Amir Kurtaran

Vasoactive Intestinal Peptide-Receptor Imaging for the Localization of Intestinal Adenocarcinomas and Endocrine Tumors

Background Intestinal adenocarcinomas and various endocrine tumors express large numbers of high-affinity receptors for vasoactive intestinal peptide (VIP). We have evaluated the usefulness of scanning with VIP labeled with iodine-123 for tumor localization in patients with gastrointestinal tumors. Methods Radioiodinated VIP was purified by high-pressure liquid chromatography and administered as a single intravenous bolus injection (300 pmol [1 microgram]). Scanning with radiolabeled VIP was compared with computed tomography and scanning with somatostatin analogues in 79 patients with colorectal cancer, pancreatic carcinoma, gastric cancer, carcinoid tumor, or insulinoma. Results Visualization of gastrointestinal tumors and metastases was obtained with radiolabeled VIP. Binding of the labeled peptide by primary tumors and metastases was visible shortly after the injection and was still demonstrable at 24 hours. In patients with colorectal adenocarcinomas, primary or recurrent tumors were visualized in 10 ...

11C-Acetate Positron Emission Tomography Imaging and Image Fusion With Computed Tomography and Magnetic Resonance Imaging in Patients With Recurrent Prostate Cancer

PURPOSE To assess the clinical value of computed tomography (CT) and magnetic resonance imaging (MRI) image fusion with 11C-acetate (AC) positron emission tomography (PET) imaging for detection and exact location of clinically occult recurrences. PATIENTS AND METHODS Fifty prostate cancer patients with elevated/increasing serum prostate-specific antigen levels after radical therapy underwent whole-body AC PET. Uptake was initially interpreted as normal, abnormal, or equivocal. In case of abnormal or equivocal uptake, additional conventional imaging techniques, such as CT, MRI, and bone scans, were performed. To precisely define the anatomic location of abnormal uptake and to improve characterization of equivocal lesions, a software-assisted image fusion (CT-PET, MRI-PET) was performed and evaluated as site-by-site analysis of 51 abnormal (n = 37) or equivocal (n = 14) sites of all 50 patients. In 17 patients, additional histopathologic evaluation was available. RESULTS In five (10%), 13 (26%), and 32 (64%) of the 50 patients, AC PET studies demonstrated AC uptake judged as normal, equivocal, and abnormal, respectively. Image fusion changed characterization of equivocal lesions as normal in five (10%) of 51 sites and abnormal in nine (18%) of 51 sites. It precisely defined the anatomic location of abnormal uptake in 37 (73%) of 51 sites. AC PET findings did influence patient management in 14 (28%) of 50 patients. CONCLUSION Retrospective fusion of AC PET and CT/MRI is feasible and seems to be essential for final diagnosis. This is particularly true in patients with AC uptake in the prostate region.

FDG-PET in adrenocortical carcinoma.

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for follow-up.

Value of Peptide Receptor Scintigraphy Using 123I-Vasoactive Intestinal Peptide and 111In-DTPA-D-Phe1-Octreotide in 194 Carcinoid Patients: Vienna University Experience, 1993 to 1998

PURPOSE To report our experience with both (123)I-vasoactive intestinal peptide (VIP) and (111)In-DTPA-D-Phe(1)-octreotide for imaging to identify primary and metastatic tumor sites in carcinoid patients. PATIENTS AND METHODS One hundred ninety-four patients with a verified or clinically suspected diagnosis of a carcinoid tumor were injected with (111)In-DTPA-D-Phe(1)-OCT for imaging purposes, while 133 patients underwent scanning with both (123)I-VIP and (111)In-DTPA-D-Phe(1)-OCT in random order. Imaging results were compared with computed tomography scans, results of conventional ultrasound, endosonography, and endoscopy, and results of surgical exploration in case of inconclusive conventional imaging. RESULTS Primary or recurrent carcinoid tumors could be visualized with (111)In-DTPA-D-Phe(1)-OCT in 95 (91%) of 104 patients; metastatic sites were identified in 110 (95%) of 116 patients. In 11 (51%) of 21 patients with suggestive symptoms but without identified lesions by conventional imaging, focal tracer uptake located the carcinoid tumor. In addition, metastatic disease was demonstrated in three patients after resection. In a direct comparison in the 133 patients who underwent both imaging modalities, (111)In-DTPA-D-Phe(1)-OCT was found to be superior to (123)I-VIP, with 35 (93%) of 38 versus 32 (82%) of 38 scans being positive in primary or recurrent tumors, 58 (90%) of 65 versus 53 (82%) of 65 being positive in patients with metastatic sites, and seven (44%) of 16 versus four (25%) of 16 being positive in patients with symptoms but otherwise negative work-ups. Overall, additional lesions not seen on conventional imaging were imaged in 43 (41%) of 158 versus 25 (25%) of 103 scans with (111)In-DTPA-D-Phe(1)-OCT and (123)I-VIP, respectively. CONCLUSION Both peptide tracers have a high sensitivity for localizing tumor sites in patients with ascertained or suspected carcinoid tumors, with (111)In-DTPA-D-Phe(1)-OCT scintigraphy being more sensitive than (123)I-VIP receptor scanning. Both, however, had a higher diagnostic yield than conventional imaging, as verified by surgical intervention or long-term follow-up. The combination of both peptide receptor scans does not seem to further enhance diagnostic information.

