Preheat oven to 350 degrees F and grease a 9x13 inch baking dish with cooking spray. Set aside.
Melt 1/2 cup butter over medium heat in a large stockpot.
Slowly sprinkle on flour then whisk for 60 seconds.
Slowly pour in milk, whisking constantly.
Stir in salt, pepper, garlic powder, onion powder, mustard powder, and sour cream.
Turn heat to low then stir in cheeses, little by little (I do a handful at a time), letting the cheese melt before adding more cheese. Keep adding cheese and stirring constantly until all the cheese has been added and melted.
Remove from heat and gently stir in cooked macaroni then transfer to prepared baking dish.
Panko Topping
In a small bowl, stir together 1/4 cup melted butter, panko, salt, and paprika.