PET/CT Imaging of I-124–Radiolabeled Bevacizumab and Ranibizumab after Intravitreal Injection in a Rabbit Model

Christoforidis, John B.; Carlton, Michelle M.; Knopp, Michael V.; Hinkle, George H.

doi:10.1167/iovs.10-6862

Cited by 53 publications

(39 citation statements)

References 18 publications

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“…This approach reduces the number of animals, but reliable recovery estimates are needed in the determination of the drug yield (Duvvuri et al, 2003) and the duration of the experiments is often limited. In some cases, a radioactively labeled drug has been injected to the vitreous followed by imaging with positron emission tomography (Christoforidis et al, 2011(Christoforidis et al, , 2012. In all cases, the sampling times are crucial for obtaining reliable pharmacokinetic profiles and parameter values.…”

Section: Design Of An Intravitreal Pharmacokinetic Studymentioning

confidence: 99%

“…fluconazole; vitreal clearance 0.753 ml/h (Gupta et al, 2000)), whereas elimination of large and hydrophilic compounds is restricted to the anterior route (e.g. bevacizumab; vitreal clearance 0.019 ml/h (Bakri et al, 2007;Christoforidis et al, 2011;del Amo et al, 2015)). These processes determine drug elimination in rabbit and human eyes and it is described as intravitreal clearance.…”

Section: Introductionmentioning

confidence: 99%

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Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

Amo

Urtti

2015

Experimental Eye Research

182

136

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Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics.

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Section: Design Of An Intravitreal Pharmacokinetic Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

Amo

Urtti

2015

Experimental Eye Research

182

136

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“…These enhancements will continue to improve the sensitivity, precision, and quantitative accuracy of measured organ perfusion rates, cell survival, and proliferation rates obtained by small-animal PET. Several articles have hinted the potential application of 18F-FDG microPET-CT in clinical research. Christoforidis et al (13) performed intravitreal injection with I-124 bevacizumab and ranibizumab in rabbit model to determine whether bevacizumab and ranibizumab remain confined within the vitreous cavity after intravitreal injection and to determine the pharmacokinetic properties of these agents within the vitreous cavity, evaluating by a microPET-CT scanning. Park et al (14) used microPET-CT to assess a novel low-dose radiotherapy regimen for treating glioblastoma multiforme.…”

Section: Discussionmentioning

confidence: 99%

MicroPET-CT evaluation of interstitial brachytherapy in pancreatic carcinoma xenografts

Wang

Chen

et al. 2013

Acta Radiol

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“…In another study Christoforidis et al were defined that there was no significant escape of bevacizumab and ranibizumab from the vitreous cavity after intravitreal injection 33 . This period in primates is 6.9 days for bevacizumab and 3.5 days for ranibizumab.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Corneal Neovascularization by Subconjunctival Injection of Ranibizumab and Bevacizumab in Rabbit Cornea

Ekinci¹,

Çağatay²,

Yazar³

et al. 2013

Kafkas Univ Vet Fak Derg

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The aim of this study was to evaluate the effects of subconjunctival ranibizumab and bevacizumab injection on angiogenesis in the rabbit cornea. The corneas of 24 New Zealand rabbits were cauterized with silver nitrate to induce neovascularization. The eyes were irrigated with 10 ml of 0.9% saline solution. The alkaline burns were similar in all the rabbits. At the 24 h after cauterization, the rabbits were divided into three groups of eight animals each: The first group (GC) received 0.02 ml 0.9% saline solution as a control group whereas second (GR) and third (GB) groups received 0.5 mg ranibizumab and 1.25 mg bevacizumab by subconjunctival injection, respectively, on days first and 7 after lesion. The rabbits' corneas were extracted on the 14th day. Digital photographs of the corneas were obtained and the newly formed vessels were analyzed in a computerized system (google sketch-up program). The rates of these vessels were compared between the groups. Ranibizumab and bevacizumab were both effective on inhibition of angiogenesis, in comparison to 0.9% saline solution (P<0.05). Ranibizumab was found to be statistically more effective to reduce corneal neovascularization than bevacizumab (P<0.05). Bevacizumab and ranibizumab were found to be effective in inhibiting the corneal neovascularization in the rabbit cornea. Ranibizumab seemed more effective than bevacizumab on inhibiting corneal neovascularization in the rabbit cornea. Keywords: Ranibizumab, Bevacizumab, Rabbit cornea, Corneal neovascularization, Angiogenesis Korneal Neovaskularizasyonun Subkonjonktival Ranibizumab ve Bevacizumab Enjeksiyonu ile Tavşan Korneasında İnhibisyonu ÖzetBu çalışmanın amacı; subkonjunktival olarak uygulanan ranibizumab and bevacizumab'ın tavşan korneasında anjiyogenezis üzerine etkilerini değerlendirmekti. Yirmi dört adet Yeni Zelanda tavşanının korneaları neovaskülarizasyon oluşturmak için gümüş nitrat ile koterize edildi. Gözler 10 ml %0.9 salin solusyonu ile yıkandı. Tüm gözlerde eşit miktarda kimyasal yanık oluşturulmasına dikkat edildi. Koterizasyon sonrası 24. saatte tavşanlar üç gruba ayrıldı: Kontrol grubuna (GC) (n=8) subkonjunktival 0.02 ml %0.9'luk salin solüsyonu; Grub Ranibizumab'a (GR) (n=8) subkonjunktival olarak 0.5 mg ranibizumab ve Grup Bevasizumab'a (GB) (n=8) ise subkonjunktival olarak 1.25 mg bevacizumab 1. ve 7. günlerde uygulandı Topical antibiotik tedavisi sonrası, tavşan korneaları 14. günde çıkarıldı. Korneaların digital fotoğrafları alınarak yeni oluşmuş damarlar bilgisayar programı (google sketch-up programı) yardımıyla analiz edildi. Yeni oluşan damar yapılarının alanının kornea alanına oranları gruplar arasında değerlendirildi. Ranibizumab ve Bevasizumab'ın her ikisi de anjiyogenez inhibisyonunda %0.9 salin solüsyonuna kıyasla (P<0.05) daha etkili olduğu saptandı.Ranibizumab'ın korneal neovaskülarizasyon azaltıcı etkisi Bevasizumab'tan istatistiksel olarak anlamlı (P<0.05) derecede fazla bulundu. Bevasizumab ve Ranibizumab'ın tavşan korneasında neovaskularizasyonu inhibe etmekte etkili olduğu tesp...

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PET/CT Imaging of I-124–Radiolabeled Bevacizumab and Ranibizumab after Intravitreal Injection in a Rabbit Model

Cited by 53 publications

References 18 publications

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

MicroPET-CT evaluation of interstitial brachytherapy in pancreatic carcinoma xenografts

Inhibition of Corneal Neovascularization by Subconjunctival Injection of Ranibizumab and Bevacizumab in Rabbit Cornea

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