The Role of F-Fluorodeoxyglucose (FDG) Positron Emission Tomography–Computed Tomography (PET/CT) in the Screening of Cervical Cancer: A Literature Review

F-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) has of late gained prominence in the investigation of cervical cancer since it gives a better clarity on imaging modalities for the status of the lymph node and distant metastasis. The current review is an appraisal of the recent updates on the role of FDG-PET/CT in the screening of cervical cancer as evidenced by publications till date. 985 studies were obtained in the initial search on cervical cancer and publications selected based on inclusion and exclusion criteria. In the final selection, 14 were selected and coded as the most appropriate for the present review. Valuable studies on (FDG) PET/CT have been identified. These studies point to the fact that recent advanced protocols like PET/CT supported by therapeutic innovations ensure better cancer care and survival chances in cervical cancer patients.     

Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta) at the California National Primate Research Center (1992–2014)

Necropsy records and associated clinical histories from the rhesus macaque colony at the California National Primate Research Center were reviewed to identify mortality related to cardiac abnormalities involving left ventricular hypertrophy (LVH). Over a 21-y period, 162 cases (female, 90; male, 72) of idiopathic LVH were identified. Macaques presented to necropsy with prominent concentric hypertrophy of the left ventricle associated with striking reduction of the ventricular lumen. Among all LVH cases, 74 macaques (female, 39; male, 35), mostly young adults, presented for spontaneous (sudden) death; more than 50% of these 74 cases were associated with a recent history of sedation or intraspecific aggression. The risk of sudden death in the 6- to 9-y-old age group was significantly higher in male macaques. Subtle histologic cardiac lesions included karyomegaly and increased cardiac myocyte diameter. Pedigree analyses based on rhesus macaque LVH probands suggested a strong genetic predisposition for the condition. In humans, hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, associated with diverse clinical outcomes ranging from asymptomatic disease to sudden death. Although the overall risk of disease complications such as sudden death, end-stage heart failure, and stroke is low (1% to 2%) in patients with HCM, the absolute risk can vary dramatically. Prima facie comparison of HCM and LVH suggest that further study may allow the development of spontaneously occurring LVH in rhesus macaques as a useful model of HCM, to better understand the pathogenesis of this remarkably heterogeneous disease.Abbreviations: HCM, hypertrophic cardiomyopathy; LVH, left ventricular hypertrophyNaturally occurring hypertrophic cardiomyopathy (HCM) has been recognized in a variety of species including pigs,¹³ cats^18,32 and humans. HCM emerged as an accepted clinical entity in humans during the late 1950s, with the publication of 2 key papers.^5,46 Since then, a vast, complex, and sometimes contradictory body of research has developed around this clinically, phenotypically, and genotypically heterogeneous disease. HCM is defined as left ventricular hypertrophy without chamber dilation in the absence of either a systemic or other cardiac disease that would result in pressure overload and compensatory hypertrophy.^22,39 The primary physiologic abnormality in HCM is reduced stroke volume due to impaired diastolic filling, which is secondary to reduced chamber size and impaired relaxation of the left ventricular myocardium during diastole; this impaired relaxation is due to the reduced compliance or increased stiffness of the hypertrophied left ventricle.⁴⁹Phenotypically, hearts affected by HCM exhibit a wide variety of changes summarized as left ventricular hypertrophy, which may be symmetric or asymmetric and which results in reduced left ventricular lumen volume, reduced stroke volume, and typically increased ejection fraction. These changes can be accompanied by valvular changes, some of which can be obstructive. Small intramural coronary arteries may have thickened walls and narrowed lumens due to proliferation of smooth muscle cells and collagen.³⁰ Histologic changes in the left ventricle associated with—but not prerequisite for—HCM include myocyte hypertrophy and disarray, nuclear atypia, and expansion of the interstitial collagen compartment.^14,22In the 1980s, growing recognition that HCM was familial directed efforts toward identifying a genetic defect. Primary HCM in humans has been identified as an autosomal dominant disease with variable penetrance and a remarkable diversity in clinical presentation and disease course.^27,40 The first mutation associated with HCM was a missense mutation in the gene encoding the β-myosin heavy chain.¹¹ More than 2 decades of subsequent investigation has demonstrated the extensive heterogeneity of the HCM phenotype, with at least 11 causative genes and more than 1400 mutations identified. These genes primarily encode thick and thin myofilament proteins of the sarcomere or Z disc (sarcomere structural proteins). The majority of mutations occur in 3 genes—β-myosin heavy chain, myosin-binding protein C, and troponin T—whereas other genes, including troponin I, α-tropomyosin and α-actin, account for a smaller proportion of patients.²² Mutations in several additional sarcomere and calcium-handling genes have been proposed but with less evidence to support pathogenicity. At present, the precise mutation does not alter management. However, adverse outcomes (sudden death, stroke, progressive symptoms) are more prominent in patients with sarcomere mutations than in those without an identifiable mutation.³⁷In other animal species, naturally occurring familial HCM has been best characterized in cats. Maine coon cats¹⁸ and ragdoll cats³² develop HCM that is strongly similar to the human disease in clinical presentation and histopathology. Similar to humans, HCM in cats is inherited as an autosomal dominant trait, with the responsible gene, the cardiac myosin-binding protein C gene, recently identified.^32,33 In addition, a genetically manipulated model has been developed in rabbits,²¹ as well as a vast array of mouse models.^1,7,45The purposes of this report were: 1) to identify cases of LVH diagnosed at necropsy in the rhesus macaque colony at the California National Primate Research Center since 1992; 2) to provide a preliminary pathologic characterization of these cases; and 3) to compare and contrast rhesus LVH and human HCM to assess the extent to which LVH might be developed as a model of HCM in a species closely related to humans.     

