I've almost always gotten the best deals booking pretty far in advance. You can sometimes get better deals booking from outside the U.S., but I've never had much luck on that front--I booked some tickets to Lahore on Pakistan International a few years ago from Thailand, and found the prices quite similar to what they would have been from the States.

Islamabad, surprisingly, isn't that well-served an airport compared to Karachi, or, to a lesser extent, Lahore. So you'll probably want to fly out of KHI rather than Islamabad (which is a weird place anyhow, least enjoyable of the Pakistani cities I visited). But the Pakistani bus system is excellent, so it's easy and cheap enough to get between cities.

Either way (it's such an interesting itinerary I just checked prices on Kayak), it's not going to be super-cheap -- it's a very long flight, and I presume not a very common one. A one-way between Karachi and Istanbul starts around $600 on Turkish Airlines, and presumably goes up closer to your travel date. Another alternative might be to look into getting a cheap ticket from ISB to Dubai, then from Dubai to IST.... these are both popular, busy routes, so there might be multiple options. Plus you can shop at the world's most heavily air-conditioned luxury mall while you wait to change planes.

Good luck!