Vascular radiolesion as a deleterious effect of high-dose-rate intraarterial brachytherapy with samarium-153 in hypercholesterolemic rabbits.

OBJECTIVE: This study was designed to evaluate vascular morphological and morphometric changes induced by brachytherapy with samarium-153 (Sm-153) at high doses in hypercholesterolemic rabbits. METHODS: Forty-three New Zealand White hypercholesterolemic rabbits were analyzed, and the total of 86 iliac arteries underwent balloon angioplasty injury. The rabbits were divided into three different groups: two irradiation groups (IG) assigned to 15 Gy (n=14) and 60 Gy (n=36) irradiation doses, respectively, and a control group (n = 36). Histomorphometric and qualitative histological analyses were performed for tissue evaluation. RESULTS: Significant reductions were found in neointimal proliferation (NIP) (p< 0.0001), media area (MA) (p<0.0001) and percent stenosis (p<0.0001) in the 15-Gy IG, compared to the other groups. The 60-Gy IG had the higher rate of NIP, increase in media and vessel areas (VA) and percent stenosis. The 60-Gy IG also showed the greatest number of xanthomatous cells (60-Gy IG: 86.11% and 15-Gy IG: 14.29%, p<0.0001) and the highest amount of hyaline amorphous tissue (60-Gy IG:58.33% and 15-Gy IG:0%, p=0.0001) and vascular proliferation (60-Gy IG:30.56% and 15-Gy IG:0%, p=0.0221). No statistically significant differences were found among groups concerning other tissue analyses. CONCLUSION: The high-dose irradiation of 60 Gy resulted in intense cell proliferation considered vascular radiolesion, unlike the 15-Gy dose, which was associated with an excellent inhibition of neointimal proliferation.

Radiolesão vascular como efeito deletério da braquiterapia intra-arterial com dose elevada de Samário-153 em coelhos hipercolesterolêmicos / Vascular radiolesion as a deleterious effect of high-dose-rate intraarterial brachytherapy with Samarium-153 in hypercholesterolemic rabbits / Vascular radiolesion as a deleterious effect of high-dose-rate intraarterial brachytherapy with Samarium-153 in hypercholesterolemic rabbits

OBJETIVO: Este estudo tem por objetivo avaliar as alterações vasculares morfológicas e morfométricas induzidas pela braquiterapia com Samário-153 (153 Sm) em coelhos hipercolesterolêmicos, com doses elevadas. MÉTODOS: Foram analisados 43 coelhos hipercolesterolêmicos, brancos, da raça New Zealand, e o total de 86 artérias ilíacas submetidas a lesão por balão de angioplastia. Divididos em três grupos: dois (GI) irradiados com as doses de 15Gy (n=14) e 60Gy (n=36) e um grupo controle (n=36). Foram realizadas avaliação histológica morfométrica e análise histológica qualitativa para análise tecidual. RESULTADOS: Foram observadas uma redução significativa da neoproliferação intimal (NPI) no GI 15 Gy (p<0,0001), uma redução da área de camada média (ACM) (p<0,0001) e por cento estenose (p<0,0001) comparada com os demais grupos. O GI 60 Gy teve o maior índice de PNI, aumento da ACM, AV e porcentagem de estenose. No GI 60 Gy, observou-se maior número de células xantomatosas (GI 60Gy:86,11 por cento e GI 15Gy:14,29 por cento, p<0,0001), tecido amorfo hialino (GI 60Gy:58,33 por cento e GI 15 Gy:0 por cento, p=0,0001) e proliferação vascular (GI60 Gy:30,56 por cento e GI15 Gy:0 por cento, p=0,0221). Outras análises teciduais não apresentaram diferença estatística entre os grupos. CONCLUSÃO: A dose elevada de 60Gy ocasionou intensa proliferação celular considerada radiolesão vascular, ao contrário da dose de 15Gy que apresentou excelente inibição da neo-proliferação intimal.

OBJECTIVE: This study was designed to evaluate vascular morphological and morphometric changes induced by brachytherapy with samarium-153 (Sm-153) at high doses in hypercholesterolemic rabbits. METHODS: Forty-three New Zealand White hypercholesterolemic rabbits were analyzed, and the total of 86 iliac arteries underwent balloon angioplasty injury. The rabbits were divided into three different groups: two irradiation groups (IG) assigned to 15 Gy (n=14) and 60 Gy (n=36) irradiation doses, respectively, and a control group (n = 36). Histomorphometric and qualitative histological analyses were performed for tissue evaluation. RESULTS: Significant reductions were found in neointimal proliferation (NIP) (p< 0.0001), media area (MA) (p<0.0001) and percent stenosis (p<0.0001) in the 15-Gy IG, compared to the other groups. The 60-Gy IG had the higher rate of NIP, increase in media and vessel areas (VA) and percent stenosis. The 60-Gy IG also showed the greatest number of xanthomatous cells (60-Gy IG: 86.11 percent and 15-Gy IG: 14.29 percent, p<0.0001) and the highest amount of hyaline amorphous tissue (60-Gy IG:58.33 percent and 15-Gy IG:0 percent, p=0.0001) and vascular proliferation (60-Gy IG:30.56 percent and 15-Gy IG:0 percent, p=0.0221). No statistically significant differences were found among groups concerning other tissue analyses. CONCLUSION: The high-dose irradiation of 60 Gy resulted in intense cell proliferation considered vascular radiolesion, unlike the 15-Gy dose, which was associated with an excellent inhibition of neointimal proliferation.

Samarium-153 for intravascular irradiation therapy with liquid-filled balloons to prevent restenosis: acute and long-term results in a hypercholesterolemic rabbit restenosis model.

BACKGROUND: It has been shown that irradiation with either beta and gamma sources inhibit neointimal formation. Samarium-153 ((153)Sm) is an isotope with 0.8 MeV, subdivided in three different beta energies and 103 keV of gamma energy. This compound has been tested and used in humans for palliation of pain from bone metastases. The aim of the present study was to evaluate the feasibility and efficacy of brachytherapy with (153)Sm-filled balloon to inhibit neointimal formation in rabbits after balloon overstretch injury. METHODS: Nineteen rabbits underwent balloon injury in their iliac arteries. In 12 animals (control), oversized balloons filled with saline solution were inflated up to 5 atm for a period of 5 min. In 7 rabbits, the same procedure was performed but using balloons filled with (153)Sm. In all cases, both iliac arteries were treated. The prescribed radiation dose was 15 Gy at 1 mm depth. After 30 days, the animals were sacrificed and their arterial segments were analyzed. Radiation exposure at the animal chest to the table and at a distance of 1 m from the table was measured. RESULTS: Histopathologic analysis showed a striking reduction in the amount of neointima in the irradiated arteries compared with control vessels (0.36+/-0.21 vs. 1.07+/-0.56 mm(2), P<.01). The dose delivered to the animal chest was 21.5 mR/h, whereas only 1.9 mR/h was measured at the table and virtually no radiation could be detected at a distance of 1 m from the table. CONCLUSIONS: Brachytherapy with (153)Sm was feasible with minimal personnel exposure radiation and effectively inhibited neointimal formation in this experimental model. These results warrant further experimental and clinical investigations.