Can Gender Differences Be Evaluated in a Rhesus Macaque (Macaca mulatta) Model of Focal Cerebral Ischemia?

Gender differences, sex steroid effects, and sex-specific candidate therapeutics in ischemic stroke have been studied in rodents but not in nonhuman primates. In this feasibility study (n = 3 per group), we developed a model of transient focal cerebral ischemia in adult male and female rhesus macaques that consistently includes white matter injury. The animals also were used to determine whether gender-linked differences in histopathologic outcomes could be evaluated in this model in future, larger preclinical trials. Histologic brain pathology was evaluated at 4 d after 90 min of reversible occlusion of the middle cerebral artery (MCA). MCA occlusion was accomplished by using a transorbital approach and temporary placement of an aneurysm clip. Male and female rhesus macaques 7 to 11 y of age were studied. Baseline and intraischemic blood glucose, systolic blood pressure, heart rate, oxygen saturation, end-tidal CO₂, and rectal temperatures were not different among groups. The variability in injury volume was comparable to that observed in human focal cerebrovascular ischemia and in other nonhuman primate models using proximal MCA occlusion. In this small sample, the volume of injury was not different between male and female subjects, but observed variability was higher in female caudate nucleus, putamen, and hemisphere. This report is the first to compare cerebral ischemic outcomes in female and male rhesus macaques. The female rhesus macaque ischemic stroke model could be used after rodent studies to provide preclinical data for clinical trials in women.Abbreviations: BP, blood pressure; EtCO₂, end-tidal CO₂; MCA, middle cerebral artery; SpO₂, oxygen saturation of peripheral bloodStroke is defined as the symptomatic loss or alteration of bodily function that results from an insufficient supply of blood to part of the brain. The most common type of stroke is ischemic stroke, which accounts for 87% of stroke cases.¹ Ischemic stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities.^1,25,38 This sexually dimorphic epidemiology is present in childhood¹⁰ until late in life, well beyond the menopausal years.^13,31 These observations suggest that the presence of female sex steroids may not completely explain stroke''s sexual dimorphism.One of the new concepts that must be considered in stroke research is that therapies and treatments for this disease operate in different genetic landscapes in women and men. Consequently, any prospective neuroprotective or injurious compound may act differently in female and male ischemic brains. For example, the Women''s Health Study recently evaluated aspirin use over 10 y for primary prevention of cardiovascular events, including stroke, and in reduction of mortality from cardiovascular causes.³⁰ Aspirin lowered ischemic stroke risk by 24% in healthy women, in contrast to results from the men-only Physicians Health study,²⁷ in which aspirin had no effect on stroke in men. These differences in how women compared with men respond to candidate agents potentially could influence clinical trial outcomes.Ischemic stroke models have been developed and characterized in many animal species,¹⁴ including several nonhuman primate species like baboons, macaques, marmosets, and squirrel monkeys.^9,26 There are several advantages to using nonhuman primate ischemic stroke models. First, the neuroanatomy and cerebrovascular anatomy of nonhuman primates is highly similar to that in humans. For example, rodents have lissencephalic brains, whereas humans and many nonhuman primate species have gyrencephalic brains.⁹ Moreover, the striatal gray matter of rats and mice is interleaved with white matter, whereas the white matter tracts of nonhuman primates are organized predominantly in the internal capsule.⁹ This arrangement in nonhuman primates ensures homogeneity of tissue and microvascular architecture with that of humans. Second, there are well known and often paradoxical differences between hemostatic and vascular mechanisms in rodents and rabbits and in their responses to antithrombotic and fibrinolytic agents compared with those of humans.