Impact of localization studies on feasibility of minimally invasive parathyroidectomy in an endemic goiter region

BACKGROUND A localized single-gland disease is the basis for minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (PHPT). (99m)Tc sestamibi scanning (MIBI) and high-resolution Doppler ultrasonography (US) are well-established techniques used to localize enlarged parathyroid glands. Additionally, US enables physicians to diagnose subclinical thyroid abnormalities. The aim of this study was to optimize localization results, applying a combined interpretation of MIBI and US, and to analyze the influence of these results on the feasibility of MIP (endoscopic/video-assisted and open) in an endemic goiter region. STUDY DESIGN One hundred fifty consecutive patients with sporadic PHPT were prospectively subjected to MIBI and US to localize parathyroid lesions and to review the morphology of the thyroid gland. Bilateral cervical exploration was performed in all patients. The feasibility of MIP was calculated retrospectively on the basis of surgical findings and biochemical outcomes at least 12 months postoperatively (normocalcemia in 148 of 150 patients [99%]). RESULTS Forty-five percent of patients (67 of 148) would have been suitable for minimally invasive endoscopic or video-assisted parathyroid exploration. These procedures would have succeeded in 38% of patients (56 of 148). Sixty-four percent (94 of 148) would have been suitable for minimally invasive open parathyroidectomy, which would have succeeded in 55% (82 of 148 patients). CONCLUSIONS Not all patients are suitable for MIP. A combined interpretation of MIBI and US results is helpful in planning targeted exploration. In an endemic goiter region minimally invasive open parathyroidectomy is applicable in significantly more patients than is endoscopic and video-assisted MIP.

123I-vasoactive intestinal peptide (VIP) receptor scanning: Update of imaging results in patients with adenocarcinomas and endocrine tumors of the gastrointestinal tract

Recent data suggest that functional receptors (R) for vasoactive intestinal peptide (VIP) are expressed on various tumor cells. The high-level expression of VIPR on tumor cells provided the basis for the successful use of 123I-labeled VIP for the in vivo localization of intestinal adenocarcinomas and endocrine tumors. We here report an update of our imaging results using 123I-VIP (150-200 MBg/1 microgram/patient) in 169 patients. In patients with pancreatic adenocarcinomas without liver metastases, the primary/recurrent tumor was visualized in 16 of 18 patients (89%) and liver metastases were imaged in 15 of 16 patients. In 11 of 12 patients with colorectal adenocarcinomas, the primary/recurrent tumor (92%) was imaged by 123I-VIP. Also, in 21 of 25 patients, liver metastases (84%); in 3 of 6 patients, lung metastases (50%); and in 4 of 5 patients, lymph-node metastases (80%) were imaged by 123I-VIP. In 10 of 10 patients with gastric adenocarcinomas, the primary/recurrent tumor; in 3 of 4 patients, liver metastases; and in 2 of 2 patients, lymph-node metastases were visualized by 123I-VIP. 123I-VIP localized primary intestinal carcinoid tumors in 15 of 17 patients (88%) and 8 of 10 primary insulinomas (80%). We conclude that the 123I-VIPR scintigraphy localizes intestinal adenocarcinomas and endocrine tumors as well as metastatic tumor sites.

Post-treatment imaging of liver tumours.

Abstract In the past few years, great improvements have been made to achieve local tumour control of primary liver malignancies and liver metastases. For hepatocellular carcinoma (HCC), transarterial chemoembolisation (TACE) and tumour ablation techniques, including percutaneous ethanol injection (PEI), radiofrequency ablation (RF), and laser-induced interstitial thermotherapy (LITT) have been developed. For colorectal liver metastases, surgery is still the standard technique in localised disease, although percutaneous RF ablation has gained considerable acceptance. In patients with widespread disease, chemotherapy with new drugs offers improved survival. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are the modalities of choice to evaluate treatment response. The present review demonstrates imaging findings of complete and incomplete tumour control after intervention as well as the imaging spectrum of complications. Imaging guidelines according to the World Health Organization and Response Evaluation Criteria In Solid Tumors (RECIST) for assessment of chemotherapy response are presented.

