Intramuscular injection of 125I-botulinum neurotoxin-complex versus 125I-botulinum-free neurotoxin: time course of tissue distribution

Tang-Liu, Diane; Aoki, K. Roger; Dolly, J. Oliver; Paiva, Anton de; Houchen, T. L.; Chasseaud, L. F.; Webber, Colin E.

doi:10.1016/s0041-0101(03)00196-x

Cited by 95 publications

(60 citation statements)

References 13 publications

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“…Botulinum toxin acts at the picogram level in rats. In order to detect the toxins directly in vivo, 125 I-labeled toxins would be required since otherwise a high dose exceeding the lethal dose would have to be used (26). However, we used a non-isotope-requiring method in this study that had been reported to be the most sensitive test to monitor the presence of active toxins in vivo, because a single toxin molecule can proteolyse a large number of SNAP-25 target molecules, providing a dramatic amplifying effect (16).…”

Section: Discussionmentioning

confidence: 99%

Type A1 but Not Type A2 Botulinum Toxin Decreases the Grip Strength of the Contralateral Foreleg Through Axonal Transport From the Toxin-Treated Foreleg of Rats

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Type A1 but Not Type A2 Botulinum Toxin Decreases the Grip Strength of the Contralateral Foreleg Through Axonal Transport From the Toxin-Treated Foreleg of Rats

et al. 2011

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“…Upon intramuscular injection, Botox (serotype A) action is primarily local, with minimal diffusion to other tissues [41]. Acutely, muscle electrical activity is reduced within hours of IM injection and site specific muscle contractions are nearly completely inhibited by 18 h [6].…”

Section: Discussionmentioning

confidence: 99%

Botox induced muscle paralysis rapidly degrades bone

Warner

Sanford

Becker

et al. 2006

Bone

180

193

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The means by which muscle function modulates bone homeostasis is poorly understood. To begin to address this issue, we have developed a novel murine model of unilateral transient hindlimb muscle paralysis using botulinum toxin A (Botox). Female C57BL/6 mice (16 weeks) received IM injections of either saline or Botox (n = 10 each) in both the quadriceps and calf muscles of the right hindleg. Gait dysfunction was assessed by multi-observer inventory, muscle alterations were determined by wet mass, and bone alterations were assessed by micro-CT imaging at the distal femur, proximal tibia, and tibia mid-diaphysis. Profound degradation of both muscle and bone was observed within 21 days despite significant restoration of weight bearing function by 14 days. The muscle mass of the injected quadriceps and calf muscles was diminished −47.3% and −59.7%, respectively, vs. saline mice (both P < 0.001). The ratio of bone volume to tissue volume (BV/TV) within the distal femoral epiphysis and proximal tibial metaphysis of Botox injected limbs was reduced −43.2% and −54.3%, respectively, while tibia cortical bone volume was reduced −14.6% (all P < 0.001). Comparison of the contralateral non-injected limbs indicated the presence of moderate systemic effects in the model that were most probably associated with diminished activity following muscle paralysis. Taken as a whole, the micro-CT data implied that trabecular and cortical bone loss was primarily achieved by bone resorption. These data confirm the decisive role of neuromuscular function in mediating bone homeostasis and establish a model with unique potential to explore the mechanisms underlying this relation. Given the rapidly expanding use of neuromuscular inhibitors for indications such as pain reduction, these data also raise the critical need to monitor bone loss in these patients.

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“…This observation is consistent with the diffusion of BoNT-A in tissues. It was previously shown, using radiolabeled BoNT-A in animal models, that the toxin remains in the tissue injected, diffusing over a depth of 7 mm from the injection site (28). This diffusion is even larger in humans when using larger volumes for the injection (29).…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin potentiates cancer radiotherapy and chemotherapy.

Ansiaux

Baudelet

Cron

et al. 2006

Clinical Cancer Research

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Purpose: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments.To increase the efficacy of anticancer treatments, efforts must be made to find new strategies for transiently opening the tumor vascular bed to alleviate tumor hypoxia (source of resistance to radiotherapy) and improve the delivery of chemotherapeutic agents. We hypothesized that Botulinum neurotoxin type A (BoNT-A) could interfere with neurotransmitter release at the perivascular sympathetic varicosities, leading to inhibition of the neurogenic contractions of tumor vessels and therefore improving tumor perfusion and oxygenation. Experimental Design: To test this hypothesis, BoNT-A was injected locally into mouse tumors (fibrosarcoma FSaII, hepatocarcinoma transplantable liver tumor), and electron paramagnetic resonance oximetry was used to monitor pO 2 in vivo repeatedly for 4 days. Additionally, contrast-enhanced magnetic resonance imaging was used to measure tumor perfusion in vivo. Finally, isolated arteries were mounted in wire myograph to monitor specifically the neurogenic tone developed by arterioles that were co-opted by the surrounding growing tumor cells. Results: Using these tumor models, we showed that local administration of BoNT-A (two sites; dose, 29 units/kg) substantially increases tumor oxygenation and perfusion, leading to a substantial improvement in the tumor response to radiotherapy (20 Gy of 250-kV radiation) and chemotherapy (cyclophosphamide, 50 mg/kg). This observed therapeutic gain results from an opening of the tumor vascular bed by BoNT-A because we showed that BoNT-A could inhibit neurogenic tone in the tumor vasculature. Conclusions: The opening of the vascular bed induced by BoNT-A offers a way to significantly increase the response of tumors to radiotherapy and chemotherapy.

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Intramuscular injection of 125I-botulinum neurotoxin-complex versus 125I-botulinum-free neurotoxin: time course of tissue distribution

Cited by 95 publications

References 13 publications

Type A1 but Not Type A2 Botulinum Toxin Decreases the Grip Strength of the Contralateral Foreleg Through Axonal Transport From the Toxin-Treated Foreleg of Rats

Type A1 but Not Type A2 Botulinum Toxin Decreases the Grip Strength of the Contralateral Foreleg Through Axonal Transport From the Toxin-Treated Foreleg of Rats

Botox induced muscle paralysis rapidly degrades bone

Botulinum toxin potentiates cancer radiotherapy and chemotherapy.

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