Somatostatin receptor scintigraphy of non-neuroendocrine malignancies with 111In-pentetreotide.

In-111 pentetreotide is a new radiolabelled [OctreoScan 111, Mallinckrodt Medical BV, Petten] somatostatin analog with high affinity to somatostatin receptors (SR). introduced for the in vivo imaging of SR positive tissues. In an attempt to evaluate its clinical usefulness for tissue characterization in malignancies without neuroendocrine expression in parallel with histological and radiological examinations, specific scintigraphy was performed on brain (6 cases), thyroid (6 cases) and breast (9 cases) tumors, and in lymphomas (9 cases) and melanomas (6 cases). A dose of 111MBq of In-111 pentetreotide was injected i.v. to each patient and scintimages at 6 and 22 hours (for comparison) p.i. were obtained. The primary lesion of the breast cancer population was imaged in all 9 cases as well as all the palpable axillary nodes in 4 cases. Three women with impalpable axillary lymph nodes scanned negative but had a positive biopsy. Both meningiomas were positive for SR scans: positive results were also obtained for the high grade astrocytoma and the craniopharyngioma: Two out of 6 patients with papillary thyroid cancer showed a marked radiotracer accumulation. Scintigraphy in all 5 lymphomas was positive for SR but did not detect the Tc-99m sulphur microcolloid [Lymphoscint, Solco, Basel, Suitzerland] imaged lymph nodes in 5 melanomectomized patients. When judging the imaging results of these non-neuroendocrine malignancies definite conclusions should not be drawn since the number of studied cases polymorph, was small for every cancer histotype; nevertheless SR scintigraphy does not seem to be reliable for tumor staging in non-neuroendocrine malignancies, but is more suitable for a tissue characterization and monitoring changes of SR expression during and after therapy.

Comparison of In-111 pentetreotide, Tc-99m (V)DMSA and I-123 mlBG scintimaging in neural crest tumors.

Three radiolabelled substances, 111In-pentetreotide, 99mTc-(V)DMSA and 123I-MIBG with different kinetics but similar tumor seeking behavior, were i.v. injected to assess and correlate their clinical value in metastatic malignant pheochromocytomas (4 patients), stage III and IV neuroblastomas (7 patients) and medullary thyroid carcinomas (6 patients). All II pheochromocytoma/neuroblastoma patients received i.v. a dose of III MBq (3 mCi) of 123I-MIBG and 185 MBq (5 mCi) of 111In-pentetreotide, within approximately weeks each other. Furthermore, in 4 of these patients as well as in all medullary thyroid carcinoma patients 111 MBq (3 mCi) of 99mTc-(V)DMSA were applied i.v. I week prior to the pentetreotide/mlBG scans. Four patients (malignant pheochromocytoma) with a total of 7 foci showing MIBG accumulation had 3 sites with pentetreotide and 1 site with (V)DMSA uptake, while in 7 patients (neuroblastora) with 15 foci showing MIBG accumulation 10 sites had detectable pentetreotide and 3 sites detectable (V)DMSA. Of the three radiotracers, 111In-pentetreotide used for somatostatin receptor identification holds promise mainly in cases where foci imaged with 123I-MIBG are negative. 111In-pentetreotide is unlikely to replace 123I-MIBG as a first-line routine diagnostic scintigraphic modality; compared to pentetreotide or MIBG, (V)DMSA seems to be highly sensitive only in medullary thyroid carcinomas.

99mTc-antigranulocyte bone marrow scintigraphy of breast and prostate skeletal metastases.

Although bone scintigraphy using Tc-99m labelled diphosphonates is a highly sensitive modality for the detection of of the extent of secondary skeletal malignancies, it is often not sufficient since possible bone marrow participation cannot be imaged We make a preliminary report on the usefulness of bone marrow immunoscintigraphy in the follow-up of patients with skeletal metastases due to breast and prostate cancer in parallel with the interpretation of conventional Tc-99m MDP bone scans. Approximately 7 to 9 months after radionuclide therapy both Tc-99m MDP [Hellenic Nuclear Research Center "Democritos". Aghia Paraskevi, Attikil and Tc-99m Anti-Granulocyte BW 250/183 [CIS Bio International, Gif sur Yvette, France] bone scans were performed on 2 prostate cancer patients and 5 women with breast cancer with disseminated bone metastases. Bone scans preceded bone marrow scans. Bone marrow defects were concordant with cortical scans in 4 cases, while they were larger in 4 sites compared to -MDP scan. Four sites in the ribs, shown on -MDP scan could not be detected on antigranulocyte scans. Bone cortex and marrow combined imaging of osseous metastases using different radiotracers increases the information on the real extent of skeletal involvement; the scintigraphic data obtained are valuable for the further decision making for the best possible management of unexpected myelosuppressive side effects as well as the follow-up of the treated cancer patients.

