc-biguanide as a tracer for renal imaging.

Studies in various animal species have recently shown that (99m)Tc-BIG has practical and dosimetric benefits for renal imaging that could probably make it a good alternative to (99m)Tc-2, 3-dimercaptosuccinic acid ((99m)Tc-DMSA). In this study, using the baboon experimental model, the biodistribution of (99m)Tc-BIG and (99m)Tc-DMSA are compared. It is demonstrated that early good contrast imaging and more favourable dosimetry is possible with (99m)Tc-BIG compared to (99m)Tc-DMSA, confirming the quoted previous findings with small animals. Time-activity curves for kidneys and other organs support these findings, and MIRDOSE software provided the dosimetry.

Planar myocardial imaging in the baboon model with iodine-123-15-(iodophenyl)pentadecanoic acid (IPPA) and iodine-123-15-(P-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP), using time-activity curves for evaluation of metabolism.

The purpose of this study was to compare by planar myocardial scintigraphy the kinetics of iodine-123-15-(iodophenyl)pentadecanoic acid (123I-pPPA and 123I-oPPA), and of iodine-123-(p-iodophenyl)-3-R,S-methyl-pentadecanoic acid (BMIPP), firstly in normal baboons, and subsequently after blocking fatty acid oxidation by a carnitine palmitoyl transferase I(CPT1) inhibitor. The induced changes in myocardial metabolism were reflected in the dynamic behaviour of the three tracers. pPPA and oPPA to a large extent, provided information on beta-oxidation changes in the myocardium: beta-oxidation participation changed from 47% and 50%, respectively to 17% and 23% after inhibition. BMIPP provided better images and reflected largely on changed tracer incorporation into the neutral lipid pools. The beta-oxidation contributed only about 10% towards the metabolic pathway of BMIPP. The information obtained in this study could help determine the tracer of choice for SPECT, whereby myocardial viability could optimally be revealed.

Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model.

Bone-seeking radiopharmaceuticals such as ethylenediaminetetramethylene phosphonate (EDTMP) complexes of samarium-153 and holmium-166 are receiving considerable attention for therapeutic treatment of bone metastases. In this study, using the baboon experimental model, multicompartmental analysis revealed that with regard to pharmacokinetics, biodistribution, and skeletal localisation, 166Ho-EDTMP was significantly inferior to 153Sm-EDTMP and 99mTc-MDP. A more suitable 166Ho-bone-seeking agent should thus be sought for closer similarity to 153Sm-EDTMP to exploit fully the therapeutic potential of its shorter half-life and more energetic beta radiation.

In vivo measurements of the cerebral perfusion and cardiovascular effects of the novel guanidine ME10092 in the non-human primate, Papio ursinus.

The novel guanidines N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine (ME 10092) and N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N1-hydroxyguanidine (PR5) were recently reported to exhibit promising cardioprotective activities in myocardial ischaemia and reperfusion in rats. The current study investigated for the first time pharmacological effects of ME10092 in the primate, viz. the Cape baboon Papio ursinus. The effects of ME10092 (1 and 2 mg/kg doses) on the cerebral blood flow, heart rates and the systolic and diastolic blood pressure were investigated after intravenous injection to the baboon under anaesthesia. The cerebral perfusion effects of ME10092 were assessed using Single Photon Emission Computed Tomography according to the split-dose approach and 99mTc-hexamethyl-propylene amine oxime as brain perfusion tracer. The observation that the recovery times from the anaesthesia were unacceptably prolonged excluded doses beyond 2 mg/kg. The data indicate that no cerebral perfusion changes were induced at both the 1 and 2 mg/kg doses of ME10092. Both these doses of ME10092 showed blood pressure and heart rate effects, with the latter being more significant. Decreases in heart rate were seen directly after ME10092 administration reaching levels of about 20% for the 2 mg/kg dose and about 15% for the 1 mg/kg dose at around 6 min post drug administration. A transient decrease in both systolic and diastolic blood pressure was observed for the higher dose. The blood pressure data further suggest an attenuation of the anaesthesia induced increase in pressure usually present in non-intervention studies. ME10092 clearly exhibits mycocardial effects in the non-human primate, similar to the effects previously observed in the ischaemia-reperfusion rat model, where ME10092 showed strong protection.

The influence of cycle length on the radionuclide left ventricular volume curve acquired with a scintillation camera and ECG-triggered data processor.

This study was designed to evaluate the effect of cycle length on the parameters of left ventricular function such as left ventricular ejection fraction (LVEF), ejection rates and ejection times. Radionuclide (in vivo 99mTc-labelled red blood cells) volume curves were obtained from ten chacma baboons. Transoesophageal atrial pacing of the baboon hearts was controlled by a microcomputer. A sequence of four beats was generated during arrhythmic pacing, consisting of two beats of equal cycle lengths, followed by a beat 15% shorter and a subsequent beat after a compensatory pause. Triggering impulses were sent to the data processor coincident with one of these beats until sufficient counts were obtained, before advancing to the next beat. Global LVEFs were found to be influenced by the preceding cycle length, increasing on a previous long cycle and decreasing on a previous short cycle and were even found to be influenced one normal beat on from the unrepresentative cycle. Similar trends were found for ejection times and rates. Discarding specific unrepresentative cycle lengths in order to correct for arrhythmia without attention to the previous cycle and even to the following cycle is therefore inappropriate.

