Radioguided surgery of parathyroid adenomas and recurrent thyroid cancer using the "low sestamibi dose" protocol.

PURPOSE: The aim of this study was to establish the clinical efficacy of the "low sestamibi dose" (LSD) protocol to perform thyroid and parathyroid radioguided surgery in a large series of patients homogeneously studied and operated on by the same surgeon. The LSD protocol was initially developed in our center to cure primary hyperparathyroid (PHPT) patients with a high likelihood of a solitary parathyroid adenoma (PA) by minimally invasive radioguided surgery (MIRS). Since then, the same protocol has been applied to differentiated thyroid cancer (DTC) patients with 131I-negative, but sestamibi-positive, locoregional recurrent disease in order to obtain radical radioguided extirpation of tumoral lesions at reoperation. STUDY DESIGN: We reviewed the clinical charts of 453 consecutive patients referred at the surgical department at Padova University (Padova, Italy) to investigate a PHPT or a DTC recurrence: 336 patients (74.2%) met the inclusion criteria for radioguided surgery, and these patients were analyzed for the aim of this study. There were 298 patients affected by PHPT with a high likelihood of a solitary sestamibipositive PA and 38 DTC patients affected by 131I-negative, but sestamibi-positive, locoregional recurrence. All patients underwent a preoperative imaging work-up, including sestamibi scintigraphy (doubletracer subtraction scan in PHPT patients and single-tracer, wash-out scan in DTC patients) and high-resolution neck ultrasonography (US). The LSD protocol we developed consists of the intravenous injection of a very low (1 mCi) sestamibi dose in the operating theater just 10 minutes before commencing intervention for the purpose of radioguided surgery only. At variance with the traditional "high (20-25 mCi) sestamibi dose (HSD)" protocol in which imaging and radioguided surgery are obtained in the same day, in the LSD protocol, imaging and radioguided surgery are performed in different days. The LSD protocol allows some advantages over the HSD protocol: (1) more time for acquiring and interpreting preoperative imaging (planar scintigraphy, single-photon emission computed tomography [SPECT], US); (2) an accurate selection of patients to whom MIRS is offered, especially in countries where the prevalence of nodular goiter with sestamibi-avid thyroid nodules (exclusion criteria for MIRS) is relatively high, as in mid-south-European countries; (3) it facilitates the work planning in the operating theater (bilateral neck exploration requires an operating time of at least double to that of MIRS); and (4) the radiation exposure dose to operating theater personnel is very low-substantially negligible, using the LSD protocol: This aspect assumes great importance in countries where radioproteximetric rules are stringent, as in Europe. RESULTS: PHPT patients. MIRS was successfully performed by a 1.5-2-cm skin incision in 287 of 298 PHPT patients (96.3%) in whom such an approach was scheduled on the basis of preoperative imaging, including 41 of 57 patients (71.9%) who had previously received thyroid or unsuccessful parathyroid surgery in another center. No case of major intraoperative complication was recorded. No case of persistent or recurrent PHPT was observed during postsurgical follow-up. DTC patients. A total of 79 metastatic lesions were intraoperatively detected by the gamma probe and successfully removed (68 of them had been correctly visualized at preoperative sestamibi scintigraphy). During subsequent follow-up, 18 patients (72%) were considered disease-free, whereas 7 had persistent disease (increased serum thyroglobulin levels). The radiation exposure dose to the surgeon using the LSD protocol was 1.2 uSi/hour, that is, 20-30-fold lower than that delivered with the HSD protocol used for PHPT patients and with the 131I protocol used for DTC patients with recurrence. CONCLUSIONS: On the basis of our data, it can be concluded that the LSD protocol is a safe and effective protocol to perform in both MIRS in PHPT patients and radioguided reoperation in DTC patients with 131I-negative recurrence. Furthermore, from a radioproteximetric point of view, in comparison with other radioguided protocols used for the same purposes, the LSD protocol minimizes the radiation-exposure dose to the surgeon and operating theater personnel.

Role of gamma probes in performing minimally invasive parathyroidectomy in patients with primary hyperparathyroidism: optimization of preoperative and intraoperative procedures.

