Sentinel node biopsy in melanoma using technetium-99m rhenium colloid: the London experience.

Nodal metastases in patients with melanoma identify a reduction of survival by 50%; however, elective lymph node dissection (ELND) has not been shown clearly to improve survival. Morton's technique of sentinel node biopsy, using preoperative lymphoscintigraphy and intraoperative blue dye, addresses elegantly the controversy regarding ELND. Sentinel node biopsy has been shown to stage the patient accurately because metastases from melanoma follow an orderly progression from the sentinel node to the remainder of the basin. Fifty-six consecutive patients with American Joint Committee on Cancer stage 1b or 2 melanoma seen at the London Health Sciences Center between July 1998 and January 2000 were enrolled prospectively to undergo sentinel node biopsy. Preoperative lymphoscintigraphy was conducted in the nuclear medicine department. A total of 10 to 15 MBq (0.27-0.41 mCi) of technetium 99m (99mTc) rhenium colloid or filtered sulfur colloid was injected intradermally around the biopsy scar. Images were obtained to localize all draining nodal basins. The location of the sentinel node was marked on the skin. The patient was taken to the operating room and anesthetized. Isosulfan blue dye was injected intradermally around the biopsy scar. A hand-held gamma probe was used intraoperatively as a guide to the first draining node. Blue-stained lymphatic channels aided in the dissection. Sentinel node localization was successful in 55 of 56 patients, for an overall success rate of 98%. Preoperative lymphoscintigraphy identified a sentinel node in an unpredictable location in 32% of patients. On average, 2.3 sentinel nodes per patient were identified on the initial scan, and 2.2 sentinel nodes per patient were recovered at surgery. Both 99mTc rhenium and filtered sulfur colloid showed no substantial differences in tracer uptake and retention in the sentinel node. Twelve patients had a positive sentinel node on routine histology, and 11 patients subsequently underwent completion lymphadenectomy. The mean thickness of the primary melanoma in the 12 patients with positive sentinel nodes was 3.7 mm compared with a mean tumor thickness of 1.8 mm in the remaining 41 patients with negative biopsies (p = 0.0003). Two patients experienced recurrence in a regional basin after negative pathological evaluation of the sentinel node. Reverse transcription-polymerase chain reaction analysis of both of these patients was positive. Two patients are alive with metastatic disease and 54 patients are alive without disease, with a mean follow-up of 1 year (range, 2-24 months). Complications occurred at a substantially higher rate (45%) after completion lymphadenectomy than after sentinel node biopsy alone (9%). Sentinel node biopsy is a feasible technique with a high success rate (98%), but it requires a multidisciplinary approach. This study validates the clinical usefulness of 99mTc rhenium colloid for lymphoscintigraphy.

Amino and iodotamoxifens: synthesis, estrogen receptor affinity and biodistribution.

Both geometrical isomers (E and Z) of an aminotamoxifen (2) have been prepared as precursors of the corresponding E and Z iodotamoxifens (1). The ability of E and Z-1 and 2 to compete with [3H]estradiol for estrogen receptors in rat uterine cytosol was measured relative to Z-tamoxifen and estradiol. The four tamoxifen derivatives showed affinities ranging from 50% to 1600% of that of tamoxifen. Under the same conditions, tamoxifen's relative binding affinity was 0.2% of that of estradiol. Preparative routes to the radioiodo-tamoxifens, [131I]-E and Z-1, were also developed and provided approximately 100 MBq of 'no carrier added' material in 40-60% radiochemical yield. Study of the biodistribution of these radioligands in tumor-bearing mice demonstrated significant radioactivity in the tumors and in the uterus. For [131I]-E-1, target to background ratios reached 28 for uterus/blood and 10 for tumor/blood; corresponding optimum ratios for [131I]-Z-1 were 10 and 5. A washout study using estradiol indicated selective uptake in the uterus of Swiss white mice. However, tumor uptake and image contrast in humans following intravenous administration of either [131I]-E or Z-1 were insufficient to allow diagnostic use of the radioiodotamoxifens.

Hepatic uptake of technetium-99m HM-PAO in a fetus.

The normal biodistribution of technetium-99m HM-PAO ([99mTc]HM-PAO) includes significant uptake in the brain, liver, and kidneys. A pregnant patient studied with [99mTc] HM-PAO to confirm brain death provided an opportunity to examine the transplacental distribution of this radio-pharmaceutical in the unborn fetus. Uptake in the fetus after transplacental delivery is almost exclusively hepatic with a small amount of biliary excretion.

Cerebral perfusion imaging with technetium-99m HM-PAO in brain death and severe central nervous system injury.

We performed 38 cerebral perfusion studies in 33 patients with brain death or with severe central nervous system injury using technetium-99m hexamethyl-propyleneamine oxime [( 99mTc]HM-PAO). Uptake by the cerebrum and/or cerebellium was present in all patients who were not clinically brain dead (ten studies) although the study was often abnormal. In those patients who were brain dead, 16/17 studies demonstrated no uptake in either the cerebrum or cerebellum. In patients suspected of brain death, but who had conditions interfering with the diagnosis the test demonstrated no uptake in 9/11 studies, confirming brain death. A radionuclide angiogram (RNA) of the head was also performed in 33/38 studies and showed complete agreement with the [99mTc]HM-PAO uptake, except in one case. We conclude that cerebral perfusion imaging with [99mTc]HM-PAO is a simple, noninvasive and reliable test to confirm brain death. By comparison with conventional technetium agents, [99mTc]HM-PAO is not dependent on the quality of the bolus injection, is easier to interpret and allows evaluation of posterior fossa blood flow.

Preparation and evaluation of radioiodinated (iodophenyl)cholines and their morpholinium and piperidinium analogues as myocardial perfusion imaging agents.

A series of nine radioiodinated quaternary ammonium salts related to phenylcholine were synthesized, characterized, and radiolabeled by exchange. These compounds were evaluated as myocardial perfusion imaging agents in mice, pigs, and humans. Mice biodistribution studies showed that five of the nine compounds were taken up in the heart to the same extent as 201Tl+ at 5 min. At 60 min myocardial retention was significantly better than 201Tl+ for six of the compounds. Several of the compounds showed more favorable heart/blood and heart/liver ratios when compared to 201Tl+. Evaluation of three of the more promising compounds in pigs and humans however revealed no selective myocardial uptake.

Radioiodinated peanut lectin: a potential radiopharmaceutical for immunodetection of carcinoma expressing the T antigen.

The Thomsen-Friedenreich (T) antigen, beta-D-Gal-(1 leads to 3)-alpha-D-GalNAc, is exposed in reactive form on many human adenocarcinomata, but not on corresponding benign tissues. Peanut lectin (PNA) has a strong binding affinity for the T antigen and reportedly binds preferentially to certain malignant tissues. We investigated the potential of radiolabelled PNA as a tumour localising agent in an animal model system using a mouse lymphoma (RI) shown to bind fluorescein-labelled PNA in vitro. The radioiodinated lectin showed good tumour localization and rapid blood clearance. Clear images of tumours were obtained, in serial scintigraphic imaging, by 24 and 48 h. No blood background subtraction was necessary. Biodistribution studies revealed tumour to blood ratios in mice were 6:1 (at 24 h) and 17:1 (at 48 h), and tumour to muscle ratios were 34:1 (at 24 h) and 40:1 (at 48 h). Rapid in vivo breakdown of 125I-PNA led to some localization of free iodide in the kidneys, stomach, thyroid and salivary glands.