⁹ However, several nonhuman primate species show close analogy to human hemostatic and coagulation systems. Finally, nonhuman primate models demonstrate a close similarity to human cerebral embolism without the effect of thrombus on the ischemic territory; lower animal species frequently lack this trait.⁹Most focal ischemic stroke models in nonhuman primates involve occlusion of a single artery, such as the middle cerebral artery (MCA).^9,14 Vascular clipping, use of an extrinsic balloon device or snare ligature, electrocoagulation or photocoagulation, and embolization by means of an interventional approach are common methods to induce MCA occlusion in nonhuman primates.⁹ In an MCA occlusion model, the degree and distribution of blood flow depends on the duration of occlusion (transient occlusion for minutes to hours with or without reperfusion compared with permanent occlusion for hours to days with no reperfusion), site of occlusion along the MCA (proximal versus distal part of the artery), and the amount of collateral blood flow into the MCA territory.^9,14The study of gender differences, effects of sex steroids, and sex-specific candidate therapeutics in experimental stroke has been limited primarily to rodent models.²⁵ These issues have not been addressed directly in nonhuman primate models, because many stroke studies involving nonhuman primate subjects reported use of male animals only,^{6,7,16,18,20,22,33,40} did not indicate the gender of animals used,^{5,15,17,21,42,44,45} or did not stratify outcomes with respect to sex.^12,23 The lack of data from female animals of higher-order species severely limits the translation of experimental data to women requiring treatment for stroke or neuroprotection during stroke. Similarly, the lack of suitably controlled preclinical data in both sexes of higher-order species potentially can lead to poorly designed clinical trials or failure of clinical trials when an agent or therapy of interest may have real benefit (or lack thereof) in a single gender. Nonhuman primate models could be invaluable in stroke studies of gender differences, the response to therapeutics in each gender, and the perimenopausal state. These models might serve as a useful bridge between experimental gender-based studies in rodents and the design of clinical trials in humans, because female nonhuman primate species such as the rhesus macaque have menstrual cycles and hormonal responses analogous to those of female humans.²We present here the results of a feasibility study in which we developed a model of transient focal cerebral ischemia in male and female rhesus macaques (Macaca mulatta) that would consistently include white matter injury. We also examined whether gender differences in histopathologic outcomes might be evaluated in this model in future, larger experimental trials examining the response to potential new stroke therapeutics initially screened and identified in rodent studies.     

Does 18F-FDG Positron Emission Tomography-Computed Tomography Have a Role in Initial Staging of Hepatocellular Carcinoma?

Background and Aim

The utility of fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography-computed tomography (PET/CT) in initial staging of hepatocellular carcinoma (HCC) has yet to be fully explored. We assessed the usefulness of ¹⁸F-FDG PET/CT in initial staging of HCC.

Methods

A total of 457 consecutive patients initially diagnosed with HCC at Seoul National University Hospital between 2006 and 2012 were evaluated retrospectively to assess the impact of ¹⁸F-FDG PET/CT on staging and compliancy with Milan criteria, relative to dynamic CT of liver and chest x-ray.

Results

Seven among the 457 patients studied showed a shift in Barcelona Clinic Liver Cancer [BCLC] stage (A→C: 6 patients; B→C: 1 patient) and 5 patients who had originally met Milan criteria no longer qualified. ¹⁸F-FDG PET/CT had value in initial staging of early (stage A) or intermediate (stage B) HCC, as determined by dynamic CT of liver and BCLC or AJCC classifications, whereas BCLC stage 0 and stage C tumors were unchanged (P<0.001). ¹⁸F-FDG PET/CT disclosed additional metastases in patients with American Joint Committee on Cancer [AJCC] T2 (2.7%), T3a (5.3%), and T3b (4.8%) classifications.