OBJECTIVE: In the last decade, surgery of primary hyperparathyroidism (HPT) due to a solitary adenoma has moved on from the traditional wide bilateral neck exploration (BNE) to more limited approaches such as unilateral neck exploration and minimally invasive parathyroidectomy. DESIGN: To define the role of intraoperative gamma probe and injection of a low (99m)Tc-MIBI dose in performing minimally invasive radio-guided surgery (MIRS) in HPT patients with a solitary parathyroid adenoma. METHODS: From September 1999 to July 2002, 214 patients with primary HPT entered the study. All patients were preoperatively investigated by a (99m)Tc-pertechnetate/MIBI subtraction scan and high-resolution neck ultrasound. The intraoperative technique we developed differs from other previously described techniques being based on the injection of a low (37 MBq) MIBI dose in the operating theatre a few minutes before the beginning of intervention. RESULTS: On the basis of scan/ultrasound findings 147 patients were selected for a MIRS and 144 of them (98%) were successfully treated by this approach: a solitary parathyroid adenoma was removed through a small 2-2.5 cm skin incision with a mean operative time of 35 min, and a mean hospital stay of 1.2 days. In the other 67 patients with scan/ultrasound evidence of concomitant nodular goiter (n=45) or multi-gland disease (n=13) or with a negative scan (n=9), the gamma probe was utilized during a traditional BNE. A low 37 MBq MIBI dose proved to be sufficient to perform a MIRS; moreover it delivered to the patient and surgeon a low, negligible, radiation exposure dose. CONCLUSIONS: The combination of a (99m)Tc-pertechnetate/MIBI subtraction scan and neck ultrasound appears to be an accurate imaging protocol in selecting primary HPT patients as candidates for a MIRS. A MIBI dose as low as 37 MBq injected in the operating theatre just before the start of surgery appears to be adequate to perform radio-guided surgery.

Determinant role of Tc-99m MIBI SPECT in the localization of a retrotracheal parathyroid adenoma successfully treated by radioguided surgery.

PURPOSE: The authors' aim was to evaluate the role of MIBI SPECT acquired just after planar pertechnetate-MIBI (TcO(4)-MIBI) subtraction scintigraphy in planning radioguided surgery in a patient with persistent primary hyperparathyroidism after initial surgery performed to treat a retrotracheal parathyroid adenoma (PA). METHODS: A 73-year-old man with persistent primary hyperparathyroidism after a previous left parathyroidectomy and left thyroid lobectomy is described. The patient was examined in our center in a single-day preoperative imaging protocol based on findings of planar TcO(4)-MIBI subtraction scintigraphy, MIBI SPECT, high-resolution neck ultrasound, and computed tomography. RESULTS: Neck ultrasound did not reveal enlarged parathyroid glands. Findings of a neck-chest computed tomographic scan were also inconclusive. Instead, planar scintigraphy clearly depicted a single focus of MIBI uptake over the thyroid gland in a median position. The SPECT examination precisely localized a PA in the retrotracheal space. The day after imaging, the patient underwent unilateral left cervical surgical exploration. A 16 x 21 mm PA was easily detected using the gamma probe technique after injection of a low dose of 37 MBq (1 mCi) Tc-99m MIBI, and the PA was rapidly removed with limited surgical trauma. Rapid serum PTH and calcium levels normalized after intervention and remained in the normal range during subsequent follow-up. CONCLUSIONS: The current data indicate the importance of preoperative imaging with MIBI scintigraphy in patients with primary hyperparathyroidism and strongly support the utility of MIBI SPECT acquisition in PAs located deep in the neck and in ectopic sites. Furthermore, the gamma probe can help the surgeon to detect the PA during surgery and to minimize the surgical trauma in patients who have had previous thyroid or parathyroid surgery.

Functional scintigraphy of the adrenal gland.

Over the last 30 years nuclear medicine imaging of the adrenal gland and its lesions has been achieved by the exploitation of a number of physiological characteristics of this organ. By seeking and utilising features which are quantitatively or qualitatively different from those of the adjacent tissues, functional depiction of the adrenal gland and its diseases, which in most cases retain the basic physiology of their tissue of origin, including both the cortex and the medulla, are now a useful clinical reality. Agents widely used in clinical practice include: (a) uptake and storage of radiolabelled cholesterol analogues via the low density lipoprotein (LDL) receptor and cholesterol ester storage pool in the adrenal cortex ((131)I-6-beta-iodomethyl-norcholesterol, (75)Se-selenomethyl-norcholesterol); (b) catecholamine type I, presynaptic, uptake mechanism and intracellular granule uptake and storage mechanism in the adrenal medulla and extra-adrenal paraganglia ((131)I-, (123)I- and (124)I-meta-iodo-benzyl-guanidine (MIBG), (18)F-metafluoro-benzyl-guanidine); (c) cell surface receptor binding of peptides/neurotransmitters/modulators such as for the family of five subtypes of somatostatin receptors ((123)I-tyr-octreotide, (111)In-DTPA-octreotide, (111)In-DOTA-octreotide and many others); (d) although not specific for the adrenal gland, increased glycolysis by tumours, particularly the most malignant varieties, (18)F-2-fluoro-d-deoxyglucose can thus be expected to depict certain malignant lesions such as malignant pheochromocytomas (particularly the minority which are not detected by MIBG) and adrenal incidentalomas (particularly when they occur in patients with known extra-adrenal malignancies). There are a variety of adrenal tissue characteristics with potential for exploitation but which are not currently in clinical use, and which may, nevertheless, have potential as imaging agents. These include: (a) inhibitors of adrenal cortical steroid hormone synthesis enzymes (e.g. radiolabelled analogues of metyrapone); (b) radiolabelled lipoproteins which bind to adrenocortical LDL receptors; (c) inhibitors of catecholamine biosynthesis enzymes (e.g. radiolabelled analogues of tyrosine and related amino acids); (d) cell surface receptors for various peptides and hormones which may be over-expressed on adrenal cortical or adrenal medullary tumours (e.g. radiolabelled analogues of ACTH on adrenocortical cells of zona fasciculata or zona glomerulosa origin, neurotransmitter/hormone message peptides binding to cell surface receptors such as bombesin, vasoactive intestinal polypeptide, cholecystokinin and opiate peptides); (e) the adrenal cortex can also synthesise cholesterol ab initio from acetate, and preliminary studies with (11)C-acetate positron emission tomography have shown interesting results.