A technique to evaluate bone healing in non-human primates using sequential 99mTc-methylene diphosphonate scintigraphy.

The assessment of bone healing through sequential nuclear medical scintigraphy requires a method of consistent localization of the exact fracture area in each consecutive image as the study progresses. This is difficult when there is surrounding bone activity as in the early stages of trauma, and also if complications should set in. The image profile feature, available from most nuclear medical computer software, facilitates this procedure considerably, as is indicated in the present report on bone healing in baboons. Together with roentgenology and histology a 99mTc-MDP study was in this way successfully done on the healing of long bone fractures experimentally induced in non-human primates. Different surgical implants were used. The results indicate that 99mTc-MDP accurately reflects the physiological activity in bone. The time-activity curves obtained are presently being studied together with extensive histology, bearing possible clinical application in mind.

Gastrointestinal scintigraphy using 99mTc- or 111In-labelled polymer beads.

In order to establish normal and pathological stomach emptying characteristics by external measurement of a radioactive meal using a gamma camera and computer system, it is necessary for the radioactively labelled substance to have the same behaviour in the stomach as the ingested food. Resins containing chelating groups which enable binding to either reduced 99mTcO4- or 111In+3 were tested for their suitability as tracers mixed into solid food. The preparation of such styrene-divinyl-benzene resins containing either triethylenetetramine substituents or the fully carboxymethylated derivatives is discussed, as well as the procedures of labelling with either 99mTc-pertechnetate or 111In-chloride. An evaluation of the resins for gastrointestinal scintigraphy was performed on 3 chacma baboons and a male human volunteer with encouraging results.

A comparison of 111In-labelled polymer beads and 99mTc-Sn-colloid as solid food and semi-solid food tracers for scintigraphic gastric emptying studies.

In order to establish the efficacy of labelling a solid meal and a semi-solid meal with either 111In-labelled polymer beads or 99mTc-tin colloid beagle dogs were fed variously labelled meals of different consistencies and then monitored by scintigraphy for gastric motility patterns. The labelling with each tracer was either performed by thoroughly mixing it into the food before cooking, or alternatively by surface labelling after the food had been cooked. For the 99mTc-Sn-colloid tracer no difference was found in the measured gastric emptying times resulting from either pre-cooking labelling or surface labelling of the meals. Cooking the tracer together with the ingredients does however seem to promote a firm entrapment of the 111In-polymer beads into a solid protein, and in this manner the 111In-labelled resin appears to be a reliable solid food tracer. Surface labelling with 111In-polymer beads of a solid meal with a smooth texture fails totally and the tracer empties with the liquid phase.

The use of autologous 111In-labelled platelets and scintigraphy to illustrate enhanced platelet activity during erection in the chacma baboon.

The demonstration of thrombelastographic hypercoagulability in the penile blood during erection, and the accompanying deposition of fibrin onto the endothelial layer of the deep penile artery and trabecular surface inspired this investigation of the possible role that platelets might play in the process. The bloodpooling pattern in the penis during and after erection from electro-stimulation was studied in 9 male adult baboons (Papio ursinus) using in vivo 99mTc-labelled red blood cells and scintigraphy. Platelet activity was similarly investigated after administering autologous 111In-labelled platelets to the baboons. The results indicate an enhanced platelet concentration with respect to bloodpooling during erection, and an entrapment of platelets after erection.

Scintigraphic phase analysis of abnormal A-V conduction in a baboon.

During an interventional cardiac investigation on an anaesthetised baboon (Papio ursinus) the animal developed A-V block. Scintigraphic phase analysis leading to quantified intraventricular delays and histogram characteristics pointed to abnormalities which persisted even after A-V block was replaced by nodal tachycardia as was reflected by the electrocardiogram. This indicated towards an increased diagnostic sensitivity with the use of phase analytical methods.

Detection of abscesses and lymphosarcoma with 111In-deferoxamine mesylate.

Indium-111 deferoxamine was used to delineate induced abscesses or different ages in a baboon, and lymph nodes in a case of canine spontaneous lymphosarcoma, by means of gamma-scintigraphy. Positive results were obtained already 1 hr after administration of the scanning agent, and the lesion-to-background ratio improved progressively with time. The tissue distribution of the radiopharmaceutical was determined in rats, and showed a relatively high isotope retention in the kidneys.

Drug effects on cerebral blood flow in the baboon model--acetazolamide and nimodipine.