Conclusions

In initial staging of HCC, ¹⁸F-FDG PET/CT provided additional information, impacting the patients with BCLC (stages A and B) and AJCC (T2 and T3) classifications. Its use might be thus appropriate for these patient subsets, especially if hepatic resection or liver transplantation is planned.     

Can Positron Emission Tomography/Computed Tomography with the Dual Tracers Fluorine-18 Fluoroestradiol and Fluorodeoxyglucose Predict Neoadjuvant Chemotherapy Response of Breast Cancer? ----A Pilot Study

Objective

To assess the clinical value of dual tracers Positron emission tomography/computed tomography (PET/CT) ¹⁸F-fluoroestradiol (¹⁸F-FES) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in predicting neoadjuvant chemotherapy response (NAC) of breast cancer.

Methods

Eighteen consecutive patients with newly diagnosed, non-inflammatory, stage II and III breast cancer undergoing NAC were included. Before chemotherapy, they underwent both ¹⁸F-FES and ¹⁸F-FDG PET/CT scans. Surgery was performed after three to six cycles of chemotherapy. Tumor response was graded and divided into two groups: the responders and non-responders. We used the maximum standardized uptake value (SUVmax) to qualify each primary lesion.

Results

Pathologic analysis revealed 10 patients were responders while the other 8 patients were non-responders. There was no statistical difference of SUVmax-FDG and tumor size between these two groups (P>0.05). On the contrary, SUVmax-FES was lower in responders (1.75±0.66 versus 4.42±1.14; U=5, P=0.002); and SUVmax-FES/FDG also showed great value in predicting outcome (0.16±0.06 versus 0.54±0.22; U=5, P=0.002).

Conclusions

Our study showed ¹⁸F-FES PET/CT might be feasible to predict response of NAC. However, whether the use of dual tracers ¹⁸F-FES and ¹⁸F-FDG has complementary value should be further studied.     

Whom to Groom and for What? Patterns of Grooming in Female Barbary Macaques (Macaca sylvanus)

Grooming is one of the most conspicuous social interactions among nonhuman primates. The selection of grooming partners can provide important clues about factors relevant for the distribution of grooming within a social group. We analyzed grooming behavior among 17 semi-free ranging female Barbary macaques (Macaca sylvanus). We tested whether grooming is related to kinship, rank and friendship. Furthermore, we tested whether grooming is reciprocated or exchanged for rank related benefits (i.e. lower aggression and increased tolerance whilst feeding). We found that in general grooming was reciprocally exchanged, directed up the hierarchy and at the same time affected by friendship and kinship. Grooming was more frequent among individuals with higher friendship values as well as amongst related individuals. We also divided our data set on the basis of rank difference and tested if different power asymmetries between individuals affected the tendency to exchange grooming for rank related benefits and grooming reciprocation. In support of our initial hypothesis our results show that the reciprocation of grooming was a significant predictor of grooming interactions between individuals of similar rank, but not between those individuals more distantly separated in the social hierarchy. However, we did not find any evidence for grooming being exchanged for rank related benefits in either data set. Our results, together with previously published studies, illustrate the behavioral flexibility of macaques. It is clear that multiple studies of the same species are necessary to gather the data required for the solid comparative studies needed to shed light on patterns of grooming behavior in primates.     

The Effect of Dominance Rank on the Distribution of Different Types of Male–Infant–Male Interactions in Barbary Macaques (Macaca sylvanus)

International Journal of Primatology - In several cercopithecine species males exhibit a specific type of male–infant–male interaction during which two males briefly manipulate an...     

Early Detection of Erlotinib Treatment Response in NSCLC by 3′-Deoxy-3′-[18F]-Fluoro-L-Thymidine ([18F]FLT) Positron Emission Tomography (PET)

Background

Inhibition of the epidermal growth factor receptor (EGFR) has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). Somatic mutations of EGFR were found in lung adenocarcinoma that lead to exquisite dependency on EGFR signaling; thus patients with EGFR-mutant tumors are at high chance of response to EGFR inhibitors. However, imaging approaches affording early identification of tumor response in EGFR-dependent carcinomas have so far been lacking.