Pilot study of iodine-131-metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma.

PURPOSE: The survival for children with relapsed or metastatic neuroblastoma remains poor. More effective regimens with acceptable toxicity are required to improve prognosis. Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) selectively targets radiation to catecholamine-producing cells, including neuroblastoma cells. A pilot study was performed to examine the feasibility of a novel regimen combining (131)I-MIBG and myeloablative chemotherapy with autologous stem-cell rescue. PATIENTS AND METHODS: Twelve patients with neuroblastoma were treated after relapse (five patients) or after induction therapy (seven patients). Eight patients had metastatic and four had localized disease at the time of therapy. All patients received (131)I-MIBG 12 mCi/kg on day -21, followed by carboplatin (1,500 mg/m(2)), etoposide (800 mg/m(2)), and melphalan (210 mg/m(2)) administered from day -7 to day -4. Autologous peripheral-blood stem cells or bone marrow were infused on day 0. Engraftment, toxicity, and response rates were evaluated. RESULTS: The (131)I-MIBG infusion and myeloablative chemotherapy were both well tolerated. Grade 2 to 3 oral mucositis was the predominant nonhematopoietic toxicity, occurring in all patients. The median times to neutrophil (> or = 0.5 x 10(3)/microL) and platelet (> or = 20 x 10(3)/microL) engraftment were 10 and 28 days, respectively. For the eight patients treated with metastatic disease, three achieved complete response and two had partial responses by day 100 after transplantation. CONCLUSION: Treatment with (131)I-MIBG in combination with myeloablative chemotherapy and hematopoietic stem-cell rescue is feasible with acceptable toxicity. Future study is warranted to examine the efficacy of this novel therapy.

An ectopic mediastinal parathyroid adenoma accurately located by a single-day imaging protocol of Tc-99m pertechnetate-MIBI subtraction scintigraphy and MIBI-SPECT-computed tomographic image fusion.

PURPOSE: Because ectopic parathyroid adenoma (PA) is a frequent cause of failed initial surgery, an imaging approach with accurate preoperative localization is recommended by some authors in patients with primary hyperparathyroidism (HPT). METHODS: The authors describe a 52-year-old woman in whom primary HPT was diagnosed incidentally during a screening program for osteoporosis. The peculiarity of this case is that the patient was examined before operation in a single-day multimodal imaging protocol based on the combination of high-resolution cervical ultrasound, planar Tc-99m pertechnetate-MIBI scans, and an MIBI-SPECT-computed tomographic (CT) image fusion study. An ectopic PA was accurately located in the upper middle mediastinum, close to the lower margin of the sternal notch. RESULTS: Guided by the MIBI-SPECT-CT fusion images, the surgeon performed a limited median sternotomy and easily removed the PA that was revealed before operation. To confirm the completeness of resection, a bilateral neck exploration was performed through the same incision, with identification of three normally sized parathyroid glands. CONCLUSIONS: Our experience suggests the utility of multimodality imaging procedures for the accurate preoperative localization of PAs, particularly when they are present in ectopic mediastinal locations. Such procedures, including the MIBI-SPECT-CT image fusion study, can be performed in a single day.

Scintigraphic imaging of the adrenal glands.

This article presents the well established scintigraphic imaging techniques of the adrenal glands. Both adrenocortical scintigraphy with [131]6beta-iodomethylnorcholesterol (NP-59) and adrenomedullary imaging with 131I or 123I-labelled metaiodobenzylguanidine (MIBG) as function-dependant imaging techniques provide functional metabolic information for lesion characterization. They enable the distinction between unilateral and bilateral adrenal lesions. Furthermore, they have the advantage of giving the possibility of a whole body evaluation with a single administration of the tracer without additional radiation dose. On the other hand, radiological imaging modalities provide excellent anatomical details which is essential for planning therapy. Both radiological and scintigraphic imaging methods of the adrenal glands are necessary and should, therefore, be considered complementary.