Two phase scintigraphic mapping of lymphatic drainage in cutaneous melanoma using 99mTc-sulfur microcolloid/99mTc antimelanoma antibody.

The purpose of lymphoscintigraphy in patients with melanoma before surgery is to image the lymphatic drainage net and particularly to detect the sentinel node; the purpose of immunolymphoscintigraphy after surgery is to map the lymphatic drainage and to detect a possible spead of the malignancy towards the lymph nodes surrounding the surgical field or more distal regions. The aim of the present study was to assess the sensitivity of a two-phase procedure with Tc-99m-Iabelled agents for exploring possible spread of melanoma after thorough resection of the primary lesion. Seven melanomectomized patients were enrolled into the study. The melanomas were situated on the head, back, arm and buttock of these patients. Intracutaneous lymphoscintigraphy with Tc-99m sulphur microcolloid [Lymphoscint, Solco, Basel, Switzerland] and i.v. immunoscrintigraphy with Tc-99m-antimelanoma antibody [Tecnemab-K-I, Sorin Biomedica Spa, Saluggia, Italy] at a dosage of 55 MBq and 740 MBq respectively, were performed in 13 patients to define possible infiltration of lymph nodes after surgery with a time interval of 1 week between the two examinations. Tc-99s sulphur microcolloid preceded the Tc-99m anti-melanoma antibody scan. The scintigrams were evaluated by three experienced nuclear physicians. The method detected 3 out of 16 suspicious nodes as malignant. Combined two-phase technique improves the diagnostic and staging accuracy of cutaneous melanoma affected population and appears extremely useful in the surgical confrontation of the lymphatic spead.

Receptor scintigraphy of non-neuroendocrine cancers with In-111 pentetreotide.

Somatostatin receptors (SR) are surface markers characterizing not only APUDomas associated with neuroendocrine identities but also malignancies without neuroendocrine expression. Recently, the somatostatin analog pentetreotide was labeled with In-111 (OctreoScan 111, Mallinckrodt Medical BV, Petten, Holland) and introduced for the in vivo visualization in man of SR-positive tissues. In the present report, SR-specific scintigraphy is evaluated as a clinical tool for tissue characterization in correlation with histological and radiological examinations. Scintigraphy was focused and performed in cancer types without neuroendocrine tissue expression such as brain (n = 6) and breast tumors (n = 9) and lymphomas (n = 5). Scintigraphy was performed for comparison at 6 and 22 h after i.v. application of 111 MBq (3 mCi) of In-111-Pentetreotide. In the breast cancer group, the primary tumor was visualized in all 9 women as well as in all 4 cases with palpable axillary lymph nodes. Three women with a negative axillary node scan and impalpable nodes had positive biopsy. In two cases, mediastinal lymph node involvement was observed. So far the role of SR-positive breast cancer (BC) scans remains unknown. It is tempting to speculate that in resected women who are histologically and scintigraphically SR positive, it might be of value in the early detection of symptom-free recurrences. High densities of SR were present within both meningiomas, the high-grade astrocytoma and the craniopharyngioma. Differentiation of low- and high-grade astrocytomas could not be successfully achieved because both grades showed intense radioactivity uptake, even though high-grade tumors lack SR. The latter might be due to the damaged blood-brain barrier and the poor radioactivity washout observed in high-grade astrocytomas. All five lymphomas could be detected due to the presence of activated lymphocytes and macrophages that express SR at a sufficient density. In conclusion, SR scintigraphy in non-neuroendocrine malignancies does not seem to be reliable for an initial tumor staging but rather more suitable for a tissue characterization and extremely useful for monitoring changes of SR expression after treatment.

Radionuclide visualization of acute occlusive and nonocclusive intestinal ischemia.

A noninvasive radionuclide technique to visualize ischemic small intestine was evaluated. Vascular ligation of 20-30 cm ileum was done in rabbits. After induction of ischemia, technetium (99mTc) methylene diphosphonate (TMDP) was injected IV at intervals up to 24 hours. Images were recorded 1 and 3 hours after injection of radioisotope and showed preferential (9:1) uptake by ischemic bowel. Positive scans were present in all animals up to 4 hours and in 75% at 10-12 hours, but in none 24 hours after induction of ischemia. Nonocclusive intestinal ischemia was simulated in 4 dogs by infusing norepinephrine into a jejunal mesenteric arterial branch. After 1 hour, an IV bolus of TMDP was injected and images recorded at intervals up to 3 hours. Selective uptake of isotope by the ischemic segment was observed in all animals. Angiography confirmed that isotope uptake was confined to the infused segment. These studies show that occlusive intestinal ischemia can be detected, by radionuclide imaging up to 12 hours, and nonocclusive (low flow) ischemia for at least 4 hours, after onset.