In vitro and in vivo studies of three radiolabelled somatostatin analogues:123I-Octreotide (OCT),123I-Tyr-3-OCT and111In-TIRA-d-Phe-1-OCT

Scintigraphy with long-acting somatostatin (SST) analogues may be useful for the localization of tumours expressing receptors (R) for SST. In this study we have analysed the in vitro and in vivo binding properties of three SST analogues,123I-octreotide (OCT),123I-Tyr-3-OCT and111In-DTPA-d-Phe-l-OCT. In vitro binding studies performed with a variety of primary tumours (n=48) as well as with several tumour cell lines (A431, HT29, PANC1, COLO320, HMC1, KU812) indicated significant in vitro binding of these three radiolabelled SST analogues to two subpopulations of SSTR, high (Kd 0.2–2.0 nM) and low (Kd 5–15 nM) affinity ones. The number of SSTR on tumour cells was at least a 1000-fold higher as compared with normal peripheral blood cells. Comparative scintigraphic studies using123I-OCT and/or123I-Tyr-3-OCT and/or111In-DTPA-d-Phe-1-OCT were performed in 21 patients with histologically verified intestinal carcinoid tumours. Corresponding scintigraphic results were obtained in 18 of 21 patients investigated with two different SSTR ligands, either123I-OCT/123I-Tyr-3-OCT (four of five),123I-OCT/111In-DTPA-d-Phe-1-OCT (eight of nine), or123I-Tyr-3-OCT/111In-DTPA-d-Phe-1-OCT (six of seven). We conclude that various tumours express high amounts of SSTR which are recognized by three radiolabelled SST analogues:123I-OCT,123I-Tyr-3-OCT and111In-DTPA-d-Phe-1-OCT. Differences between these SST analogues in their in vitro binding and/or in vivo scanning properties are observed in a minority of patients. Thus, the labelling of OCT with iodine may be an alternative approach for those nuclear medicine departments for which111In-DTPA-d-Phe-1-OCT is not easily available, or is too expensive.

‘Suppressed’ Double Adenoma – A Rare Pitfall in Minimally Invasive Parathyroidectomy

Since the introduction of a quick intraoperative parathyroid hormone (QPTH) assay, complete removal of hyperfunctioning parathyroid tissue can be proven during surgery. We report on a scintigraphically and biochemically documented patient with persistent primary hyperparathyroidism (PHPT) caused by suppressed hyperfunctioning parathyroid tissue. A left lower enlarged parathyroid gland was resected by minimally invasive open parathyroidectomy. QPTH measurements confirmed complete resection of hyperfunctioning tissue and histology showed a tumorous enlarged left lower parathyroid gland. The patient was normocalcemic until 1 month after surgery, when serum calcium increased again. A MIBI scan 6 months after surgery showed no evidence of hyperfunctioning parathyroid tissue. After an increase of PTH, a third MIBI scan another 3 months later was performed. Increased tracer uptake behind the lower pole of the right thyroid lobe was seen and confirmed by ultrasonography. Another tumorous enlarged parathyroid gland was removed. These findings support the hypothesis that smaller yet abnormal parathyroid glands can be suppressed and may become hypersecretory if left in situ after surgical removal of the larger gland.

Different Response to the Long-Acting Somatostatin Analogues Lanreotide and Octreotide in a Patient with a Malignant Carcinoid

Introduction: Somatostatin (SST) analogues are cornerstones in the symptomatic management of patients suffering from carcinoid tumors, and antiproliferative activity has also been reported for these agents. The most commonly applied SST analogues are octreotide (OCT) and lanreotide (LAN), which are both available in a slow release formulation. To the current knowledge, both OCT and LAN are thought to be equally effective for the management of various disorders. We report the case of a patient with a disseminated carcinoid, who progressed during dose-intensified treatment with slow-release LAN in combination with interferon-α, but developed a pronounced response after treatment was switched to the application of a depot formulation of OCT. Case Report: A 46-year-old woman was admitted to our department for the evaluation of persistent flushing, diarrhea and dyspnea. After a diagnosis of metastatic carcinoid had been established, treatment with LAN (30 mg i.m. every 10 days) along with interferon-α 3 × 5 MU/week was initiated. In spite of successful blocking of tumoral SST receptors as judged by SST receptor scintigraphy and subjective improvement of symptoms, the patient had progressive disease. As she refused chemotherapy, treatment was switched to a depot formulation of OCT (20 mg i.m. every 4 weeks), resulting both in a disappearance of symptoms as well as tumor regression as seen on CT scanning. Conclusion: To our knowledge, this is the first case demonstrating both a symptomatic as well as objective response to OCT following progression during therapy with LAN in a patient with a carcinoid tumor. Our results suggest that refractoriness to treatment including a long-acting SST analogue does not automatically imply resistance to a related agent and should alert clinicians to the potential of non-cross-resistance between SST analogues in neuroendocrine malignancies.