by Wayne Webster

Positron Emission Tomography (PET) has become an accepted component of clinical patient imaging over the past six years. In oncology, neurology and cardiology PET is known and understood. Most believe that PET's future in Radiology is well established.

Within this discussion I will attempt to demonstrate that PET is nearing the end of its life cycle and will be replaced for most if not all of its clinical uses within the next few years.

To understand PET's future we need to understand its past. In 1985 PET was a research device and it remained this way until 1999 because there was no reimbursement by Medicare or almost any other payer worldwide.

Unfortunately for the companies involved with the development and production of PET imaging devices--CTI, Scanditronix, and Philips--limited reimbursement dramatically restricted the number of PET scanners sold.

Why was PET struggling for acceptance by the payers? Nuclear medicine and radiology were growing. PET was a nuclear medicine technique. What was wrong?

In retrospect, the answer is apparent. The isotopes used in PET whether Fluorine-18 as 18FDG, nitrogen-13, carbon-11 or oxygen-15 have half-lives ranging from 2 hours to 2 minutes respectively. The isotopes that made PET attractive as a research and clinical imaging tool were at the core of the problem. Even though PET is a nuclear medicine application, because of the short half-lives of the isotopes it didn't fit the well established nuclear medicine business model.


THE NUCLEAR MEDICINE BUSINESS MODEL


In nuclear medicine a large centrally located radiopharmaceutical vendor develops and distributes product either to a local nuclear pharmacy or directly to the end-user. This is all possible because the half-lives of the isotopes used in standard nuclear medicine range from 6 to 73 hours.

The longer half-lives of single photon isotopes allow for the efficient production and distribution of radiopharmaceuticals over large distances. The radiopharmaceutical manufacturer supports the product with marketplace education (for end user business growth), FDA approval and most important a ready-to-inject dose.

For the nuclear medicine end-user this business model provides real benefits. Without the need to make or compound their own radiopharmaceuticals the nuclear medicine imaging clinic can focus on developing a practice, eliminate inventory risk and remove the need for high-level personnel for the preparation of doses.

PET's isotopes with half-lives of 2 hours to 2 minutes eliminated the large radiopharmaceutical supplier from the business model. Without the large manufacturer's involvement the tasks of educating the referring physician, and seeking FDA regulatory approval, were now spread over hundreds of small, independent and sometimes competing imaging centers and nuclear pharmacies.

The short half-lives of the PET isotopes eliminated the large manufacturer from the nuclear medicine business model. This made it very difficult for PET to succeed. The equipment vendors added more fuel to the fire when they implemented a strategy in the late 1980s that sealed PET's fate.


THE EQUIPMENT VENDORS' PLAN


In the late 1980s and into the 1990s there was great frustration on the part of the PET scanner manufacturers because there was no reimbursement. Siemens had purchased a major share of CTI. GE Healthcare joined in with the purchase of Scanditronix. The marketplace thought this would bring PET into the clinical arena, encouraging sales of equipment and Medicare reimbursement. To everyone's surprise nothing happened.

The equipment vendors examined the radiopharmaceutical manufacturers' approach to product introduction and believed that, to get PET procedures reimbursed by Medicare, the marketplace needed FDA approval of PET radiopharmaceuticals.

18FDG was the obvious candidate for the FDA approval process. It was the most widely used PET imaging agent by those who either made their own or bought it from the local nuclear pharmacy's operating cyclotrons.

18FDG was chosen because the fluorine -18 tag (with a 2-hour half-life) on deoxyglucose made it possible for the nuclear pharmacy to transport the radiopharmaceutical 30 minutes away by automobile.

If the equipment vendors were correct then, with 18FDG approval by FDA, reimbursement from Medicare would soon follow. They believed that with reimbursement the PET scanner market would expand, dramatically increasing unit sales. Unfortunately, after several years, millions of dollars and an FDA approval for 18FDG there still was no reimbursement. Medicare reimbursement didn't begin to happen until late 1999.

Taking the path of FDA approval for 18FDG set a precedent for the future approval of all PET radiopharmaceuticals. From this point forward new PET radiopharmaceuticals would have to go through the FDA process. But, who would take on such a large and costly assignment? Would the local nuclear pharmacy, a hospital or an imaging clinic shoulder this expense? The answer is no one would. No small producer could justify the expense.

Eventually in 1999 limited Medicare reimbursement for PET applications using 18FDG began. Over the next four years a number of indications were added. These expanded the usefulness of PET for diagnosing and staging various cancers. Unfortunately in choosing the FDA approval path the PET equipment vendors had unwittingly prevented any future expansion beyond those applications using 18FDG.

