Whatever luster SPECT imaging has lost to rival technology PET in recent years could well be restored—and then some—as innovative applications built on newly developed radiopharmaceuticals make their way into common use.

“There won’t be any single application that supports and invigorates the SPECT market—it will be more like a combination of trends, from use of SPECT as an aid in early diagnosis of systemic illness and infection to use as a nuclear interventional tool,” says nuclear medicine physician Robert Bridwell, MD, MBA, chief medical officer of Integrated Medical Solutions in Charles Town, WVa.

The starting point for this gaining back of ground (though some no doubt would argue that SPECT has never yielded any) is the growing diversity of radiolabeled monoclonal antibodies for both diagnostic and therapeutic purposes.

“In the field of oncology, SPECT imaging allows us to now inject a tumor patient, systemically, with a radioactive marker delivered right to the surface of the tumor,” says Bridwell. “From there, we can deliver a very high dose of radiation to the tumor while minimizing the dose to the surrounding normal tissues. This is, of course, in contrast to conventional external beam radiation therapy where you have to shoot through the body.”

Most prominent among these new SPECT radiopharmaceuticals (prominent in part because they have been around the longest) are ibritumomab tiuxetan and tositumomab.

Ibritumomab tiuxetan was approved by the FDA in 2002 for treatment of patients with relapsed or refractory low-grade, follicular or transformed B-cell, non-Hodgkin’s lymphoma, a radiation-sensitive malignancy. Therapy involves an infusion of rituximab followed by an injection of an ibritumomab tiuxetan monoclonal antibody linked to the targeting radioisotope indium 111 and—7 to 9 days later—another infusion of rituximab, capped by a second injection of ibritumomab tiuxetan, only this time linked to the yttrium 90 radioisotope (which delivers the therapeutic benefit). Ibritumomab tiuxetan targets the CD20 antigen on the surface of mature B cells and B-cell tumors. Although yttrium 90’s high-energy beta rays have a path length of a mere five millimeters, some healthy neighboring cells invariably suffer collateral damage (the good news is that normal B cells usually replenish naturally in about 180 to 270 days).1

Similar to ibritumomab tiuxetan, tositumomab is a monoclonal antibody, only this time packaged with iodine 131. It is indicated for CD20-positive, follicular, non-Hodgkin’s lymphoma patients who have experienced a postchemotherapy relapse and are found to be refractory to rituximab. But there are important differences between tositumomab and ibritumomab tiuxetan. For one, the path length of tositumomab’s radiation is shorter and the clearance of its isotope faster than that of ibritumomab tiuxetan’s. Those are the pluses. On the negative side of the ledger, tositumomab’s isotope—in addition to emitting useful beta radiation—gives off gamma rays, which means the patient may have to be placed in hospital isolation as a precaution during therapy.2

VIEW TO A THRILL

Ibritumomab tiuxetan and tositumomab are not the only innovative radiopharmaceuticals for SPECT. Currently in Phase III clinical trials (and perhaps less than 18 months from reaching the market) are a number of new apoptosis agents. These will permit observation of programmed cell death, reports Robert E. Henkin, MD, FACNP, FACR, professor and vice chairman of the Department of Radiology and director of nuclear medicine at Loyola University Health System in Maywood, Ill.

“These agents will have wide application in both oncology and cardiology,” Henkin predicts. “With them, we’ll be able to look at the impact of chemotherapy interventions and ascertain which one of those produces the greatest cell death in a given setting. Or, for cardiology, we’re going to be able to look at how many grams of myocardium are potentially involved.”

Meanwhile, other researchers are broadening their evaluations of the dopamine uptake ligand beta-CIT, a SPECT agent that currently ranks among the most sensitive of biomarkers for the diagnosis of Parkinson’s disease. Beta-CIT targets the dopamine transporter on the dopamine neuronal terminals and quantifies the loss of those terminals. However, as things now stand, SPECT cannot completely discriminate between Parkinson’s disease and other Parkinson’s-like syndromes, a deficiency researchers hope to eventually rectify.

“At the moment, investigators are focused on trying to determine the best radiochemistry for beta-CIT,” says Bridwell. “SPECT’s three-dimensional localization of activity in the smaller structures within and near the brain makes this a more useful diagnostic tool than traditional planar imaging for patients with movement disorders. In addition to diagnosing Parkinson’s disease, it also helps assess the therapeutic response of the medications patients are placed on.”