Methodology/Principal Findings

We performed a systematic comparison of 3′-Deoxy-3′-[¹⁸F]-fluoro-L-thymidine ([¹⁸F]FLT) and 2-[¹⁸F]-fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) positron emission tomography (PET) for their potential to identify response to EGFR inhibitors in a model of EGFR-dependent lung cancer early after treatment initiation. While erlotinib-sensitive tumors exhibited a striking and reproducible decrease in [¹⁸F]FLT uptake after only two days of treatment, [¹⁸F]FDG PET based imaging revealed no consistent reduction in tumor glucose uptake. In sensitive tumors, a decrease in [¹⁸F]FLT PET but not [¹⁸F]FDG PET uptake correlated with cell cycle arrest and induction of apoptosis. The reduction in [¹⁸F]FLT PET signal at day 2 translated into dramatic tumor shrinkage four days later. Furthermore, the specificity of our results is confirmed by the complete lack of [¹⁸F]FLT PET response of tumors expressing the T790M erlotinib resistance mutation of EGFR.

Conclusions

[¹⁸F]FLT PET enables robust identification of erlotinib response in EGFR-dependent tumors at a very early stage. [¹⁸F]FLT PET imaging may represent an appropriate method for early prediction of response to EGFR TKI treatment in patients with NSCLC.     

Longitudinal Assessment of Tau Pathology in Patients with Alzheimer’s Disease Using [18F]THK-5117 Positron Emission Tomography

The formation of neurofibrillary tangles is believed to contribute to the neurodegeneration observed in Alzheimer’s disease (AD). Postmortem studies have shown strong associations between the neurofibrillary pathology and both neuronal loss and the severity of cognitive impairment. However, the temporal changes in the neurofibrillary pathology and its association with the progression of the disease are not well understood. Tau positron emission tomography (PET) imaging is expected to be useful for the longitudinal assessment of neurofibrillary pathology in the living brain. Here, we performed a longitudinal PET study using the tau-selective PET tracer [¹⁸F]THK-5117 in patients with AD and in healthy control subjects. Annual changes in [¹⁸F]THK-5117 binding were significantly elevated in the middle and inferior temporal gyri and in the fusiform gyrus of patients with AD. Compared to patients with mild AD, patients with moderate AD showed greater changes in the tau load that were more widely distributed across the cortical regions. Furthermore, a significant correlation was observed between the annual changes in cognitive decline and regional [¹⁸F]THK-5117 binding. These results suggest that the cognitive decline observed in patients with AD is attributable to the progression of neurofibrillary pathology. Longitudinal assessment of tau pathology will contribute to the assessment of disease progression and treatment efficacy.     

Costs of and Investment in Mate-Guarding in Wild Long-Tailed Macaques (Macaca fascicularis): Influences of Female Characteristics and Male–Female Social Bonds

Male primates living in multimale groups tend to direct mate and mate-guarding choices toward females of high reproductive value, i.e., high-ranking, parous females, or females with which they share strong bonds. Little is known, however, about the constraints that may limit male mate-guarding choices (the costs of this behavior) and the influence of the females’ quality on male investment in mate-guarding. We aimed to study the effects of female rank, parity status, and male–female social bond strength on the costs of and investment in mate-guarding by males. We carried out our study during two reproductive seasons on three groups of wild long-tailed macaques in Indonesia. We combined behavioral observations on male locomotion and activity with noninvasive measurements of fecal glucocorticoids (fGC). Males spent less time feeding when mate-guarding nulliparous females than when mate-guarding parous females and tended to have higher fGC levels when mate-guarding low-ranking nulliparous females than when mate-guarding high-ranking nulliparous ones. Evolution should thus favor male choice for high-ranking parous females because such a decision brings benefits at proximate (reduced costs of mate-guarding) and ultimate (higher reproductive value) levels. Further, male investment in mate-guarding was flexible and contingent on female reproductive and social value. Males were more vigilant and more aggressive toward other males when mate-guarding females to which they were strongly bonded and/or high-ranking ones than when mate-guarding other females. Our findings bring a new dimension to the study of mate choice by showing that males not only mate preferentially with high-quality females but may also aim to secure paternity with these females through optimized monopolization.     