The sales of PET scanners in 2000, and two years later hybrid PET/CTs, accelerated on the news of Medicare reimbursement. Everyone believed that PET had arrived. The vendors compared the future sale of PET scanners to that of MRI.

But the equipment vendors were not considering these limitations of PET imaging:
-Short half-lives eliminated large-scale production and distribution of radiopharmaceuticals by centralized vendors.
-The short half-life of PET isotopes limited the delivery area for a nuclear pharmacy. A one-half hour driving radius in any major metro area can be less than 10 miles.
-The process that resulted in the approval of 18FDG by the FDA now demanded that all other PET radiopharmaceuticals be subjected to the same rigorous, high-cost regulatory process.


There was something else that would change the future potential for clinical PET imaging. As a research tool PET was lauded for its ability to take quantitative physiological measurements. The image that the PET scanner produced was interesting but not as important as the measurement of the uptake of the various PET radiopharmaceuticals like 18FDG.

As PET transitioned from being a research instrument to a clinical tool, its ability to take quantitative measurements became less important. It took too much time to take such measurements in an environment driven by throughput. As PET became more valued for the images it took than for the measurements it could make, its usefulness was diminished.

Another reason for the change in focus for PET from that of a quantitative measurement device to a qualitative imaging device may be due to the other PET isotopes and their radiopharmaceutical derivatives not being available. Therefore the only avenue that could be used for PET was as a qualitative clinical imaging device. No matter the reason, PET has been limited by many factors. These all lead to the replacement of PET with another modality.

If you still doubt that PET will be replaced with something else, let's examine how the equipment vendors have managed PET's life cycle.

In 1999, GE, Siemens and Philips were producing dedicated PET scanners. The first reimbursement was implemented and sales of dedicated PET scanners for clinical applications began to grow. By 2000 reimbursement is expanded and PET scanner sales increase. In mid-year 2001 Siemens introduces the hybrid PET/CT. GE soon follows, with Philips a year later.

Those with dedicated PET scanners that are a year or two old are encouraged by the equipment vendors to replace them and trade up to PET/CT. By 2004 GE and Siemens stop producing and selling dedicated PET in favor of hybrid PET/CT scanners. Then they increase the capability of the hybrid PET/CT scanner by replacing the single-slice CT with 4-, 8-, 16-, 32- or 64-slice CT scanners. By 2006 sales have flattened for all of the companies.

PET's life-cycle was in its infancy in 2000 and six years later it's mature. Usually a medical device life-cycle will last seven years or more. In six years the manufacturers moved quickly through three life cycles.
- Life Cycle #1 The PET Only Scanner
- Life Cycle #2 The Hybrid PET/Single slice CT
- Life Cycle #3 The Hybrid PET/Multi-slice CT
Manufacturers usually wish to stretch the life cycle. The longer the life cycle the better the return on investment. When there is a replacement for the current technology in the wings, then manufacturers will do all they can to place as many units in the field as possible.


IF PET'S FATE IS SEALED, WHAT'S NEXT?

The answer is SPECT/CT.

Let's briefly consider the issues driving this process:
- PET is limited by the availability of radiopharmaceuticals.
- PET is used primarily as a qualitative imaging device.
- SPECT is a nuclear imaging device that is installed everywhere.
- SPECT fits the Nuclear Medicine business model.
- SPECT uses radiopharmaceuticals with longer half-lives.

Large manufacturers of radiopharmaceuticals can participate and support the market with product, distribution, education and regulatory.

SPECT is a qualitative imaging technique that can make use of existing and newly developed SPECT radiopharmaceuticals to produce similar clinical results to qualitative PET.

SPECT/CT was introduced several years ago and it continues to be developed and improved. Each year more sophisticated CTs are added.

GE, Siemens and Philips all have a SPECT/CT scanner on the market.

Radiopharmaceutical companies are investigating and developing single photon consumables. These are intended to replace and provide similar capability to PET/CT.

Within the next 60 months, PET and PET/CT will be replaced in almost all clinical applications by SPECT/CT. With all of the limitations placed upon PET by nature and marketplace decisions can there be any other answer?


About the Author

Wayne Webster founded ProActics Consulting in 2003 for the purpose of supporting the business planning efforts of companies, clinics, hospitals, new opportunities in medical devices, high-tech electronics and businesses requiring
strategic business planning guidance.

Wayne has provided business planning services to GE Healthcare, Perkin Elmer Inc., Neusoft Group, Ltd. (China), and The I.R.I.S. In addition he has supported the business planning process for dozens of imaging clinics and hospitals seeking support as they considered the acquisition of medical imaging technology for current and emerging clinical applications. Wayne also serves as the Managing Director for Diagnostix Plus, Inc. In this capacity he supports the development and implementation of new business opportunities for Diagnostix Plus.