Gerald W. Keister

Complementary methods have helped physicians at M. D. Anderson Cancer Center in Texas improve the success rate of surgical treatments for ectopic parathyroid adenoma. Presurgical SPECT/CT combined with an intraoperative assay for parathyroid hormone is credited with a 97% success rate for the surgical excision of the neoplasms and the near-elimination of failed parathyroidectomy and follow-up surgery.

Dual-phase Tc-99m sestamibi (MIBI) SPECT/CT localizes the adenomas, said Dr. Rodolfo Nunez, an assistant professor of nuclear medicine. Nunez and colleagues adopted an imaging strategy developed by Dr. Raymond Taillefer, a nuclear physician at the Centre Hospital of the University of Montreal in Quebec, Canada, that is based on the differential wash-out of sestamibi from normal thyroid and abnormal parathyroid tissue.

The rate of wash-out from abnormal parathyroid tissue, such as parathyroid adenoma, is much slower than that from normal thyroid tissue, Nunez said. In nearly all cases, sestamibi uptake can still be observed in diseased parathyroid tissue in delayed imaging obtained 90 minutes after tracer administration. The agent will have completely cleared from normal tissue by then.

Technetium-based sestamibi imaging is more than 90% sensitive for localizing parathyroid adenomas in patients with primary hyperparathyroidism, Nunez said. Sensitivity has risen even higher with the adoption SPECT/CT fusion imaging, which more reliably visualizes easy-to-miss ectopic sites in the retroesophageal space and mediastinum.

Ectopic parathyroid glands are a fluke of human embryonic development affecting about one in five U.S. residents. Instead of migrating to a normal position adjacent to the thyroid gland, ectopic parathyroid glands usually settle at the base of the tongue, but their resting place can be anywhere along the path of the initial descent of the thyroid.

Primary hyperparathyroidism (HPT) is characterized by excessive secretion of parathyroid hormone (PTH), leading to excess calcium or low phosphate concentrations in the blood. Parathyroid adenomas cause more than 80% of HPT cases.

A typical Tc-99m MIBI SPECT/CT exam to localize parathyroid adenoma involves early and delayed imaging of the neck and upper thorax and/or mediastinum after an intravenous injection of 20 to 25 mCi of Tc-99m sestamibi. Early imaging is performed about 15 to 20 minutes after the injection. The patient returns to the scanner for delayed imaging completed from 1.5 to two hours after injecting the tracer, depending on the nuclear medicine physician's preference. The SPECT/CT scan is performed between these two planar studies.

"SPECT/CT allows surgeons to plan their surgical approach to the adenoma meticulously," said Dr. Partha Ghosh, clinical marketing manager for molecular imaging at Siemens Medical Solutions. "It also assures that the patient spends less time in surgery because the surgeon knows exactly where to look."

Accurate localization of the relative positions of ectopic parathyroid adenomas and immediately adjacent anatomic structures is crucial to planning minimally invasive surgery, Nunez said.

"Surgeons are now making very small incisions, some as short as one inch in length, so they really appreciate the benefit of SPECT/CT to tell them precisely where the ecotopic adenomas are located," he said.

PTH concentration levels measured from blood samples drawn before surgery and five, 10, and 15 minutes after resection produce a quantifiable measure of surgical success. Surgery is deemed successful when the PTH value of the immunoassay performed 10 minutes after adenoma resection is at least 50% lower than baseline PTH level observed before surgery, Ghosh said.

Smaller changes in PTH level suggest the presence of a second ectopic gland, Ghosh said.

"But when you see a sharp drop in PTH after resection, you're sure the surgery is complete, and the patient will not have a recurrence," he said.

Articles

Complementary methods have helped physicians at M. D. Anderson Cancer Center in Texas improve the success rate of surgical treatments for ectopic parathyroid adenoma.

SPECT/CT plus assay boosts surgical success

Time is not on the side of molecular imaging researchers who hope to expand the use of the carbon-11 tracer into clinical PET practice.

Carbon-11 is popular with MI scientists, but its short 20-minute half-life has raised formidable barriers for its adoption outside of academic healthcare. Most community-based hospitals cannot afford an onsite cyclotron that is essential for its production and swift delivery to radiology departments for diagnostic use. Due to their small numbers, C-11 advocates have been discouraged from seeking federal regulatory clearance and reimbursement. Their inability to take action has contributed to disincentives for clinical use of C-11.

The migration of molecular probes from bench to bedside would be swifter and cheaper if C-11 were as easily accessible as fluorine-18, which can be produced and distributed from regional radiopharmacies because of its six-hour half-life.

Basic scientists often use C-11 because the high-energy positron-emitting isotope is easily bonded to most chemical compounds that show diagnostic or therapeutic promise. It does not alter the structure, reaction time, or mechanisms of action used by biological agents, and it labels molecules without changing their biological specificity, maximizing the probability of successful migration from the laboratory to animal and human testing.

C-11's 20-minute half-life can be advantageous, said Dr. Juri Gelovani, director of experimental diagnostic imaging at M.D. Anderson Cancer Center in Houston. It minimizes radiation exposure and enables repeat measurements without interference from previous studies.

Most F-18-based radiopharmaceuticals were first paired with C-11 in the laboratory. F-18 thymidine, for example, evolved from studies of C-11 thymidine that demonstrated its ability to measure cell proliferation.

Other investigational agents include C-11 PIB for Alzheimer's disease, C-11 methionine for tumor recurrence, C-11 choline for prostate cancer, and C-11 raclopride for neurological disorders. Designing chemical compounds bonding the base molecule of these agents with F-18 can be difficult, expensive, and time-consuming.

Experimental applications of C-11 probes have begun in humans at academic institutions equipped with cyclotrons and could potentially migrate quickly to community-based hospitals that acquire a baby cyclotron or linear accelerator designed to make C-11 generation more affordable. Systems from AccSys Technology, GE Healthcare, and Siemens Medical Solutions cost about $2 million.

But potential purchasers are biding their time because of regulatory and reimbursement problems, according to Ward Digby, director of biomarker product management at Siemens.

"It's a Catch-22, because since these carbon-based radioisotopes are not approved or reimbursable, they are not being used in local hospitals," he said. "Thus, community hospitals have no incentive to invest in a baby cyclotron. There is little interest, therefore, in conducting large, expensive clinical studies to get C-11 tracers approved."

MIO Briefing

Carbon-11 tracer's 20-minute half life makes it too expensive for most community hospitals, but it can minimize radiation exposure and enable repeat measurements without interference from previous studies.

Gerald W. Keister

Articles

SPECT/CT plus assay boosts surgical success

MIO Briefing

SPECT/CT plus assay boosts surgical success

Short half-life handicaps clinical adoption of carbon-11 radioisotope