Other relatively new SPECT radiopharmaceuticals of interest include:

  • Neutrophil-specific anti-CD15 monoclonal antibody. White blood cells, specifically polymorphonuclear neutrophils, are detected by a gamma camera in swift and stunning clarity when this technetium Tc 99m radiolabeled monoclonal antibody binds to them. The FDA has thus far approved it only for imaging and diagnosing equivocal appendicitis in patients 5 years and older (in Phase 3 clinical trials, 90% of positive appendicitis cases were diagnosed within just 1 hour). However, it is now being tested for other possible uses, including detection of osteomyelitis, pulmonary infection, fever of unknown origin, inflammatory bowel disease, and postsurgical infection.3
  • Technetium (99mTc) radiolabeled depreotide peptide. This radiopharmaceutical is being used to define lung lesions measuring more than 1 cm. 99mTc peptides work by attaching to a malignant tumor’s somatostatin receptors.4 Shih et al report that a 99mTc depreotide chest SPECT can uncover secondary lung cancer as well, such as pulmonary metastases from renal cell carcinoma.5 Elsewhere, another type of 99mTc peptide has garnered praise for its ability to help detect deep venous thrombosis.4

Some radiologists and nuclear medicine physicians have expressed concern that these and even newer SPECT radiopharmaceuticals might prove difficult to obtain—and for many of the same reasons that made FDG scarce in the earlier days of PET. Bridwell does not share that apprehensiveness.

“One of the advantages the SPECT market enjoys over the PET market is that its radiopharmaceuticals are more easily made and transported,” he says. “You don’t necessarily need a cyclotron and a big distribution network in support of it. Besides, the SPECT market is more mature than PET, so there are already widespread distribution networks throughout the world. Procurement is relatively easy, and I expect it will remain that way.”

BETTER TOGETHER

Even were SPECT radiopharmaceuticals to be in short supply, that still would not hinder SPECT operations at most enterprises where the modality is in service, users insist.

“SPECT really isn’t a pharmaceutical-based imaging system to begin with,” says Henkin. “It’s more like the CT of nuclear medicine. It produces CT-type images, cross-sectional images—but, in virtually every application, a more diagnostic image than you had with standard planar imaging.”

Admittedly, SPECT does suffer a serious shortcoming, and it is the inability to provide anatomic localization. That, however, has been quite satisfactorily addressed by pairing SPECT with a CT scanner.

“With SPECT, we see things very well, but we don’t always know where those things are,” says Henkin. “SPECT-CT, on the other hand, produces images that allow us to precisely localize what we’re looking at.”

Better yet, the SPECT-CT combination affords attenuation-correction quality to a degree previously unattainable, he adds.

“Attenuation correction is important because it significantly improves the quality of the images, which in turn means you can have much greater confidence in the interpretation,” says Henkin. “Also, because of this, we’re at long last able to go to quantification.”

Perhaps the biggest challenge to SPECT-CT penetration of the market comes from payors. Medicare, for instance, offers no hint that it will any time soon recognize the addition of CT to SPECT imaging as valid, Henkin points out.

But SPECT by itself is another matter. While it is readily reimbursed, the payments are not as generous as perhaps they ought to be.

“There’s actually nothing in the SPECT world today that is not reimbursable,” Henkin says. “The problems SPECT operators are encountering with insurance companies arise in part from how the CPT coding system is structured. Under that system, SPECT is often classified as an add-on procedure, which yields less than full reimbursement.”

Henkin speculates that CPT coding eventually will be revamped in ways favorable to SPECT as the modality becomes more and more widely accepted as a primary procedure. For now, however, the reimbursement realities of SPECT could dissuade more than a few imaging providers from establishing themselves in that field, he worries.

“If recovering the cost of the investment is problematic due to inadequate reimbursement, SPECT will not be able to spread,” says Henkin. “Money today is tighter than it’s ever been, and hospitals are less willing than ever to take a risk on things unless they can be assured they’ll get their money back on the investment rather quickly.”

Nevertheless, those enterprises gutsy enough to take a gamble on SPECT in spite of the current economics will be the ones to help push payors toward recognizing its true worth. The same applies to SPECT-CT.