Noninvasive Visualization of the Activated αvβ3 Integrin in Cancer Patients by Positron Emission Tomography and [18F]Galacto-RGD

BackgroundThe integrin αvβ3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being studied to enable noninvasive determination of αvβ3 expression. We developed [¹⁸F]Galacto-RGD, a ¹⁸F-labeled glycosylated αvβ3 antagonist, allowing monitoring of αvβ3 expression with positron emission tomography (PET).ConclusionsMolecular imaging with [¹⁸F]Galacto-RGD and PET can provide important information for planning and monitoring anti-angiogenic therapies targeting the αvβ3 integrins and can reveal the involvement and role of this integrin in metastatic and angiogenic processes in various diseases.     

Molecular Simulation to Aid in the Understanding of the Aβ(1–42) Peptide of Alzheimer's Disease

Abstract

The Aβ(1–42) peptide of Alzheimer's disease was studied by molecular modeling. The coordinates of the peptide were experimentally generated from solution-NMR spectroscopy, and the conformations were energy minimized using a combination of connectivity-based iterative partial equalization of orbital electronegativity with the MM + force field.

There is a central folded domain in the Aβ peptide. This part is an apolar α-helix. The remaining residues form β-sheets. Aggregation requires that β-sheets interact by noncovalent bonding forces. The unsoluble, aggregated complexes are energetically stable and have ordered structures.

A perspective in drug research is to design compounds that inhibit the hydrophobic cores of the individual Aβ peptides, blocking so the associations between the β-strains.     

Functions of an unreported “rocking-embrace” gesture between female Japanese Macaques (Macaca fuscata) in Kinkazan Island,Japan

Recently, research has focused on the effects of the concurrence of multimodal signals and their efficacy and meaning. We observed an unreported behaviour, a ventro-ventral “rocking-embrace” gesture that is always accompanied by lip smacking as the facial expression and sometimes by a girney call, in wild Japanese macaques (Macaca fuscata) living in Kinkazan Island, northern Japan. This study examined the form and contexts of the occurrence of such multimodal signals in order to elucidate its functions. Eighty-eight cases of rocking embrace were recorded during 183 h of observation over 22 days. Adult females were involved in all of the cases. Of the 71 cases between adult females in which behaviours prior to the rocking embrace could be identified, 13 cases were allogrooming interruptions, 11 were aggression, and 42 were approaches, most of which occurred between non-kin grooming partners. The rocking embrace was often followed by allogrooming. This suggests that rocking embraces occur under stressful conditions and may function to reduce tensions. This conclusion is consistent with the contexts and functions of lip smacking and girneys shown in previous studies. In contrast with lip smacking and girneys, neither a rocking embrace nor a ventro-ventral embrace (without rocking) between anoestrous adult females has been previously shown in Japanese macaques. In other macaque species, however, the latter gesture is often observed as an affiliative behaviour that immediately follows conflict; it functions to reconcile or as a greeting when it occurs immediately after an approach. Rocking embraces among the Kinkazan macaques occur in contexts similar to, and have a similar function to, the ancestral gesture of ventro-ventral embracing (which is hidden in Japanese macaques) and the ancestral display of lip smacking (which is still observed in Japanese macaques). The ventro-ventral embrace as a tactile signal might have been hidden since it was made redundant by the visual signal of lip smacking in ancestral macaques.     

Male–Male Relationships in Lion-tailed Macaques (<Emphasis Type="Italic">Macaca silenus</Emphasis>) and Bonnet Macaques (<Emphasis Type="Italic">Macaca radiata</Emphasis>)

Socioecology suggests that female distribution in space is determined by the distribution of food resources and the male distribution is influenced by female distribution. Though studies have traditionally focused on females, males have received increasing attention in recent years. We compared male–male relationships in lion-tailed macaques and bonnet macaques. Because bonnet macaques have a high adult male:female sex ratio and are seasonal breeders whereas lion-tailed macaques have a low adult male:female sex ratio and are largely aseasonal breeders, we predicted that bonnet macaque males would be spatially and socially more tolerant of each other and would have less linear dominance relationships than lion-tailed macaques. We recorded male–male and male–female relationships in 1 group of wild macaques of each species via scan sampling and 1–0 sampling. The results revealed that lion-tailed macaque males largely remained at a distance from each other whereas bonnet macaque males remained in close proximity to one another. Lion-tailed macaque males were more agonistic toward each other whereas bonnet macaque males showed more affiliative interactions. The dominance hierarchy among lion-tailed macaque males was more linear than among bonnet macaque males. Our data support the hypothesis that the study of spatial structuring, temporality of interactions, and linearity of social relationships may contribute to a better understanding of macaque social systems.