The sensitivity of the baboon model under anaesthesia for single photon emission computed tomography (SPECT) of the brain with 99mTc-HMPAO, as recently developed by us to study cerebral blood flow patterns, was investigated using drugs that are known to increase cerebral blood flow, e.g. acetazolamide, the carbonic anhydrase inhibitor and nimodipine, the calcium channel blocker. Increases in cerebral blood flow for both acetazolamide and nimodipine were observed that correspond well with other studies. Statistically significant regional specificity was noted for acetazolamide and nimodipine. Interestingly a combination of these drugs did not enhance cerebral blood flow but rather decreased it in comparison with the individual drug responses. The results were correlated with arterial blood pressure, heart rate, pCO2 and pO2. A blood pressure decrease was noted for both drugs, while acetazolamide had a marked influence on pO2. The results indicate that the baboon model is sensitive for evaluation of drug effects on cerebral blood flow.

The sensitivity of radionuclide and thermodilution techniques to detect cardiac dysfunction in the baboon model during prolonged anaesthesia.

This study was undertaken to evaluate the fluctuations of cardiac parameters in a baboon model during pentobarbitone anaesthesia which will serve as a baseline control for shock studies. Thermodilution and radionuclide methods were used to determine cardiac parameters. Radionuclide studies were repeated without any cardiac catheters to assess the effect of these on cardiac performance. The results represent baseline fluctuations in cardiac parameters against which cardiac dysfunction can be diagnosed in shock studies. The results also indicate that cardiac catheterisation does not affect cardiac performance significantly.

Gated blood pool SPECT and phase analysis to assess simulated Wolff-Parkinson-White syndrome in the baboon.

This study assesses the diagnostic potential of a tomographic technique with phase analysis to detect premature electroventricular contraction patterns simulated by pacing in the baboon. The data of gated SPECT were analysed by backprojection of the Fourier coefficients, followed by angulation and integration to thick slices of the entire ventricular mass yielding separate ventricular contraction patterns in three perpendicular views. Electrodes were implanted in each baboon: at the sinoatrial node; posterior, left ventricular; anterior left ventricular; on the left and the right lateral ventricular walls. The atrium was stimulated throughout at a fixed rate. Subsequent ventricular stimuli followed during the QRS complex, such to invoke the appearance of pre-excitation QRS morphology. The first points of activation (FPA) from this algorithm were correctly detected for the RV, for the anterior and posterior sites, although the latter two manifested first points in the RV. LV pacing manifested also as a FPA in the RV, but was followed by a true subsequent point in the LV.

Biodistribution and accumulation in inflammatory lesions of different thiol reduction-mediated 99Tcm-IgG preparations in baboon models.

The diagnostic efficacy of 99Tcm-labelled non-specific polyclonal immunoglobulin (IgG) as tracer for abdominal inflammatory lesions is impeded by its unfavourable physiological organ distribution patterns. Modifications to the IgG molecules during preparation and labelling may alter its in vivo behaviour and accumulation in inflammatory foci. This report describes scintigraphic biodistribution studies in the baboon (normal and with inflammatory lesions) of various thiol reduction-mediated 99Tcm-IgG preparations. These are human IgG (Sandoglobulin) where the Fc-mediated complement activity is impaired, human IgG (Gammagard) where the Fc portion is left intact, and baboon IgG isolated from the serum of each animal (autologous): the first two preparations are commercially available. Normal baboon organ distributions were obtained for each tracer over a period of 3 h, commencing 4 h after administration. Similarly, lesion-to-background ratios in thigh and abdominal lesions (bacterial and chemical) were compared. Mean normal organ distributions (n = 6) were relatively constant during this period. Kidney uptake with IgG (Sandoglobulin) was significantly enhanced, as was liver uptake with IgG (Gammagard) and the baboon IgG. Biodistribution pattern changes after lesion induction tended to be similar for IgG (Gammagard) and baboon IgG, where activity washout became more prominent. Lesion-to-background ratios in the thigh far exceeded those in the abdomen, except for the individual animal's own IgG which performed well in this case.

Dose response from pharmacological interventions for CBF changes in a baboon model using 99Tcm-HMPAO and SPECT.

This study assesses the sensitivity of the baboon model under anaesthesia to determine by single photon emission computed tomography (SPECT) and 99Tcm-hexamethylpropyleneamine oxime (HMPAO) dose responses from drugs (acetazolamide) with known regional cerebral blood flow (rCBF) effects on humans. Three dosages of acetazolamide were chosen: 250, 500 and 750 mg. The effects of these were studied by conventional SPECT 5 min after intravenous (i.v.) administration and compared to previous studies of rCBF with the baboons under anaesthesia only. An additional study concerned the effect of 500 mg acetazolamide at 15 min after administration. Haemodynamic parameters and blood gases were also monitored. No statistically significant regional effects were noted (P > 0.05). The largest increase in CBF (39%) was observed from 500 mg acetazolamide after 5 min. This was statistically significantly different from control values only at a 10% level of confidence; then followed a 27% increase above control values after 750 mg (5 min). At 15 min 500 mg yielded values lower by 10% than the high dose. No effects were observed from 250 mg acetazolamide; only pO2 showed changes which largely confirm the CBF findings. The model did not give significant results at a 5% level of confidence but large fluctuations were observed, also in the haemodynamic and blood gas values. At a 10% level a significant dose response was confirmed for acetazolamide.