“Once you’re in the game,” Henkin says, “referring physicians will be asking for these studies. As those studies are done, you’re going to start receiving kudos from the referrers. Your oncologist, for example, will come back and congratulate you for the correctness of your call—he’ll say, ‘You predicted that this chemotherapy would fail in this individual patient, and you were right.’ Or ‘You were absolutely right about the size of the ischemic zone for this other patient.’ And once you start providing the referring physicians with the missing pieces of the puzzle—which is what they’re clamoring for—it won’t be long afterward that payors start falling right in line behind them.”

In any event, SPECT should continue to be a more economical platform than PET when it comes to oncologic work, and that too, says Henkin, will encourage greater proliferation of SPECT imaging nationwide.

BATTLE LINES DRAWN

Still, do not expect SPECT and SPECT-CT to overtake PET. Nor, for that matter, for PET to supersede SPECT.

“There’ll always be a place for each, although PET likely will eat away at SPECT’s market share in the cardiovascular arena where we’re already seeing a lot of thinking about and actual movement toward the PET platform,” says Bridwell.

These days, about 30% of SPECT providers are cardiologists (although 60% of SPECT imaging is cardiovascular-focused), Henkin notes. Soon, though, oncologists and even neurologists could emerge as significant players too, ultimately taking SPECT market share from radiologists and nuclear medicine physicians.

“Economics is the driver here, more so than clinical concerns,” says Bridwell. “SPECT imaging, despite not being fully reimbursed, is well-enough reimbursed that it presents an attractive additional source of revenues for nonradiologists and non-nuclear medicine physicians. For example, neurologists treating Parkinson’s disease patients are establishing specialized clinics for memory and movement. As these evolve, they’ll reach a point where they can support their own gamma camera systems.”

Naturally, this is adding fuel to the burning political question of who should and should not be allowed to perform diagnostic imaging and radiotherapeutics.

“The battle lines are being drawn,” says Bridwell.

Henkin expects the frictions between radiology/nuclear medicine and their rivals in other fields over SPECT to lead to one of two outcomes: comity or combat. His money is on the former.

“The cost of these devices is significant enough that an institution can’t or won’t buy one for cardiology and then a separate one for radiology,” Henkin postulates. “They’ll have to share. And, because of that, they’ll have to learn to get along with one another. If they don’t, it’s going to be a bad situation for everybody.”

Whether radiologists and nuclear medicine physicians can cooperate with cardiologists and practitioners of other disciplines will not be known for some time. But, closer to home, it is almost a sure bet that SPECT—and, in particular, SPECT-CT—will bring radiology and nuclear medicine together in ways heretofore seldom known.

“A lot of radiologists have historically viewed nuclear medicine as second-class imaging,” says Henkin. “Conversely, a lot of nuclear medicine physicians have ignored cross-sectional imaging, understanding little if anything about CTA, for example. I think these two groups will quickly discover they have significant overlapping interests now, and will need to understand one another’s technology and approaches to practice if they have any hope of being truly successful in the future. If, for example, you plan to open a SPECT-CT unit or a high-end SPECT service, you’ll need to understand how the quantitative system works as well as how the imaging system works.”

This, says Bridwell, could inspire a lot more physiologic imaging in radiology departments.

“It could reach a point where radiologists and nuclear medicine physicians are scarcely distinguishable from one another in terms of tasks, because they’ll be doing more and more of the same thing,” he says. “So, if you’re a nuclear medicine physician, you’ll want to become cross-trained in anatomy, like your radiologist colleagues, in order to be equipped for success with SPECT-CT. If you’re a radiologist, you’ll want to become cross-trained in nuclear medicine techniques and physiology so you can fluently read SPECT-CT images.

“The way to look at it is this: hybrid scanners will drive the need for hybrid education. Simple as that.”

Rich Smith is a contributing writer for Decisions in Axis Imaging News.

References:

  1. Fact sheet. Available at: www.zevalin.com/factsheet.html. Accessed May 19, 2005.
  2. Fact sheet. Available at: www.lymphomation.org/compare-bexxar-zevalin.htm. Accessed May 19, 2005.
  3. Fact sheet. Available at: www.palatin.com/products/neutrospec/overview.asp. Accessed May 19, 2005.
  4. A peptide approach to the diagnosis of lung cancer in the presence of a solitary pulmonary nodule. Nuclear Medicine Update, 2001. Available at: www.nucmednet.com/neotect.htm. Accessed May 19, 2005.
  5. Shih W, Romero RA, Timothy M, Milan PP. 99mTc-depreotide chest SPECT demonstrates pulmonary metastases from renal cell carcinoma. J Nucl Med Technol. 2004;32:19-21.