Synthesis and Biodistribution of [11C]Adenosine 5′-Monophosphate ([11C]AMP)

Mathews, William B.; Nakamoto, Yuji; Abraham, Edward; Scheffel, Ursula; Hilton, John; Ravert, Hayden T.; Tatsumi, Mitsuaki; Rauseo, Paige; Traughber, Bryan; Salikhova, Anna Y.; Dannals, Robert F.; Wahl, Richard L.

doi:10.1007/s11307-005-4118-6

Cited by 14 publications

(16 citation statements)

References 12 publications

(8 reference statements)

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“…Rather, the radiotracer was found primarily in red blood cells and in two highly perfused organs, lung and heart. In the blood, the uptake of 5Ј-[ 11 C]AMP was observed to alter the ADP/ATP ratio, as predicted by the adenylate equilibrium (16). Our studies demonstrate that 5Ј-[ 14 C]AMP was taken up rapidly by erythrocytes from wild type and CD73 Ϫ/Ϫ mice.…”

Section: Discussionsupporting

confidence: 64%

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A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals

Daniels

Zhang

O’Brien

et al. 2010

Journal of Biological Chemistry

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Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5-AMP uptake by erythrocytes. Wild type, ecto-5-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5-AMP-induced hypometabolism in a similar fashion. Injection of 5-AMP leads to two distinct declining phases of oxygen consumption (VO 2 ). The phase I response displays a rapid and steep decline in VO 2 that is independent of body temperature (T b ) and ambient temperature (T a ). It is followed by a phase II decline that is linked to T b and moderated by T a . Altering the dosages of 5-AMP from 0.25-to 2-fold does not change the phase I response. For mice, a T a of 15°C is effective for induction of DH with the appropriate dose of 5-AMP. Erythrocyte uptake of 5-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5-AMP administration and is in parallel with the phase I decline in VO 2 . In summary, our investigations reveal that 5-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5-AMP. Mammals in deep hypometabolism (DH)5 with severe hypothermia and stupor are only observed naturally during hibernation (1). During hibernation, an animal's overall metabolic rate, based on oxygen consumption, is a small fraction of its euthermic needs. The biochemical event that triggers this hypometabolism is an enigma. It is thought that non-hibernating mammals cannot undertake a similar hypometabolic process because deep hypothermia is often associated with ventricular fibrillation and cardiac arrest.However, organs from non-hibernators can withstand a considerable ischemic period in a hypometabolic state. For example, during human organ transplantation, donated organs are transported in a cold ischemic state in the complete absence of blood circulation for many h (2), yet when implanted into a recipient, the restoration of blood flow and rewarming revives full organ function. This phenomenon also illustrates the important role of oxygen transportation by erythrocytes in metabolic activity. In addition, observations that exsanguination and prolonged hypoxia can result in hypothermia further demonstrate the importance of oxygen transportation and availability as factors that can modulate the metabolic rate in mammals (3, 4).We have demonstrated that the metabolite 5Ј-AMP can induce mice to undergo transient hypometabolism with T b as low as 26°C, similar to a torpor-like state (5). The T b of animals in torpor is defined to be at or moderately below 31°C (6). Here, we demonstrate tha...

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Section: Discussionsupporting

confidence: 64%

“…Previous studies have shown that 5Ј-[ 11 C]AMP cannot cross the blood brain barrier (16). Rather, the radiotracer was found primarily in red blood cells and in two highly perfused organs, lung and heart.…”

Section: Discussionmentioning

confidence: 95%

A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals

Daniels

Zhang

O’Brien

et al. 2010

Journal of Biological Chemistry

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“…The putative contention is that intraperitoneal administration of high 5'-AMP concentrations (e.g., 500 mg/kg) lead to extensive 5'-AMP uptake by erythrocytes [79], after which the high intracellular levels of 5'-AMP drive the adenylate equilibrium (ATP + AMP  2 ADP) towards production of ADP, thereby depleting erythrocyte ATP levels [76,77]. As a result, erythrocyte 2,3-disphosphoglycerate is upregulated, limiting the binding of oxygen to hemoglobin's oxygen binding sites (referred to as oxygen affinity hypoxia) [76].…”

Section: Adenosine Monophosphatementioning

confidence: 99%

The physiology of artificial hibernation

Heger

2015

JCTRes

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Incomplete understanding of the mechanisms responsible for induction of hibernation prevent translation of natural hibernation to its artificial counterpart. To facilitate this translation, a model was developed that identifies the necessary physiological changes for induction of artificial hibernation. This model encompasses six essential components: metabolism (anabolism and catabolism), body temperature, thermoneutral zone, substrate, ambient temperature, and hibernation-inducing agents. The individual components are interrelated and collectively govern the induction and sustenance of a hypometabolic state. To illustrate the potential validity of this model, various pharmacological agents (hibernation induction trigger, delta-opioid, hydrogen sulfide, 5'-adenosine monophosphate, thyronamine, 2-deoxyglucose, magnesium) are described in terms of their influence on specific components of the model and corollary effects on metabolism. Relevance for patients: The ultimate purpose of this model is to help expand the paradigm regarding the mechanisms of hibernation from a physiological perspective and to assist in translating this natural phenomenon to the clinical setting.

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“…E-mail: ahorti1@jhmi.edu variety of disorders including cancer, cystic fibrosis, diabetes and cardiac disease. 15 There are currently several radiotracers synthesized having potential for PET imaging of adenylate metabolism (see the latest references in the paper by Mathew et al 16 ). Nevertheless, a radiotracer with better imaging properties is needed.…”

Section: If Radiolabeled With [mentioning

confidence: 99%

Synthesis of 2-[18F]fluoroadenosine (2-[18F]FAD) as potential radiotracer for studying malignancies by PET

Horti

Ravert

Mathews

et al. 2006

J Label Compd Radiopharm

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18 F]FAD), a potential radioligand for assessment of adenylate metabolism, was synthesized by carrier-added and no-carrier-added procedures via nucleophilic radiofluorination of 2-fluoroadenosine and 2-iodoadenosine. The radiochemical yield, specific radioactivity and radiochemical purity of carrier-added and no-carrier-added 2-[ 18 F]FAD were 5%, 22-30 mCi/mmol and 99%, and 0.5%, 1200-1700 mCi/mmol and 99%, respectively.

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Synthesis and Biodistribution of [11C]Adenosine 5′-Monophosphate ([11C]AMP)

Cited by 14 publications

References 12 publications

A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals

A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals

The physiology of artificial hibernation

Synthesis of 2-[18F]fluoroadenosine (2-[18F]FAD) as potential radiotracer for studying malignancies by PET

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